Document:

Exhibit 10.2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

16. TABLE OF   CONTENTS CONTRACTING OFFICER WILL COMPLETE ITEM 17 OR 18 AS APPLICABLE NSN   7540-01-152-8069 PREVIOUS EDITION UNUSABLE 26-107 Computer Generated STANDARD   FORM 26 (REV. 4-85) Prescribed by GSA, FAR (48 CFR) 53.214(a) 123269097 v2 17.   CONTRACTOR’S NEGOTIATED AGREEMENT (Contractor is 18. AWARD (Contractor is not   required to sign this document.) Your offer on required to sign this document   and return 2 copies to issuing office.) Contractor agrees to furnish and   deliver all items or perform all the services set forth or otherwise   identified above and on any continuation sheets for the consideration stated   herein. The rights and obligations of the parties to this contract shall be   subject to and governed by the following documents: (a) this award/contract,   (b) the solicitation, if any, and (c) such provisions, representations,   certifications, and specifications, as are attached or incorporated by   reference herein. (Attachments are listed herein.) Solicitation Number ,   including the additions or changes made by you which additions or changes are   set forth in full above, is hereby accepted as to the terms listed above and   on any continuation sheets. This award consummates the contract which   consists of the following documents: (a) the Government’s solicitation and   your offer, and (b) this award/contract. No further contractual document is   necessary. 19A. NAME AND TITLE OF SIGNER (Type or print) [***] [***] 20A.   NAME OF CONTRACTING OFFICER [***] 19B. NAME OF CONTRACTOR /s/ [***]   (Signature of person authorized to sign) 19C. DATE SIGNED 13/11 ‘09 20B.   UNITED STATES OF AMERICA BY /s/ [***] (Signature of Contracting Officer) 20C.   DATE SIGNED November 16, 2009 () SEC. DESCRIPTION PAGE(S) () SEC. DESCRIPTION   PAGE(S) PART I - THE SCHEDULE PART II - CONTRACT CLAUSES A   SOLICITATION/CONTRACT FORM 1 I CONTRACT CLAUSES 20 B SUPPLIES OR SERVICES AND   PRICE/COST 2 PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH. C   DESCRIPTION/SPECS./WORK STATEMENT 4 J LIST OF ATTACHMENTS 24 D PACKAGING AND   MARKING 8 PART IV - REPRESENTATIONS AND INSTRUCTIONS E INSPECTION AND   ACCEPTANCE 9 K REPRESENTATIONS, CERTIFICATIONS AND OTHER STATEMENTS OF   OFFERORS 25 F DELIVERIES OR PERFORMANCE 10 G CONTRACT ADMINISTRATION DATA 11   L INSTRS., CONDS., AND NOTICES TO OFFERORS N/A H SPECIAL CONTRACT   REQUIREMENTS 14 M EVALUATION FACTORS FOR AWARD N/A AWARD/CONTRACT 1. THIS   CONTRACT IS A RATED ORDER UNDER DPAS (15 CFR 350) RATING N/A PAGEOFPAGES 1 25   2. CONTRACT (Proc. Inst. Ident.) NO HHSO100201000011C 3. EFFECTIVE DATE See   Block 20C 4. REQUISITION/PURCHASE REQUEST/PROJECT NO N/A 5. ISSUED BYCODE N/A   6. ADMINISTERED BY (If other than Item 6)CODE N/A HHS/OS/ASPR/BARDA 330   INDEPENDENCE AVE S.W., RM G640 WASHINGTON, D.C. 20201 See Block 5 7. NAME AND   ADDRESS OF CONTRACTOR (No., street, county, state and ZIP Code) BAVARIAN   NORDIC A/S Hejreskovvej 10A 3490 Kvistgård Denmark 8. DELIVERY FOB   ORIGINOTHER (See below) 9. DISCOUNT FOR PROMPT PAYMENT N/A 10. SUBMIT   INVOICES ADDRESS SHOWN IN ITEM See Section G FACILITY CODEN/A 11. SHIP   TO/MARK FORCODE N/A 12. PAYMENT WILL BE MADE BYCODE N/A See Block 5 See Block   5 13. AUTHORITY FOR USING OTHER FULL AND OPEN COMPETITION:  10 U.S.C. 2304(c)() 41 U.S.C. 253(c)() 14.   ACCOUNTING AND APPROPRIATION DATA 15A. ITEM NO. 15B. SUPPLIES/SERVICES 15C.   QUANTITY 15D. UNIT 15E. UNIT PRICE 15F. AMOUNT See Section B $[***] 15G.   TOTAL AMOUNT OF CONTRACT $[***] 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Contract Number HHSO100201000011C

Bavarian Nordic A/S

 

SECTION B—SUPPLIES OR SERVICES AND PRICES/COSTS

 

B.1.              BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

 

The Contractor shall supply the necessary supplies and services to produce and validate a freeze-dried IMVAMUNE Final Drug Product (FDP) to generate sufficient data to support the use of this smallpox vaccine in a declared emergency.

 

B.2                 PRICES/COSTS

 

A.                        CONTRACT LINE ITEM NUMBERS (CLIN’s)

 

1.                          BASE CONTRACT

 

	
CLIN’s
    	
 
    	
SUPPLIES/SERVICES
    	
 
    	
EST. COST
    	
 
    	
FIXED
   FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0001
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
													

 

2.                          CONTRACT OPTIONS

 

If the Government exercises its option pursuant to Section H, Paragraph H.13 of this contract, the Government’s total obligation represented by the sum of the estimated cost plus fixed fee may be increased as shown in the below CLIN’s 0002 through 0005, in consideration for completion of the work described in the individual CLIN’s and in accordance with the Statement of Work:

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0002
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0003
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0004
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0005
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    

 

B.3.              PROVISIONS APPLICABLE TO DIRECT COSTS

 

This paragraph applies only to the cost reimbursable CLIN’s.  Notwithstanding the clauses, ALLOWABLE COST AND PAYMENT and FIXED FEE, incorporated in this contract, unless authorized in writing by the Contracting Officer, the cost of the following items or activities shall be unallowable as direct costs:                                               1) Acquisition, by purchase or lease, of any interest in real property; 2) Special rearrangement or alteration of facilities; 3) Purchase or lease of any item of general purpose office furniture or office equipment regardless of dollar value; 4) Subcontract Costs; and 5) Accountable Government Property.

 

B.4.              ADVANCE UNDERSTANDINGS

 

1)             Man-in-Plant

 

With 7 days advance notice to the Contractor, the Government may place a man-in-plant in the Contractor’s facility.  The man-in-plant is restricted to observing, verifying, and surveying the contractor’s performance under this contract.

 

2)             Security Plan

 

The Contractor agrees to provide an updated Security Plan, if requested by the Project Officer, and within fifteen (15) working days after receipt of the request.  The Contractor shall only produce and store product in a secure facility.  In addition, all work performed under this contract shall be in accordance with the implemented security plan- ensuring the security of vaccine production.

 

3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

SECTION C - DESCRIPTION/SPECIFICATIONS

 

C.1.  STATEMENT OF WORK

 

A.            Independently, and not as an agent of the USG, the Contractor shall furnish all the necessary services, qualified personnel, materials, supplies, equipment, facilities, transportation and travel not otherwise provided by the USG as required to perform the specific Contractor Defined Milestones detailed below for the base contract, as further specified in the Work Statement, which is incorporated into this contract as Attachment #1 under SECTION J.

 

	
Description
    	
 
    	
Statement of Work Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

B.            CONTRACT OPTIONS

 

The Government may exercise any of the four options for the continuation of requirements as set forth in the following Contractor Defined Milestones.  Exercise of each option also extends the contract’s period of performance by twelve months.

 

	
Description
    	
 
    	
Statement of Work Section Number
    
	
Option #1
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
 
    	
 
    	
 
    
	
Option #2
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
 
    	
 
    	
 
    
	
Option #3
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    
	
 
    	
 
    	
 
    
	
Option #4
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    

 

C.            The Government reserves the right to modify the milestones, progress, schedule, budget, or product to add or delete products, process, or schedule as the need may arise.  Because of the nature of this research and development contract, and the complexities inherent in this and prior programs, at designated milestones the Government will evaluate whether work should be redirected, removed, or whether schedule or budget adjustments should be made.  In any event, the Government reserves the right to change product, process, schedule or event, and to add or delete part or all of these elements as the need arises.

 

4

 

D.            MEETINGS AND CONFERENCES

 

The Contractor shall participate in regular meetings to coordinate and oversee the contract effort as directed by the Contracting and Project Officers.  Such meetings may include, but are not limited to, meeting of all Contractors and subcontractors to discuss clinical manufacturing progress, product development, product assay development, scale up manufacturing development, clinical sample assays development, pre clinical/clinical study designs and regulatory issues; meetings with individual contractors and other HHS officials to discuss the technical, regulatory, and ethical aspects of the program; and meeting with technical consultants to discuss technical data provided by the Contractor.

 

Monthly teleconferences between the Contractor and subcontractors and BARDA shall be held to review technical progress.  BARDA reserves the right to request more frequent teleconferences and face-to-face meetings depending on the criticality and nature of the work being performed.  The first reporting period consists of the first full month of performance plus any fractional part of the initial month.  Thereafter, the reporting period shall consist of each calendar month.  During these calls the Contractor’s Principal Investigator will discuss the activities during the reporting period, any problems that have arisen and the activities planned for the ensuing reporting period.  The Contractor will receive feedback from BARDA on contract performance, and will have an opportunity to respond and provide recommendations/ remediation plan during the execution of the contract.

 

1.              Regulatory and Quality Management:

 

FDA Submissions and meetings:

 

(a)         The contractor shall forward the initial draft minutes and final draft minutes of any formal meeting with the FDA to BARDA.

(b)         The contractor shall forward the final draft minutes of any informal meeting with the FDA to BARDA.

(c)          The contractor shall forward the dates and times of any meeting with the FDA to BARDA and make arrangements for appropriate BARDA staff to attend FDA meetings.

(d)         The contractor shall provide BARDA the opportunity to review and comment upon any documents to be submitted to the FDA.  The contractor shall provide BARDA with five (5) business days in which to review and provide comments back to the contractor.

(e)          The contractor shall forward Standard Operating Procedures (upon request from Project Officer/Contracting Officer).

(f)           The contractor shall provide upon request animal study and/or other technology packages developed under this contract. Packages shall include complete protocols and critical reagents for animal models developed and/or improved with contract funding.

(g)          The contractor shall provide upon request raw data and/or specific analysis of data generated with USG funds.

 

2.              Audits / Site Visits:

 

FDA Audits

 

Within thirty (30) calendar days of an FDA audit of Contractor or subcontractor facilities, the Contractor shall provide copies of the audit findings, final report, and a plan for addressing areas of nonconformance to FDA regulations and guidance for GLP, GMP or GCP guidelines as identified in the final audit report.

 

BARDA Audits

 

The United States Government (USG) reserves the right to conduct an audit of the Contractor with 48 hours notice. The USG reserves the right to accompany the Contractor on routine and for-cause site-visits/audits of subcontractors.  At the discretion of the USG and independent of testing conducted by the Contractor, BARDA reserves the right to conduct site visits/audits and collect samples of product held by the Contractor and subcontractors.

 

C.2.  REPORTING REQUIREMENTS AND DELIVERABLES

 

1)                         Technical Progress Reports

 

On the fifteenth (15) day of each month for the previous calendar month, the contractor shall submit to the Project Officer and the Contracting Officer a Technical Progress Report.  The frequency of Technical Progress Reporting will be determined by

 

5

 

the Contracting Officer and Project Officer during negotiations of the contract.  The format and type of Technical Progress Report and Executive Summary will be provided by the Project Officer.  The technical Progress Reports will include project timelines and milestones summaries of product manufacturing, testing, and clinical evaluation.  A Technical Progress Report will not be required for the period when the Final Report is due.  The Contractor shall submit one copy of the Technical Progress Report electronically via e-mail.  Any attachments to the e-mail report shall be submitted in Microsoft Word, Microsoft Excel, Microsoft Project, and/or Adobe Acrobat PDF files.  Such reports shall include the following specific information:

 

(a)         Title page containing:  Technical Progress Report, the contract number and title, the period of performance or milestone being reported, the contractor’s name, address, and other contact information, the author(s), and the date of submission;

(b)         Introduction/Background: An introduction covering the purpose and scope of the contract effort;

(c)          Progress:  The report shall detail, document and summarize the results of work performed, test results, milestones achieved during the period covered and cumulative milestones achieved.  Also to be included is a summary of work planned for the next two (2) reporting periods on a rolling basis;

(d)         Issues:  Issues resolved, new issues and outstanding issues are enumerated with options and recommendation for resolution.  An explanation of any difference between planned progress and actual progress, why the differences have occurred, and, if progress activity is delinquent, then what corrective steps are planned.  Revised timelines are provided.

(e)          Invoices:  Summary of any invoices submitted during the reporting period.

(f)           Action Items:  Summary table of activities or tasks to be accomplished by certain date and by whom.

(g)          Distribution list:  A list of persons receiving the Technical Report

(h)         Attachments:  Results on the project are provided as attachments

 

2)             The Executive Summary, which shall accompany each Technical Progress Report, will be formatted in Microsoft Power Point presentations and include the following:

 

(a)         Title page containing Executive Title, the contract number and title, the period of performance or milestone being reported, the contractor’s name and the date of submission;

(b)         Project Progress presented as milestone events, test results, tasks, and other activities achieved during the reporting period as talking point bullets;

(c)          Project issues presented headings and each item as a talking point bullet.

 

3)             Final Report: By the expiration date of the contract, the Contractor shall submit a comprehensive Final Report that shall detail, document, and summarize the results of the entire contract work.  The report shall explain comprehensively the results achieved.  A draft Final Report will be submitted to the Project and Contracting Officers for review and comments, then the Final Report original, four copies, and an electronic file shall be submitted to the Project and Contracting Officers for distribution to the Program office.

 

4)             Updated Integrated Product Development Plan (IPDP)

 

Within fourteen (14) days of the effective date of the BAA award, the Contractor shall submit an updated IPDP which shall be approved by the Project Officer and the Contracting Officer prior to initiation of any activities related to their implementation.

 

During the course of contract performance, in response to a need to change the IPDP, the Contractor shall submit a Deviation Report.  This report shall request a change in the agreed-upon Plan and timelines.  This report shall include:

 

(a)         Discussion of the justification/rationale for the proposed change.

(b)         Options for addressing the needed changes from the approved timelines, including a cost-benefit analysis of each option.

(c)          Recommendations for the preferred option that includes a full analysis and discussion of the effect of the change on the entire product development program, timelines, and budget.

 

The Contractor shall carry out activities within the contract Statement of Work only as requested and approved by the Contracting Officer, and may not conduct work on the contract without prior approval from the Contracting Officer, including initiating work that deviates from the agreed-upon IPDP.

 

5)             Updated Gantt Chart

 

6

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

In order for the Government to better assess the progress on this project, the Contractor shall submit quarterly updated Gantt charts.  The format shall be consistent with the initial submission contained in the Contractor’s technical proposal dated June 12, 2009, under [***].

 

6)             Risk Management Plans

 

Due to the Government’s need to periodically evaluate the risk evaluation and management strategy for this project, the Contractor shall provide updates to its risk management plan on a quarterly basis.  The plan contents should be consistent with the initial submission contained in the Contractor’s technical proposal dated June 12, 2009, under [***].

 

7

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

SECTION D—PACKAGING, MARKING AND SHIPPING

 

Report Deliverables

 

Unless otherwise specified by the Contracting Officer or the Contracting Officer’s representative, delivery of reports to be furnished to the Government under this contract (including invoices), shall be addressed as follows:

 

[***]

 

[***]

 

8

 

SECTION E—INSPECTION AND ACCEPTANCE

 

The Contracting Officer or a duly authorized representative will inspect and accept materials and services to be delivered under the contract.  Contractor inspector is hereby noted, as the Project Officer, and the place of inspection will be the contractor’s facilities.  In addition, the following clause is incorporated by reference:

 

FAR Clauses

 

FAR Clause No.52.246-9, INSPECTION OF RESEARCH AND DEVELOPMENT (SHORT FORM) (APR 1984)

 

9

 

SECTION F—DELIVERIES OR PERFORMANCE

 

F.1.   PERIOD OF PERFORMANCE

 

The period of performance of this contract is from the date of contract award to twelve (12) months after contract award.  Exercise of an option will extend the period of performance by an additional 12 months per contract option.

 

Delivery will be required F.O.B. Destination as set forth in FAR 52.247-35 F.O.B. DESTINATION WITHIN CONSIGNEE’S PREMISES (APR 1984).

 

F.2.   TECHNICAL REPORT REQUIREMENT

 

	
Item
    	
 
    	
Deliverable
    	
 
    	
Quantity
    	
 
    	
Due Date
    
	
1.
    	
 
    	
Technical Monthly Progress Report and Executive   Summary
    	
 
    	
1 Electronic Copy —
   Project Officer (PO)
   1 Electronic Copy — Contracting Officer (CO)
   1 Hard Copy - CO
    	
 
    	
30 days after contract award and by the 15th day of each month during the contract’s   period of performance. Not due when Final is due.
    
	
2.
    	
 
    	
Final Report
    	
 
    	
See above
    	
 
    	
Due on/before the completion date of the contract.
    
	
3.
    	
 
    	
Quarterly Gantt charts
    	
 
    	
See above
    	
 
    	
By the 15th day following the end of each quarterly   period.
    
	
4.
    	
 
    	
Quarterly Risk Management Plans
    	
 
    	
See above
    	
 
    	
By the 15th day following the end of each quarterly   period.
    

 

F.3.   CONTRACT DELIVERABLES

 

	
Item
    	
 
    	
Deliverable
    	
 
    	
Quantity
    	
 
    	
Due Date
    
	
1.
    	
 
    	
Updated Integrated Product Development Plan (IPDP)
    	
 
    	
1 Electronic Copy —
   Project Officer (PO)
   1 Electronic Copy —
   Contracting Officer (CO)
   1 Hard Copy - CO
    	
 
    	
14 days after contract award.
    
	
2.
    	
 
    	
FDA audit findings, including final reports, and   plans for addressing areas of conformance
    	
 
    	
1 Electronic Copy — P.O.
   1 Electronic Copy — C.O.
   1 Hard Copy - CO
    	
 
    	
Within 30 calendar days of an FDA audit of   contractor or subcontractor facilities.
    

 

F.4.   STOP WORK ORDER

 

The following clause is incorporated by reference:

 

FAR 52.242-15 STOP WORK ORDER (AUG 1989) with ALTERNATE I (APR 1984).

 

10

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

SECTION G—CONTRACT ADMINISTRATION DATA

 

G.1.       CONTRACTING OFFICER

 

1)             The Contracting Officer is the only individual who can legally commit the Government to the expenditure of public funds.  No person other than the Contracting Officer can make any changes to the terms, conditions, general provisions, or other stipulations of this contract.

 

2)             The Contracting Officer is the only person with the authority to act as agent of the government under this contract.  Only the Contracting Officer has authority to (1) direct or negotiate any changes in the statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimburse to the Contractor of any costs incurred during the performance of this contract; (5) otherwise change any terms and conditions of this contract.

 

3)             No information other than that which may be contained in an authorized modification to this contract, duly issued by the Contracting Officer, which may be received from any person employed by the US Government, other otherwise, shall be considered grounds for deviation from any stipulation of this contract.

 

G.1.       PROJECT OFFICER

 

The following Project Officers will represent the Government for the purpose of this contract:

 

[***], Project Officer

[***], Alternate Project Officer

 

Performance of the work hereunder shall be subject to the technical directions of the designated Project Officers for this contract.

 

As used herein, technical directions are directions to the Contractor, which fill in details, suggests possible lines of inquiry, or otherwise completes the general scope of work set forth herein.  These technical directions must be within the general scope of work, and may not alter the scope of work or cause changes of such a nature as to justify an adjustment in the stated contract price/cost, or any stated limitation thereof.  In the event that the Contractor feels that full implementation of any of these directions may exceed the scope of the contract, he or she shall notify the originator of the technical direction and the Contracting Officer in a letter separate of any required report(s) within two (2) weeks of the date of receipt of the technical direction and no action shall be taken pursuant to the direction.  If the Contractor fails to provide the required notification within the said two (2) week period that any technical direction exceeds the scope of the contract, then it shall be deemed for purposes of this contract that the technical direction was within the scope.  No technical direction, nor its fulfillment, shall alter or abrogate the rights and obligations fixed in this contract.

 

A Government Project Officer is not authorized to change any of the terms and conditions of this contract.  Changes shall be made only by the Contracting Officer by properly written modification(s) to the contract.  Any changes in Project Officer delegation will be made by the Contracting Officer in writing with a copy being furnished to the Contractor.

 

G.2.       KEY PERSONNEL

 

Pursuant to the Key Personnel clause incorporated in Section I of this contract, the following individual is considered to be essential to the work being performed hereunder:

 

[***], Principal Investigator

 

Prior to diverting any of the specific individuals to other programs, the Contractor shall notify the Contacting officer reasonably in advance and shall submit justification (including proposed substitutions) in sufficient detail to permit evaluation of the impact on the program.  No diversion shall be made by the contractor without the written consent of the Contracting Officer; provided that the Contracting Officer may ratify in writing such diversion and such ratification shall constitute the consent of the Contracting Officer.  The contract may be modified from time to time during the course of the contract to either add or delete personnel, as appropriate.

 

11

 

G.3.       INVOICE/FINANCING REQUEST AND CONTRACT FINANCIAL REPORTING

 

1)             The Contractor shall submit an original and one electronic copy of monthly contract invoices/financial reports to the address shown below:

 

DHHS/OS/ASPR/BARDA

 

Attn:  Contracting Officer

 

330 Independence Ave., S.W.

 

Room G640

 

Washington, D.C. 20201

 

2)             Contractor invoices/financial reports shall conform to the form, format, and content requirements of the instructions for Invoice/Financing requests and Contract Financial Reporting made a part of the contract in Section J.

 

3)             Monthly invoices must include the cumulative total expenses to date, adjusted (as applicable) to show any amounts suspended by the Government.

 

4)             The contractor agrees to immediately notify the Contracting Officer in writing if there is an anticipated overrun (any amount) or unexpended balance (greater than 10 percent) of the amount allotted to the contract, and the reasons for the variance.  Also refer to the requirements of the Limitation of Cost (FAR 52.232-20) clause in the contract.

 

5)             The date of receipt of a proper invoice/voucher by the Contracting Officer shall be used for the purpose of Prompt Payment Act time computations.

 

G.4.       REIMBURSEMENT OF COST (Apr 2000)

 

1)             The Government shall reimburse the Contractor the cost determined by the Contracting Officer to be allowable (hereinafter referred to as allowable cost) in accordance with the clause entitled Allowable Cost and Payment in Section I, Contract Clauses.  Examples of allowable costs include, but are not limited to, the following:

 

a)             All direct materials and supplies that are used in the performing of the work provided for under the contract, including those purchased for subcontracts and purchase orders.

 

b)             All direct labor, including supervisory, that is properly chargeable directly to the contract, plus fringe benefits.

 

c)              All other items of cost budgeted for and accepted in the negotiation of this basic contract or modifications thereto.

 

d)             Special expenditures which, upon request from the Contractor, the Contracting Officer approves as being an allowable cost under this contract, such as purchase or lease of office furniture or equipment, etc..

 

e)              All travel costs plus per diem or actual subsistence for personnel while in an actual travel status in direct performance of the work and services required under this contract.  These costs will be in accordance with the Contractor’s policy and subject to the following:

 

(i)                         Air travel shall be by the most direct route using “air coach” or “air tourist” (less than first class) unless it is clearly unreasonable or impractical (e.g., not available for reasons other than avoidable delay in making reservations, would require circuitous routing or entail additional expense offsetting the savings on fare, or would not make necessary connections).

 

(ii)                      Rail travel shall be by the most direct route, first class with lower berth or nearest equivalent.

 

(iii)                   Costs incurred for lodging, meals, and incidental expenses shall be considered reasonable and allowable to the extent that they do not exceed on a daily basis the per diem rates set forth in the Federal Travel Regulation (FTR).

 

12

 

(iv)                  Travel via privately owned automobile shall be reimbursed at not more than the current General Services Administration (GSA) FTR established mileage rate.

 

2)             Except as stated herein and under Section B, Paragraph B.3.  PROVISIONS APPLICABLE TO DIRECT COSTS, the Contractor shall not incur costs unless the prior written authorization of the Contracting Officer has been obtained.  When costs are incurred without such prior authorization, with the intent of claiming reimbursement as direct costs, it shall be at the contractor’s risk.

 

G. 5.    INDIRECT COST RATES

 

In accordance with Federal Acquisition Regulation (FAR) (48 CFR chapter 1) Clauses 52.216-7(d)(2), “Allowable Cost and Payment” incorporated by reference in this contract in Part II, Section I, the cognizant Contracting Officer representative responsible for negotiating provisional and/or final indirect cost rates is identified as follows:

 

Director, Division of Financial Advisory Services

Office of Acquisition Management and Policy

National Institutes of Health

6100 Building, Room 6B05

6100 Executive Boulevard, MSC 7540

Bethesda, MD 20892-7540

 

These rates are hereby incorporated without further action of the Contracting Officer.

 

G. 6.    POST AWARD EVALUATION OF PAST PERFORMANCE

 

Interim and final evaluations of contractor performance shall be conducted on this contract in accordance with FAR 42.15.  The final performance evaluation shall be completed at the time of completion of work.  Interim and final evaluations will be submitted to the Contractor as soon as practicable.  The Contractor will be permitted thirty days to review the document and to submit additional information or a rebutting statement.

 

G.7.       CONTRACT COMMUNICATIONS/CORRESPONDENCE (JULY 1999)

 

The Contractor shall identify all correspondence, reports, ad other data pertinent to this contract by imprinting the contract number from Page 1 of the contract.

 

G.8.       GOVERNMENT PROPERTY

 

1)             In addition to the requirements of the clause GOVERNMENT PROPERTY, incorporated in SECTION I of this contract, the Contractor shall comply with the provision of HHS Publication, “Contractor’s Guide for Control of Government Property,” which is incorporated into this contract by reference.  This document can be accessed at: httpa://www.knownet.hhs.gov/log/AgncyPolicy/HHSLogPolicy/contractorguide.htm.  Among other issues, this publication provides a summary of the Contractor’s responsibilities regarding purchasing authorization and inventory and reporting requirements under the contract.  A copy of this publication is available upon request o the Contacts Property Administrator.

 

2)             Notwithstanding the provisions outlined in the HHS Publication, “Contractor’s Guide for control of Government Property,” which is incorporated into this contract in paragraph a. above, the contractor shall use the form entitled “Report of Government Owned, contactor Held Property” for performing annual inventories required udder this contract.  This form is included as an attachment in SECTION J of the contract.

 

13

 

SECTION H—SPECIAL CONTRACT REQUIREMENTS

 

H. 1.    HUMAN SUBJECTS

 

Human Subjects: Research projects involving humans and/or human specimens can only be initiated with written approval by the BARDA Project Officer.

 

The Good Clinical Practice Regulations (GCP)(21 CFR Parts 50, 54, 56 312)(45 CFR Part 46)(ICH E6) as well as other applicable federal and state regulations will be standards that apply for use of human subject and/or human specimens in clinical studies.

 

If at any time during the life of the contract, the Contractor fails to comply with GCP as identified by regulations outline above , the Offeror shall have thirty (30) calendar days from the time such material failure is identified to cure such or initiate cure to the satisfaction of the USG Project Officer.  If the Offeror fails to take such an action or provide a remediation plan within the thirty (30) calendar day period, then the contract may be terminated.

 

Research involving human subjects shall not be conducted under this contract until the related protocol has been approved by DHHS and written notice of such approval has been provided by the Contracting Officer.  Additionally, prior to conducting the research, the Contractor must provide certification of Institutional Review Board (IRB) review and approval.

 

H. 2.    HUMAN MATERIALS

 

It is understood that the acquisition and supply of all human specimen material (including fetal material) used under this contract will be obtained by the Contractor in full compliance with applicable State and Local laws and the provisions of the Uniform Anatomical Gift Act in the United States and that no undue inducements, monetary or otherwise, will be offered to any person to influence their donation of human material.

 

H.3.       PROHIBITION ON THE USE OF APPROPRIATED FUNDS FOR LOBBYING ACTIVITIES AND HHSAR 352.270-10 ANTI-LOBBYING (Jan 2006)

 

The Contractor is hereby notified of the restrictions on the use of Department of Health and Human Service’s funding for lobbying of Federal, State and Local legislative bodies.

 

Section 1352 of Title 10, United Stated Code (Public Law 101-121, effective 12/23/89), among other things, prohibits a recipient (and their subcontractors) of a Federal contract, grant, loan, or cooperative agreement from using appropriated funds (other than profits from a federal contract) to pay any person for influencing or attempting to influence an officer or employee of any agency, a Member of Congress, an officer or employee of Congress, or an employee of a Member of Congress in connection with any of the following covered Federal actions; the awarding of any Federal contract; the making of any Federal grant; the making of any Federal loan; the entering into of any cooperative agreement; or the modification of any Federal contract, grant, loan, or cooperative agreement.  For additional information of prohibitions against lobbying activities, see FAR Subpart 3.8 and FAR Clause 52.203-12.

 

In addition, as set forth in HHSAR 352.270-10 “Anti-Lobbying” (January 2006), the current Department of Health and Human Services Appropriations Act provides that no part of any appropriation contained in this Act shall be used, other than for normal and recognized executive-legislative relationships, for publicity or propaganda purposes, for the preparation, distribution, or use of any kit, pamphlet, booklet, publication, radio, television, or video presentation designed to support, or defeat legislation pending before the Congress, or any State or Local legislature except in presentation to the Congress, or any State or Local legislative body itself.

 

The current Department of Health and Human Services Appropriations Act also provides that no part of any appropriation contained in this Act shall be used to pay the salary or expenses of any contract or grant recipient, or agent acting for such recipient, related to any activity designed to influence legislation or appropriations pending before the Congress, or any State or Local legislature.

 

(End of Clause)

 

14

 

H.4.       PRIVACY ACT APPLICABILITY (Apr 2000)

 

1)             Notification is hereby given that the Contractor and its employees are subject to criminal penalties for violation of the Privacy Act to the same extent as employees of the Government.  The Contractor shall assure that each of its employees knows the prescribed rules of conduct and that each is aware that he or she can be subjected to criminal penalty for violation of the Act.  A copy of 45 CFR Part 5b, Privacy Act Regulations, may be obtained at

 

http://www.gpoaccess.gov/cfr/index.html

 

2)             The Project Officer is hereby designated as the official who is responsible for monitoring contractor compliance with the Privacy Act.

 

3)             The Contractor shall follow the Privacy Act guidance as contained in the Privacy Act System of Records number 09-25- 0200.  This document may be obtained at the following link: http://oma.od.nih.gov/ms/privacy/pa-files/0200.htm

 

(End of Clause)

 

Note: Clinical trials cannot be initiated until the System Notice has been published and the Contracting Officer notifies the contractor.

 

H.5.       LABORATORY LICENSE REQUIREMENTS (May 1998)

 

The Contractor shall comply with all applicable requirements of Section 353 of the Public Health Service Act (Clinical Laboratory Improvement Act as amended).  This requirement shall also be included in any subcontract for services under the contract.

 

(End of Clause)

 

H.6.       DISSEMINATION OF INFORMATION (May 1998)

 

No information related to data obtained under this contract shall be released or publicized without the prior written consent of the Project Officer.

 

(End of Clause)

 

H.7.       IDENTIFICATION AND DISPOSITION OF DATA

 

The Contractor will be required to provide certain data generated under this contract to the Department of Health and Human Services (DHHS).  DHHS reserves the right to review any other data determined by DHHS to be relevant to this contract.  The contractor shall keep copies of all data required by the Food and Drug Administration (FDA) relevant to this contract for the time specified by the FDA.

 

H.8.       INFORMATION ON COMPLIANCE WITH ANIMAL CARE REQUIREMENTS

 

Registration with the U. S. Dept. of Agriculture (USDA) is required to use regulated species of animals for biomedical purposes.  USDA is responsible for the enforcement of the Animal Welfare Act (7 U.S.C. 2131 et. seq.), http://www.nal.usda.gov/awic/legislat/awa.htm.

 

The Public Health Service (PHS) Policy is administered by the Office of Laboratory Animal Welfare (OLAW) http://grants2.nih.gov/grants/olaw/olaw.htm.  An essential requirement of the PHS Policy http://grants2.nih.gov/grants/olaw/references/phspol.htm is that every institution using live vertebrate animals must obtain an approved assurance from OLAW before they can receive funding from any component of the U. S. Public Health Service.

 

15

 

The PHS Policy requires that Assured institutions base their programs of animal care and use on the Guide for the Care and Use of Laboratory Animals http://www.nap.edu/readingroom/books/labrats/ and that they comply with the regulations (9 CFR,

 

Subchapter A) http://www.nal.usda.gov/awic/legislat/usdaleg1.htm issued by the U.S. Department of Agriculture (USDA) under the Animal Welfare Act.  The Guide may differ from USDA regulations in some respects.  Compliance with the USDA regulations is an absolute requirement of this Policy.

 

The Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) http://www.aaalac.org is a professional organization that inspects and evaluates programs of animal care for institutions at their request.  Those that meet the high standards are given the Accredited status.  As of the 2002 revision of the PHS Policy, the only accrediting body recognized by PHS is the AAALAC.  While AAALAC Accreditation is not required to conduct biomedical research, it is highly desirable.  AAALAC uses the Guide as their primary evaluation tool.  They also use the Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching.  It is published by the Federated of Animal Science Societies http://www.fass.org.

 

H.9.                         REQUIREMENTS FOR ADEQUATE ASSURANCE OF PROTECTION OF VERTEBRATE ANIMAL SUBJECTS

 

The PHS Policy on Humane Care and Use of Laboratory Animals requires that applicant organizations proposing to use vertebrate animals file a written Animal Welfare Assurance with the Office for Laboratory Animal Welfare (OLAW), establishing appropriate policies and procedures to ensure the humane care and use of live vertebrate animals involved in research activities supported by the PHS. The PHS Policy stipulates that an applicant organization, whether domestic or foreign, bears responsibility for the humane care and use of animals in PHS-supported research activities.  Also, the PHS policy defines “animal” as “any live, vertebrate animal used, or intended for use, in research, research training, experimentation, biological testing or for related purposes.”  This Policy implements and supplements the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training, and requires that institutions use the Guide for the Care and Use of Laboratory Animals as a basis for developing and implementing an institutional animal care and use program.  This Policy does not affect applicable State or local laws or regulations that impose more stringent standards for the care and use of laboratory animals.  All institutions are required to comply, as applicable, with the Animal Welfare Act as amended (7 USC 2131 et. seq.) and other Federal statutes and regulations relating to animals.  These documents are available from the Office of Laboratory Animal Welfare, National Institutes of Health, Bethesda, MD 20892, (301) 496-7163.  See http://grants.nih.gov/grants/olaw/olaw.htm.

 

No PHS supported work for research involving vertebrate animals will be conducted by an organization, unless that organization is operating in accordance with an approved Animal Welfare Assurance and provides verification that the Institutional Animal Care and Use Committee (IACUC) has reviewed and approved the proposed activity in accordance with the PHS policy.  Applications may be referred by the PHS back to the institution for further review in the case of apparent or potential violations of the PHS Policy.  No award to an individual will be made unless that individual is affiliated with an assured organization that accepts responsibility for compliance with the PHS Policy.  Foreign applicant organizations applying for PHS awards for activities involving vertebrate animals are required to comply with PHS Policy or provide evidence that acceptable standards for the humane care and use of animals will be met.  Foreign applicant organizations are not required to submit IACUC approval, but should provide information that is satisfactory to the Government to provide assurances for the humane care of such animals.

 

H.10.                  APPROVAL OF REQUIRED ASSURANCE BY OLAW

 

Under governing regulations, federal funds which are administered by the Department of Health and Human Services, Office of Biomedical Advanced Research and Development Authority (BARDA) shall not be expended by the contractor for research involving live vertebrate animals, nor shall live vertebrate animals be involved in research activities by the contractor under this award unless a satisfactory assurance of compliance with 7 U.S.C. 2316 and 9 CFR Sections 2.25-2.28 is submitted within 30 days of the date of this award and approved by the Office of Laboratory Animal Welfare (OLAW).  Each performance site (if any) must also assure compliance with 7 U.S.C. 2316 and 9 CFR Sections 2.25-2.28 with the following restriction: Only activities which do not directly involve live vertebrate animals (i.e. are clearly severable and independent from those activities that do involve live vertebrate animals) may be conducted by the contractor or individual performance sites pending OLAW approval of their respective assurance of compliance with 7 U.S.C. 2316 and 9 CFR Sections 2.25-2.28.  Additional information regarding OLAW may be obtained via the Internet at http://grants2.nih.gov/grants/olaw/references/phspol.htm

 

16

 

H.11.                  PROHIBITION ON CONTRACTOR INVOLVEMENT WITH TERRORIST ACTIVITIES

 

The Contractor acknowledges that U.S. Executive Orders and Laws, including but not limited to Executive Order 13224 and Public Law 107-56, prohibit transactions with, and the provision of resources and support to, individuals and organizations associated with terrorism.  It is the legal responsibility of the contractor to ensure compliance with these Executive Orders and Laws.  This clause must be included in all subcontracts issued under this contract.

 

H.12.                  REGISTRATION WITH THE SELECT AGENT PROGRAM FOR WORK INVOLVING THE POSSESSION, USE, AND/OR TRANSFER OF SELECT BIOLOGICAL AGENTS OR TOXINS

 

Work involving select biological agents or toxins shall not be conducted under this contract until the contractor and any affected subcontractor(s) are granted a certificate of registration or are authorized to work with the applicable select agents.

 

For prime or subcontract awards to domestic institutions who possess, use, and/or transfer Select Agents under this contract, the institution must complete registration with the Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (DHHS) or the Animal and Plant Health Inspection Services (APHIS), U.S. Department of Agriculture (USDA), as applicable, before performing work involving Select Agents, in accordance with 42 CFR 73.  No Government funds can be used for work involving Select Agents, as defined in 42 CFR 73, if the final registration certificate is denied.

 

For prime or subcontract awards to foreign institutions who possess, use, and/or transfer Select Agents under this contract, the institution must provide information satisfactory to the Government that a process equivalent to that described in 42 CFR 73 (http://www.cdc.gov/od/sap/docs/42cfr73.pdf ) for U.S. institutions is in place and will be administered on behalf of all Select Agent work sponsored by these funds before using these funds for any work directly involving the Select Agents.  The contractor must provide information addressing the following key elements appropriate for the foreign institution: safety, security, training, procedures for ensuring that only approved/appropriate individuals have access to the Select Agents, and any applicable laws, regulations and policies equivalent to 42 CFR 73.  The Government will assess the policies and procedures for comparability to the U.S. requirements described in 42 CFR Part 73.  When requested by the contracting officer, the contractor shall provide key information delineating any laws, regulations, policies, and procedures applicable to the foreign institution for the safe and secure possession, use, and transfer of Select Agents.  This includes summaries of safety, security, and training plans, and applicable laws, regulations, and policies.  For the purpose of security risk assessments, the contractor must provide the names of all individuals at the foreign institution who will have access to the Select Agents and procedures for ensuring that only approved and appropriate individuals have access to Select Agents under the contract.

 

Listings of HHS select agents and toxins, biologic agents and toxins, and overlap agents or toxins as well as information about the registration process, can be obtained on the Select Agent Program Web site at http://www.cdc.gov/od/sap/.

 

H.13.                  OPTION PROVISION

 

Unless the Government exercises its option pursuant to the Option Clause set forth in Section I, Paragraph I.2., the contract will consist only of CLIN 0001 of the Statement of Work as defined in Sections C and F of the contract.  Pursuant to clause 52.217-7 set forth in Section I of this contract, under I.3., the Government may, by unilateral contract modification, require the Contractor to perform any of the additional CLIN’s listed in Section B, Paragraph B.2., and as also defined in Sections C and F of this contract.  If the Government exercises an option, notice must be given at least 60 days prior to the expiration date of this contract.  The amount of the contract will then be increased as set forth in Section B, Paragraph B.2., and the contract’s period of performance will be extended by one year for each option.

 

H. 14. EPA ENERGY STAR REQUIREMENTS

 

In compliance with Executive Order 12845 (requiring Agencies to purchase energy efficient computer equipment) all microcomputers, including personal computers, monitors, and printers that are purchased using Government funds in performance of a contract shall be equipped with or meet the energy efficient low-power standby feature as defined by the EPA Energy Star program unless the equipment always meets EPA Energy Star efficiency levels.  The microcomputer, as configured with all components, must be Energy Star compliant.

 

This low-power feature must already be activated when the computer equipment is delivered to the agency and be of equivalent functionality of similar power managed models.  If the equipment will be used on a local area network, the vendor must provide

 

17

 

equipment that is fully compatible with the network environment.  In addition, the equipment will run commercial off-the-shelf software both before and after recovery from its energy conservation mode.

 

H. 15. ACKNOWLEDGMENT OF FEDERAL FUNDING

 

A.            Section 507 of P.L. 104-208 mandates that contractors funded with Federal dollars, in whole or in part, acknowledge Federal funding when issuing statements, press releases, requests for proposals, bid solicitations and other documents.  Contractors are required to state (1) the percentage and dollar amounts of the total program or project costs financed with Federal money, and (2) the percentage and dollar amount of the total costs financed by nongovernmental sources.

 

This requirement is in addition to the continuing requirement to provide an acknowledgment of support and disclaimer on any publication reporting the results of a contract funded activity.

 

B.            Publication and Publicity

 

Publications: Any manuscript or scientific meeting abstract containing data generated under this contract must be submitted for BARDA Project Officer review no less than thirty (30) calendar days for manuscripts and fifteen (15) calendar days for abstracts before submission for public presentation or publication.  Contract support shall be acknowledged in all such publications.  A “publication” is defined as an issue of printed material offered for distribution or any communication or oral presentation of information.

 

The Contractor shall acknowledge the support of the Department of Health and Human Service, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, whenever publicizing the work under this contract in any media by including an acknowledgment substantially as follows:

 

“This project has been funded in whole or in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201000011C.”

 

C.            Press Releases

 

(a)         Pursuant to Section 508 of Public Law 105-78, the contractor shall clearly state, when issuing statements, press releases, requests for proposals, bid solicitations and other documents describing projects or programs funded in whole or in part with Federal money that: (1) the percentage of the total costs of the program or project which will be financed with Federal money; (2) the dollar amount of Federal funds for the project or program; and (3) the percentage and dollar amount of the total costs of the project or program that will be financed by nongovernmental sources.

 

(b)         The Contractor agrees to accurately and factually represent the work conducted under this contract in all press releases.  Misrepresenting contract results or releasing information that is injurious to the integrity of BARDA may be construed as improper conduct.  Press releases shall be considered to include the public release of information to any medium, excluding peer-reviewed scientific publications.  The contractor shall ensure that the Project Officer has received an advance copy of any press release related to this contract not less than four (4) working days prior to the issuance of the press release.

 

H. 16.               REPORTING MATTERS INVOLVING FRAUD, WASTE AND ABUSE

 

Anyone who becomes aware of the existence or apparent existence of fraud, waste and abuse in DHHS funded programs is encouraged to report such matters to the HHS Inspector General’s Office in writing or on the Inspector General’s Hotline.  The toll-free number is 1-800-HHS-TIPS (1-800-447-8477).  All telephone calls will be handled confidentially.  The e-mail address is Htips@os.dhhs.gov.

 

Office of Inspector General

Department of Health and Human Services

TIPS HOTLINE

P.O. Box 23489

Washington, DC 20026

 

18

 

H. 17.               MANUFACTURING STANDARDS

 

The Good Manufacturing Practice Regulations (GMP)(21 CFR Parts 210-211) and regulations pertaining to biological products (21 CFR Part 600) and regulations pertaining to diagnostic products (21 CFR Part 860) will be the standard to be applied for manufacturing, processing, packaging, storage and delivery of this product.

 

If at any time during the life of the contract, the Contractor fails to comply with GMP in the manufacturing, processing, packaging, storage, stability and other testing of the manufactured drug substance or product and delivery of this product and such failure results in a material adverse effect on the safety, purity or potency of the product (a material failure) as identified by the FDA, the Contractor shall have thirty (30) calendar days from the time such material failure is identified to cure such material failure.  If, within the thirty (30) calendar day period, the Contractor fails to take such an action to the satisfaction of the USG Project Officer, or fails to provide a remediation plan that is acceptable to the Project Officer, then the contract may be terminated.

 

H.18.                  EXPORT CONTROL NOTIFICATION

 

Offerors are responsible for ensuring compliance with all export control laws and regulations that maybe applicable to the export of and foreign access to their proposed technologies.  Offerors may consult with the Department of State with any questions regarding the International Traffic in Arms Regulation (ITAR) (22 CRF Parts 120-130) and /or the Department of Commerce regarding the Export Administration Regulations (15 CRF Parts 730-774).

 

19

 

PART II — CONTRACT CLAUSES

 

SECTION I - CONTRACT CLAUSES

 

I.1.      FAR 52.252-2, CLAUSES INCORPORATED BY REFERENCE (FEBRUARY 1998)

 

This contract incorporates the following clauses by reference, with the same force and effect as if they were given in full text.  Upon request, the Contracting Officer will make their full text available.  Also, the full text of a clause may be accessed electronically at these addresses: http://www.arnet.gov

 

A.      General Clauses for Cost-Reimbursement Research and Development General Clauses

 

(1)         FEDERAL ACQUISITION REGULATION (FAR) (48 CFR CHAPTER 1) CLAUSES:

 

	
FAR
   CLAUSE NO.
    	
 
    	
DATE
    	
 
    	
TITLE
    
	
52.202-1
    	
 
    	
Jul 2004
    	
 
    	
Definitions
    
	
52.203-3
    	
 
    	
Apr 1984
    	
 
    	
Gratuities (Over $100,000)
    
	
52.203-5
    	
 
    	
Apr 1984
    	
 
    	
Covenant Against Contingent Fees (Over $100,000)
    
	
52.203-6
    	
 
    	
Sep 2006
    	
 
    	
Restrictions on Subcontractor Sales to the   Government (Over $100,000)
    
	
52.203-7
    	
 
    	
Jul 1995
    	
 
    	
Anti-Kickback Procedures (Over $100,000)
    
	
52.203-8
    	
 
    	
Jan 1997
    	
 
    	
Cancellation, Rescission, and Recovery of Funds for   Illegal or Improper Activity (Over $100,000)
    
	
52.203-10
    	
 
    	
Jan 1997
    	
 
    	
Price or Fee Adjustment for Illegal or Improper   Activity (Over $100,000)
    
	
52.203-12
    	
 
    	
Sep 2007
    	
 
    	
Limitation on Payments to Influence Certain Federal   Transactions (Over $100,000)
    
	
52.203-13
    	
 
    	
Dec 2008
    	
 
    	
Contractor Code of Business Ethics and Conduct (over   $5,000,000)
    
	
52.203-14
    	
 
    	
Dec 2007
    	
 
    	
Display of Hotline Poster
    
	
52.204-4
    	
 
    	
Aug 2000
    	
 
    	
Printed or Copied Double-Sided on Recycled Paper   (Over $100,000)
    
	
52.204-7
    	
 
    	
Apr 2008
    	
 
    	
Central Contractor Registration
    
	
52.209-6
    	
 
    	
Sep 2006
    	
 
    	
Protecting the Government’s Interests When   Subcontracting With Contractors Debarred, Suspended, or Proposed for   Debarment (Over $25,000)
    
	
52.215-2
    	
 
    	
Mar 2009
    	
 
    	
Audit and Records - Negotiation (Over $100,000)
    
	
52.215-8
    	
 
    	
Oct 1997
    	
 
    	
Order of Precedence - Uniform Contract Format
    
	
52.215-10
    	
 
    	
Oct 1997
    	
 
    	
Price Reduction for Defective Cost or Pricing Data
    
	
52.215-12
    	
 
    	
Oct 1997
    	
 
    	
Subcontractor Cost or Pricing Data (Over $500,000)
    
	
52.215-14
    	
 
    	
Oct 1997
    	
 
    	
Integrity of Unit Prices (Over $100,000)
    
	
52.215-15
    	
 
    	
Oct 2004
    	
 
    	
Pension Adjustments and Asset Reversions
    
	
52.215-17
    	
 
    	
Oct 1997
    	
 
    	
Waiver of Facilities Capital Cost of Money
    
	
52.215-18
    	
 
    	
Jul 2005
    	
 
    	
Reversion or Adjustment of Plans for Post-Retirement   Benefits (PRB) other than Pensions
    

 

20

 

	
52.215-19
    	
 
    	
Oct 1997
    	
 
    	
Notification of Ownership Changes
    
	
52.215-21
    	
 
    	
Oct 1997
    	
 
    	
Requirements for Cost or Pricing Data or Information   Other Than Cost or Pricing Data — Modifications
    
	
52.216-7
    	
 
    	
Dec 2002
    	
 
    	
Allowable Cost and Payment (Note: the following   language is included in this clause — “(3) The designated payment office   will make interim payments for contract financing on the 30th day   after the designated billing office receives a proper payment request...”
    
	
52.216-8
    	
 
    	
Mar 1997
    	
 
    	
Fixed Fee
    
	
52.217-7
    	
 
    	
March 1989
    	
 
    	
Option for Increased Quantity - Separately Priced   Line Item (Note: the following language is included in this clause — “....The   Contracting Officer may exercise the option by written notice to the Contractor   within 60 days prior to the expiration of this contract ....”)
    
	
52.219-8
    	
 
    	
May 2004
    	
 
    	
Utilization of Small Business Concerns (Over   $100,000)
    
	
52.219-9
    	
 
    	
Apr 2008
    	
 
    	
Small Business Subcontracting Plan (Over $500,000)
    
	
52.219-16
    	
 
    	
Jan 1999
    	
 
    	
Liquidated Damages - Subcontracting Plan (Over   $500,000)
    
	
52.222-2
    	
 
    	
Jul 1990
    	
 
    	
Payment for Overtime Premium (Over $100,000) (Note:   The dollar amount in paragraph (a) of this clause is $0 unless otherwise   specified in the contract.)
    
	
52.222-19
    	
 
    	
Aug 2009
    	
 
    	
Child Labor — Cooperation with Authorities and   Remedies
    
	
52.222-3
    	
 
    	
Jun 2003
    	
 
    	
Convict Labor
    
	
52.222-21
    	
 
    	
Feb 1999
    	
 
    	
Prohibition of Segregated Facilities
    
	
52.222-26
    	
 
    	
Mar 2007
    	
 
    	
Equal Opportunity
    
	
52.222-35
    	
 
    	
Sep 2006
    	
 
    	
Equal Opportunity for Special Disabled Veterans,   Veterans of the Vietnam Era, and Other Eligible Veterans
    
	
52.222-36
    	
 
    	
Jun 1998
    	
 
    	
Affirmative Action for Workers with Disabilities
    
	
52.222-37
    	
 
    	
Sep 2006
    	
 
    	
Employment Reports on Special Disabled Veterans,   Veterans of the Vietnam Era, and Other Eligible Veterans
    
	
52.222-39
    	
 
    	
Dec 2004
    	
 
    	
Notification of Employee Rights Concerning Payment   of Union Dues or Fees
    
	
52.222-50
    	
 
    	
Feb 2009
    	
 
    	
Combating Trafficking in Persons
    
	
52.222-54
    	
 
    	
Jan 2009
    	
 
    	
Employment Eligibility Verification
    
	
52.223-6
    	
 
    	
May 2001
    	
 
    	
Drug-Free Workplace
    
	
52.223-14
    	
 
    	
Aug 2003
    	
 
    	
Toxic Chemical Release Reporting (Over $100,000)
    
	
52.224-1
    	
 
    	
April 1984
    	
 
    	
Privacy Act Notification
    
	
52.224-2
    	
 
    	
April 1984
    	
 
    	
Privacy Act
    
	
52.225-1
    	
 
    	
Feb 2009
    	
 
    	
Buy American Act - Supplies
    
	
52.225-13
    	
 
    	
Jun 2008
    	
 
    	
Restrictions on Certain Foreign Purchases
    
	
52.227-1
    	
 
    	
Dec 2007
    	
 
    	
Authorization and Consent, Alternate I (Apr 1984)
    

 

21

 

	
52.227-2
    	
 
    	
Dec 2007
    	
 
    	
Notice and Assistance Regarding Patent and Copyright   Infringement (Over $100,000)
    
	
52.227-11
    	
 
    	
Dec 2007
    	
 
    	
Patent Rights - Retention by the Contractor (Short   Form) (Note: In accordance with FAR 27.303(a)(2), paragraph (f) is   modified to include the requirements in FAR 27.303(a)(2)(i) through   (iv). The frequency of reporting in (i) is annual.
    
	
52.227-14
    	
 
    	
Dec 2007
    	
 
    	
Rights in Data — General
    
	
52.229-8
    	
 
    	
March 1990
    	
 
    	
Foreign Cost-Reimbursement Contracts
    
	
52.230-4
    	
 
    	
Oct 2008
    	
 
    	
Disclosure and Consistency of Cost Accounting   Practices for Contracts Awarded to Foreign Concerns
    
	
52.232-9
    	
 
    	
Apr 1984
    	
 
    	
Limitation on Withholding of Payments
    
	
52.232-17
    	
 
    	
Oct 2008
    	
 
    	
Interest (Over $100,000)
    
	
52.232-20
    	
 
    	
Apr 1984
    	
 
    	
Limitation of Cost
    
	
52.232-23
    	
 
    	
Jan 1986
    	
 
    	
Assignment of Claims
    
	
52.232-25
    	
 
    	
Oct 2008
    	
 
    	
Prompt Payment, Alternate I (Feb 2002)
    
	
52.232-33
    	
 
    	
Oct 2003
    	
 
    	
Payment by Electronic Funds Transfer—Central   Contractor Registration
    
	
52.233-1
    	
 
    	
Jul 2002
    	
 
    	
Disputes
    
	
52.233-3
    	
 
    	
Aug 1996
    	
 
    	
Protest After Award, Alternate I (Jun 1985)
    
	
52.233-4
    	
 
    	
Oct 2004
    	
 
    	
Applicable Law for Breach of Contract Claim
    
	
52.242-1
    	
 
    	
Apr 1984
    	
 
    	
Notice of Intent to Disallow Costs
    
	
52.242-3
    	
 
    	
May 2001
    	
 
    	
Penalties for Unallowable Costs (Over $500,000)
    
	
52.242-4
    	
 
    	
Jan 1997
    	
 
    	
Certification of Final Indirect Costs
    
	
52.242-13
    	
 
    	
Jul 1995
    	
 
    	
Bankruptcy (Over $100,000)
    
	
52.243-2
    	
 
    	
Aug 1987
    	
 
    	
Changes - Cost Reimbursement, Alternate V (Apr 1984)
    
	
52.244-2
    	
 
    	
Jun 2007
    	
 
    	
Subcontracts, Alternate II (Aug 1998) *If written   consent to subcontract is required, the identified subcontracts are listed in   Section B, Paragraph B.4., Advance Understandings.
    
	
52.244-5
    	
 
    	
Dec 1996
    	
 
    	
Competition in Subcontracting (Over $100,000)
    
	
52.244-6
    	
 
    	
Feb 2009
    	
 
    	
Subcontracts for Commercial Items
    
	
52.245-1
    	
 
    	
June 2007
    	
 
    	
Government Property
    
	
52.245-9
    	
 
    	
Jun 2007
    	
 
    	
Use and Charges
    
	
52.246-23
    	
 
    	
Feb 1997
    	
 
    	
Limitation of Liability (Over $100,000)
    
	
52.249-6
    	
 
    	
May 2004
    	
 
    	
Termination (Cost-Reimbursement)
    
	
52.253-1
    	
 
    	
Jan 1991
    	
 
    	
Computer Generated Forms
    

 

22

 

(2)         DEPARTMENT OF HEALTH AND HUMAN SERVICES ACQUISITION REGULATION (HHSAR) (48 CFR CHAPTER 3) CLAUSES:

 

	
HHSAR
   CLAUSE NO.
    	
 
    	
DATE
    	
 
    	
TITLE
    
	
352.202-1
    	
 
    	
Jan 2006
    	
 
    	
Definitions - with Alternate paragraph (h) (Jan   2001)
    
	
352.216-72
    	
 
    	
Jan 2006
    	
 
    	
Additional Cost Principles
    
	
352.223-70
    	
 
    	
Jan 2006
    	
 
    	
Safety and Health
    
	
352.224-70
    	
 
    	
Jan 2006
    	
 
    	
Confidentiality of Information (Note: The following   information is covered by this clause- Data obtained from human subjects)
    
	
352.228-7
    	
 
    	
Dec 1991
    	
 
    	
Insurance - Liability to Third Persons
    
	
352.232-9
    	
 
    	
Jan 2006
    	
 
    	
Withholding of Contract Payments
    
	
352.233-70
    	
 
    	
Jan 2006
    	
 
    	
Litigation and Claims
    
	
352.242-71
    	
 
    	
Apr 1984
    	
 
    	
Final Decisions on Audit Findings
    
	
352.249-14
    	
 
    	
Jan 2006
    	
 
    	
Excusable Delays
    
	
352.270-5
    	
 
    	
Jan 2006
    	
 
    	
Key Personnel
    
	
352.270-6
    	
 
    	
Jan 2006
    	
 
    	
Publications and Publicity
    
	
352.270-7
    	
 
    	
Jan 2006
    	
 
    	
Paperwork Reduction Act
    
	
352.270-9
    	
 
    	
Jan 2006
    	
 
    	
Care of Live Vertebrate Animals
    
	
352.270-10
    	
 
    	
Jan 2006
    	
 
    	
Anti-Lobbying
    
	
352.333-7001
    	
 
    	
Undated
    	
 
    	
Choice of Law (Overseas)
    

 

[End of GENERAL CLAUSES FOR A COST-REIMBURSEMENT RESEARCH AND DEVELOPMENT CONTRACT].

 

23

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACHMENTS

 

SECTION J - LIST OF ATTACHMENTS

 

1)             Work Statement, [***]

 

2)             Invoice/Financing Request and Contract Financial Reporting Instructions for Cost-Reimbursement Contracts, 6 pages

 

24

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

PART IV — REPRESENTATIONS AND INSTRUCTIONS

 

SECTION K - REPRESENTATIONS, CERTIFICATIONS AND OTHER STATEMENTS OF OFFERORS

 

The following documents are incorporated by reference in this contract:

 

1)             Annual Representations and Certifications completed at the Online Representations Applications (ORCA) website.

 

2)             [***]

 

3)             Human Subjects Assurance Identification Number FW A00004396.

 

4)             Animal Welfare Assurance Number A-5554-01.

 

END OF THE SCEHDULE

 

(CONTRACT)

 

25

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

NO. 11. THIS   ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS  The above numbered solicitation is amended   as set forth in Item 14. The hour and date specified for receipt of   Offers  is extended,  is not extended. Offers must acknowledge   receipt of this amendment prior to the hour and date specified in the   solicitation or as amended, by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of   this amendment, you desire to change an offer already submitted, such change   may be made by telegram or letter, provided each telegram or letter makes   reference to the solicitation and this amendment, and is received prior to   the opening hour and date specified. 12. ACCOUNTING AND APPROPRIATION DATA   (If required) APPROPRIATION: 75-1011-0140; CAN: 1990087; OBJECT CLASS: 25329;   ; AMOUNT: $[***] 13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS,   IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14. ORDER NO. IN ITEM   10A. E. IMPORTANT: Contractor [ ] is not, [X] is required to sign this   document and return 2 copies to the issuing office. 14. DESCRIPTION OF   AMENDMENT/MODIFICATION (Organized by UCF section headings, including   solicitation/contract subject matter where feasible) PURPOSES: (1) To modify   the dollar amounts for Options #1and #2; (2) to exercise Option #1 based upon   the revised dollar amount; (3) to move several milestones in the Statement of   Work to different project years; and (4) to add indirect rates that apply   specifically to this contract. No other terms or conditions are changed by   this modification Funds Obligated: Total Base Contract Dollar Amount:   Contract Expiration Date: $[***] $[***] (changed) November 15, 2011(changed)   Except as provided herein, all terms and conditions of the document   referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in   full force and effect. (Signature of Contracting Officer) NSN   7540-01-152-8070 OMB No. 0990–0115 STANDARD FORM 30 (REV. 10-83) FAR (48 CFR)   53.243 123269097 v2 15A. NAME AND TITLE OF SIGNER (Type or print) [***] [***]   16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print) [***], Contracting   Officer 15B. CONTRACTOR/OFFEROR /s/ [***] (Signature of person authorized to   sign) 15C. DATE SIGNED 17/9/10 16B. UNITED STATES OF AMERICA BY /s/ [***]   16C. DATE SIGNED September 23, 2010 () A.THIS CHANGE ORDER IS ISSUED PURSUANT   TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE   CONTRACT B.THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE   ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date,   etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).  C.THIS SUPPLEMENTAL AGREEMENT IS ENTERED   INTO PURSUANT TO AUTHORITY OF: FAR 1.602-1 and mutual agreement of the   parties D.OTHER (Specify type of modification and authority) AMENDMENT OF   SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE PAGE OF PAGES 1 3   2. AMENDMENT/MODIFICATION NO 1 3. EFFECTIVE DATE See Block 16C 4.   REQUISITION/PURC N/A 5. PROJECT NO. (If applicable) N/A 6. ISSUED BYCODE 7.   ADMINISTERED BY (If other than Item 6)CODE HHS/OS/ASPR/AMCG 330 Independence   Avenue, SW Room G640 Washington, DC 20201 8. NAME AND ADDRESS OF CONTRACTOR   (No., street, county, State and ZIP Code) Bavarian Nordic A/S Hejreskovvej   10A 3490 Kvistgård Denmark (X) 9A. AMENDMENT OF SOLICITATION NO. 9B. DATED   (SEE ITEM 11) x 10A. MODIFICATION OF CONTRACT/ORDER HHSO100201000011C 10B.   DATED (SEE ITEM 13) November 16, 2009 CODE FACILITY CODE 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
SPECIAL   PROVISIONS
    	
Contract   No: HHSO100201000011C
   Modification No: 1
    	
 
    

 

The basic contract award is hereby modified as follows:

 

1.                          Contract Option #1 is hereby exercised, but at a reduced amount.  The revised Option #1 amount is shown below.  This information replaces CLIN 0002, which is set forth under Section B.  Supplies or Services and Prices/Costs, A. CONTRACT LINE ITEM NUMBER (CLIN’S), 2. Contract Options.

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0002
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
													

 

2.                          The dollar of Option #2 is increased to offset the reduction to Option #1. The revised Option #2 amount is shown below. This information replaces CLIN 0003, which is set forth under Section B. Supplies or Services and Prices/Costs, A. CONTRACT LINE ITEM NUMBER (CLIN’S), 2. Contract Options.

 

	
0003
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    

 

3.                          Under Section C, Description/Specifications, C.1. STATEMENT OF WORK is revised to move several milestones to different project years.  Specifically the following Base Contract milestones are moved:  [***]

 

4.                          The contract’s expiration date is extended by twelve months due to the exercise of Option #1, as set forth in Section F. Deliveries or Performance, under F.1. Period of Performance.  The revised expiration date is November 15, 2011.

 

5.                          [***]

 

(a) [***]:

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Director, Division of Financial Advisory Services
 Office of Acquisition Management and Policy
 National Institutes of Health
 6100 Building, Room 6B05
 6100 Executive Boulevard, MSC 7540
 Bethesda, MD 20892-7540

 

(b)         [***]:

 

[***]
 [***]

 

All other terms and conditions of the contract are unchanged and remain in full force and effect.

 

3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A NO. 11.   THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS The above numbered   solicitation is amended as set forth in Item 14. The hour and date specified   for receipt of Offers is extended, is not extended. Offers must acknowledge   receipt of this amendment prior to the hour and date specified in the   solicitation or as amended, by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of   this amendment, you desire to change an offer already submitted, such change   may be made by telegram or letter, provided each telegram or letter makes   reference to the solicitation and this amendment, and is received prior to   the opening hour and date specified. 12. ACCOUNTING AND APPROPRIATION DATA   (if required) N/A 13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF   CONTRACTS/ORDERS, IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.   CONTRACT ORDER NO. IN ITEM 10A. office, appropriation date, etc.) SET FORTH   IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b). E. IMPORTANT:   Contractor [X] is not, [ ] is required to sign this document and return   copies to the issuing office. 14. DESCRIPTION OF AMENDMENT/MODIFICATION   (Organized by UCF section headings, including solicitation/contract subject   matter where feasible) PURPOSE: This modification revises the accounting data   that was listed in Modification #1 under Block #12 to read as follows:   Appropriation – 7509/100140 Appropriation – 7510/110140 CAN - 1990987 Amount   - $[***] CAN - 1990987 Amount - $[***] All other terms and conditions of the   contract are unchanged and remain in full force and effect. Except as   provided herein, all terms and conditions of the document referenced in Item   9A or 10A, as heretofore changed, remains unchanged and in full force and   effect. NSN 7540-01-152-8070 OMB No. 0990–0115 STANDARD FORM 30 (REV. 10-83)   FAR (48 CFR) 53.243 123269097 v2 15A. NAME AND TITLE OF SIGNER (Type or   print) 16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print) [***],   Contracting Officer 15B. CONTRACTOR/OFFEROR (Signature of person authorized   to sign) 15C. DATE SIGNED 16B. UNITED STATES OF AMERICA BY /s/ [***]   (Signature of Contracting Officer) 16C. DATE SIGNED 9/30/2010 () A.THIS   CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH   IN ITEM 14 ARE MADE IN THE B.THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO   REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying C.THIS   SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF: D.OTHER   (Specify type of modification and authority) AMENDMENT OF   SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE PAGE OF PAGES 1 1   2. AMENDMENT/MODIFICATION NO 002 3. EFFECTIVE DATE See Block 16C. 4.   REQUISITION/PURC N/A 5. PROJECT NO. (If applicable) 6. ISSUED BYCODE 7.   ADMINISTERED BY (If other than Item 6)CODE HHS/OS/ASPR/AMCG 330 Independence   Avenue, SW Room G640 Washington, DC 20201 8. NAME AND ADDRESS OF CONTRACTOR   (No., street, county, State and ZIP Code) Bavarian Nordic A/S Hejreskovvej   10A 3490 Kvistgård Denmark (x) 9A. AMENDMENT OF SOLICITATION NO. 9B. DATED   (SEE ITEM 11) x 10A. MODIFICATION OF CONTRACT/ORDER HHSO100201000011C 10B.   DATED (SEE ITEM 13) November 16, 2009 CODE FACILITY CODE 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A NO. 11.   THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS ~ The above numbered   solicitation is amended as set forth in Item 14. The hour and date specified   for receipt of Offers ~ is extended, ~is not extended. Offers must   acknowledge receipt of this amendment prior to the hour and date specified in   the solicitation or as amended, by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of   this amendment, you desire to change an offer already submitted, such change   may be made by telegram or letter, provided each telegram or letter makes   reference to the solicitation and this amendment, and is received prior to   the opening hour and date specified. 12. ACCOUNTING AND APPROPRIATION DATA   (if required) N/A 13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF   CONTRACTS/ORDERS, IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.   FAR 1.602-1 and mutual agreement of the parties E. IMPORTANT: Contractor [ ]   is not, [X] is required to sign this document and return 2 copies to the   issuing office. 14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF   section headings, including solicitation/contract subject matter where   feasible.) PURPOSES: [***] No other terms or conditions are changed by this   modification. See continuation sheet. Funds Obligated: $0 Total Base Contract   Dollar Amount: $[***] Contract Expiration Date: November 15, 2011 (unchanged)   Except as provided herein, all terms and conditions of the document   referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in   full force and effect. NSN 7540-01-152-8070 OMB No. 0990–0115 STANDARD FORM   30 (REV. 10-83)FAR (48 CFR) 53.243 123269097 v2 15A. NAME AND TITLE OF SIGNER   (Type or print) [***], EVP 16A. NAME AND TITLE OF CONTRACTING OFFICER (Type   or print) [***], Contracting Officer 15B. CONTRACTOR/OFFEROR /s/ [***]   (Signature of person authorized to sign) 15C. DATE SIGNED 8 April 2011 16B.   UNITED STATES OF AMERICA BY/s/ [***] (Signature of Contracting Officer) 16C.   DATE SIGNED April 8, 2011 (Y) A.THIS CHANGE ORDER IS ISSUED PURSUANT TO:   (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT   ORDER NO. IN ITEM 10A. B.THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO   REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office,   appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF   FAR 43.103(b). Y C.THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO   AUTHORITY OF: D.OTHER (Specify type of modification and authority) AMENDMENT   OF SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE PAGE OF PAGES 1   5 2. AMENDMENT/MODIFICATION NO 3 3. EFFECTIVE DATE See Block 16C 4. REQUISITION/PURC   N/A 5. PROJECT NO. (If applicable) 6. ISSUED BYCODE 7. ADMINISTERED BY (If   other than Item 6)CODE HHS/ASPR/AMCG 330 Independence Avenue, SW Room G640   Washington, DC 20201 8. NAME AND ADDRESS OF CONTRACTOR (No., street, county,   State and ZIP Code) Bavarian Nordic A/S Hejreskovvej 10A 3490 Kvistgård   Denmark (x) 9A. AMENDMENT OF SOLICITATION NO. 9B. DATED (SEE ITEM 11) x 10A.   MODIFICATION OF CONTRACT/ORDER HHSO100201000011C 10B. DATED (SEE ITEM 13)   November 16, 2009 CODE: FACILITY CODE: 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Continuation   Sheet
    	
Contract   No: HHSO100201000011C
   Modification No: 3
    	
 
    

 

Modification No. 003 (the “Mod 3”) to Contract No. HHS0100201000011C, as amended to the date of Mod 3, (the “Existing Contract”) entered into and made effective as of the date imprinted in Block 16C of the Standard Form 30, is by and between the United States of America—which is represented by the Department of Health and Human Services, Biomedical Advanced Research and Development Authority—and Bavarian Nordic (“BN”), a company registered in Denmark, with a principal place of business located at Hejreskovvej 10 A, 3490, Kvistgard, Denmark, (USG and BN each being referred to as a “Party” and collectively as the “Parties”) who jointly agree to be bound by the terms and conditions hereof,

 

The basic contract award is revised as follows:

 

1.                            As a result of revisions to the Statement of Work, the dollar amounts for optional CLIN’s 0003, 0004, 0005, and 0006 are modified.  Section B. Supplies or Services and Prices/Costs, A. CONTRACT LINE ITEM NUMBER (CLIN’S), 2. Contract Options are therefore modified as shown below:

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL EST.
   CPFF
    	
 
    
	
0003
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0004
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0005
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0006
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    

 

All funding above the funds previously awarded are at a fee of [***]%.

 

2.                            Section B.4 Advanced Understandings, are revised as shown below:

 

3)  [***]

[***]

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

[***]

 

[***]

 

[***]

 

4)  Protocols

 

The Contractor shall distribute draft study plans and protocols for USG review prior to the conduct of a Study Design Review Meeting between the USG and the contractor as part of the pre­approval process as described in paragraph B.3.

 

5)  Access to Documentation and Interaction with Regulatory Agencies

 

The contractor shall provide the USG with a non-redacted copy of any FDA Form-482, Form FDA-483, and Establishment Inspection Report (EIR) within 24 hours of receipt.  The contractor shall include the USG in all scheduled meetings and teleconferences with regulatory agencies.

 

3.                            Under Section C, Description/Specifications, within C.1. STATEMENT OF WORK, the work statement is completely revised to incorporate changes and update the milestones.  As a result, C.1. paragraphs A. and B. are revised as follows:

 

A.            Independently, and not as an agent of the USG, the Contractor shall furnish all the necessary services, qualified personnel, materials, supplies, equipment, facilities, transportation and travel not otherwise provided by the USG as required to perform a revised Statement of Work and Contractor Defined Milestones, as set forth in Attachment #2, which is incorporated into this contract modification.

 

B.            CONTRACT OPTIONS

 

The Government may exercise any of the three remaining options for the continuation of requirements as set forth in the following Contractor Defined Milestones.  Exercise of each option also extends the contract’s period of performance by twelve months.  Option periods may be subject to renegotiation by the Parties depending on the current state of the art at the time of option exercise.  Additionally, Option #5 as stated below may be exercised at any time during Contract Performance.

 

SECTION C-DESCRIPTION/SPECIFICATIONS
 C.1.            Revised Statement of Work
 A.

 

	
Description exercised Base and Option #1
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

B.                      CONTRACT OPTIONS

 

	
Description Option #2
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

	
Description Option #3
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

	
Description Option #4
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    

 

	
Description Option #5
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    

 

4.                            The Contracting Officer designation in Section D, Packaging, Marking and Shipping, under the heading “Report Deliverables” is revised as follows:

 

[***]

 

5.                            Under Section G - Contract Administration Data, G.1. Project Officer, the Alternate Project Officer, [***] designation is revoked and replaced with [***] as noted below.  All references to “Project Officer” are revised to read “Contracting Officer Technical Representative.”

 

[***]

 

[***]
 [***] Office

 

6.                            [***]

 

[***]
 [***]

 

4

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

[***]

 

Each Party represents and warrants to the other Party that Mod 3’s terms, conditions, and forms of expressions were negotiated and bargained by and between the Parties.  Except for the Contract changes effectuated by Mod 3, each Contract term and condition survives Mod 3 unaltered, unaffected and in full force and effect.

 

[End of Modification No.3 and the remainder of this page intentionally left blank]

 

5

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A NO. 11.   THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS ~ The above numbered   solicitation is amended as set forth in Item 14. The hour and date specified   for receipt of Offers ~ is extended, ~ is not extended. Offers must   acknowledge receipt of this amendment prior to the hour and date specified in   the solicitation or as amended, by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of   this amendment, your desire to change an offer already submitted, such change   may be made by telegram or letter, provided each telegram or letter makes   reference to the solicitation and this amendment, and is received prior to   the opening hour and date specified. 12. ACCOUNTING AND APPROPRIATION DATA   (if required) Requisition # OS72587, Appr. Yr. 2011, CAN 1992002, Object   Class 265329 13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS,   IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14. FAR 17.207, FAR   1.602-1 and mutual agreement of the parties E. IMPORTANT: Contractor [ ]is   not, [X] is required to sign this document and return 2 copies to the issuing   office. 14. DESCRIPTION OF MODIFICATION PURPOSES: To exercise Option Period 2   Option Period 2 is exercised herewith based on the revised Period of   Performance beginning September 16, 2011, and ending November 15, 2012, for   the contract amount of $[***] No other terms or conditions are changed by   this modification. Funds Obligated: $[***] Total Contract Dollar Amount:   $[***] Contract Expiration Date: November 15, 2012 Except as provided herein,   all terms and conditions of the document referenced in Item 9A or 10A, as   heretofore changed, remains unchanged and in full force and effect. NSN   7540-01-152-8070 OMB No. 0990–0115 STANDARD FORM 30 (REV. 10-83)FAR (48 CFR)   53.243 123269097 v2 15A. NAME AND TITLE OF SIGNER (Type or print) [***],   EXECUTIVE VICE PRESIDENT 16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or   print) [***], Contracting Officer 15B. CONTRACTOR/OFFEROR /s/ [***]   (Signature of person authorized to sign) 15C. DATE SIGNED 12 Sep 011 16B.   UNITED STATES OF AMERICA BY /s/ [***] (Signature of Contracting Officer) 16C.   DATE SIGNED 16 Sep 2011 (Y) A.THIS CHANGE ORDER IS ISSUED PURSUANT TO:   (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT   ORDER NO. IN ITEM 10A. B.THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO   REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office,   appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF   FAR 43.103(b). Y C.THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO   AUTHORITY OF: D.OTHER (Specify type of modification and authority) AMENDMENT   OF SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE PAGE OF PAGES 1   1 2. AMENDMENT/MODIFICATION NO 4 3. EFFECTIVE DATE See Block 16C 4.   REQUISITION/PURC N/A 5. PROJECT NO. (If applicable) 6. ISSUED BYCODE 7.   ADMINISTERED BY (If other than Item 6)CODE HHS/ASPR/AMCG 330 Independence   Ave, SW Room G640 Washington, DC 20201 8. NAME AND ADDRESS OF CONTRACTOR   (No., street, county, State and ZIP Code) Bavarian Nordic A/S Hejreskovvej   10A 3490 Kvistgård Denmark (x) 9A. AMENDMENT OF SOLICITATION NO. 9B. DATED   (SEE ITEM 11) x 10A. MODIFICATION OF CONTRACT/ORDER HHSO100201000011C 10B.   DATED (SEE ITEM 13) November 16, 2009 CODE: FACILITY CODE: 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A   ADMINISTERED BY (IF OTHER THAN ITEM 6)CODE The above numbered solicitation is   amended as set forth in item 14. The hour and date specified for receipt of   Offers is extended is not extended. Offers must acknowledge receipt of this   amendment prior to the hour and date specified in the solicitation or as   amended by one of the following methods: (a) By completing Items 8 and 15,   and returning copies of the amendment; (b) By acknowledging receipt of this   amendment on each copy of the offer submitted; or (c) By separate letter or   telegram which includes a reference to the solicitation and amendment   numbers, FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED   FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN   REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change   an offer already submitted, such change may be made by telegram or letter,   provided each telegram or letter makes reference to the solicitation and this   amendment, and is received prior to the opening hour and date specified. NSN   7540-01-152-8070 Previous Edition Unusable STANDARD FORM 30 (REV. 10-83)   Prescribed by GSA FAR (48 CFR) 53.243 123269097 v2 12. ACCOUNTING AND   APPROPRIATION DATA (If Required) EIN:CAN:Appropriation:O.C.Obligation: 13.   THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS, IT MODIFIES THE   CONTRACT/ORDER NO., AS DESCRIBED IN ITEM 14 A. THIS CHANGE ORDER IS ISSUED   PURSUANT TO: (Specify Authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN   THE CONTRACT ORDER NO. IN ITEM 10A. B. THE ABOVE NUMBERED CONTRACT/ORDER IS   MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying   office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE   AUTHORITY OF FAR 43.103(b). C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO   PURSUANT TO AUTHORITY OF: FAR 1.602-1, FAR Mutual Agreement of the Parties   D.OTHER (Specify type of modification and authority) E. IMPORTANT: Contractoris   Notis required to sign this document and return 1 Copy to the issuing office.   14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings,   including solicitation/contract subject matter where feasible. The purpose of   this modification is to (1) to provide a three (3) year no cost extension to   the period of performance from November 15, 2012 to November 15, 2015 and (2)   transfer monies from CLIN 2 to CLIN 3. The cost to complete remains   unchanged. (See continuation Sheet) Except as provided herein, all terms and   conditions of the document referenced in Item 9A or 10A, as heretofore   changed, remains unchanged and in full force and effect. 15A. NAME AND TITLE   OF SIGNER [***], EVP 16A. NAME AND TITLE OF CONTRACTING OFFICER [***], Contracting   Officer 15B. CONTRACTOR/OFFEROR /s/ [***] (Signature of person authorized to   sign) 15C. DATE SIGNED 7 Nov 2012 16B. UNITED STATES OF AMERICA /s/ [***]   (Signature of Contracting Officer) 16C. DATE SIGNED 9 Nov 2012 AMENDMENT OF   SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE N/A Page 1 of 2 2.   AMENDMENT/MODIFICATION NO. Modification 005 3. EFFECTIVE DATE See Item 16C 4.   REQUISITION/PURCHASE REQ. NO. N/A 5. PROJECT NO. (If applicable) 6. ISSUED   BYCODE N/A 7. See N/A U.S. DEPT OF HEALTH & HUMAN SERVICES ASPR/BARDA 330   INDEPENDENCE AVE SW, ROOM G640 Washington, D.C. 20201 Item 6 8. NAME AND   ADDRESS OF CONTRACTOR (No., Street, County, State and Zip Code) Bavarian   Nordic A/S Hejreskovvej 10A DK-3490 Kvistgard Denmark 9A. AMENDMENT OF   SOLICITATION NO. 9B. DATED (SEE ITEM 11) 10A. MODIFICATION OF CONTRACT/ORDER   NO. HHSO100201000011C 10B. DATED (SEE ITEM 13) November 16, 2009 CODE: N/A   FACILITY CODE: N/A 11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Contract Number HHSO100201000011C
    	
 
    	
 
    
	
Modification No: 005
    	
 
    	
(continuation sheet)
    

 

	
Continuation   Sheet
    	
Contract   No: HHSO100201000011C
   Modification No: 5
    	
 
    

 

Modification No. 005 (the “Mod 5”) to Contract No. HHSO100201000011C, as amended to the date of Mod 5, (the “Existing Contract”) entered into and made effective as of the date imprinted in Block 16C of the Standard Form 30, is by and between the United States of America—which is represented by the Department of Health and Human Services, Biomedical Advanced Research and Development Authority—and Bavarian Nordic (“BN”), a company registered in Denmark, with a principal place of business located at Hejreskovvej 10 A, 3490, Kvistgard, Denmark, (USG and BN each being referred to as a “Party” and collectively as the “Parties”) who jointly agree to be bound by the terms and conditions hereof,

 

The base contract award is revised as follows:

 

1.              The contract’s expiration date is extended by three (3) years for a no cost extension. The revised expiration date for Section F. Deliverables and Performance, F.1. Period of Performance shall be November 15, 2015.

 

2.              The dollar amounts for the CLIN’s 0002 and 0003 are modified. Section B. Supplies or Services and Prices/Costs, A. CONTRACT LINE ITEM NUMBER (CLIN’S), 2. Contract Options are therefore modified as shown below:

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST.COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0002
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0003
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    

 

[End of Modification No. 5 and the remainder of this page intentionally left blank]

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A   ADMINISTERED BY (IF OTHER THAN ITEM 6)CODE The above numbered solicitation is   amended as set forth in item 14. The hour and date specified for receipt of   Offers is extended is not extended. Offers must acknowledge receipt of this   amendment prior to the hour and date specified in the solicitation or as   amended by one of the following methods: (a) By completing Items 8 and 15,   and returning copies of the amendment; (b) By acknowledging receipt of this   amendment on each copy of the offer submitted; or (c) By separate letter or   telegram which includes a reference to the solicitation and amendment   numbers, FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE   DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY   RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire   to change an offer already submitted, such change may be made by telegram or   letter, provided each telegram or letter makes reference to the solicitation   and this amendment, and is received prior to the opening hour and date   specified. NSN 7540-01-152-8070 Previous Edition Unusable STANDARD FORM 30   (REV. 10-83) Prescribed by GSA FAR (48 CFR) 53.243 123269097 v2 12.   ACCOUNTING AND APPROPRIATION DATA (If Required)   EIN:CAN:Appropriation:O.C.Obligation: 13. THIS ITEM APPLIES ONLY TO   MODIFICATIONS OF CONTRACTS/ORDERS, IT MODIFIES THE CONTRACT/ORDER NO., AS   DESCRIBED IN ITEM 14 A THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify   Authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO.   IN ITEM 10A B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE   ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date,   etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b). C.   THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF: FAR   1.602-1, FAR Mutual Agreement of the Parties D. OTHER (Specify type of   modification and authority) E. IMPORTANT: Contractoris NOTis required to sign   this document and return1Copy to the issuing office. 14. DESCRIPTION OF   AMENDMENT/MODIFICATION (Organized by UCF section headings, including   solicitation/contract subject matter where feasible. The purpose of this   modification is to (1) To incorporate a revised Statement of Work and   milestones. No other terms or conditions are change by this modification. See   continuation sheet. The cost to complete remains unchanged. (See continuation   Sheet) Except as provided herein, all terms and conditions of the document   referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in   full force and effect. 15A. NAME AND TITLE OF SIGNER [***], Executive Vice   President 16A. NAME AND TITLE OF CONTRACTING OFFICER [***], Contracting   Officer 15B. CONTRACTOR/OFFEROR /s/ [***] (Signature of person authorized to   sign) 15C. DATE SIGNED 2 May 2013 16B. UNITED STATES OF AMERICA /s/ [***]   (Signature of Contracting Officer) 16C. DATE SIGNED 5 May 2013 AMENDMENT OF   SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE N/A Page 1 of 3 2.   AMENDMENT/MODIFICATION NO. Modification 006 3. EFFECTIVE DATE See Item 16C 4.   REQUISITION/PURCHASE REQ. NO. N/A 5. PROJECT NO. (If applicable) 6. ISSUED   BYCODE N/A 7. See N/A U.S. DEPT OF HEALTH & HUMAN SERVICES ASPR/BARDA 330   INDEPENDENCE AVE SW, ROOM G640 Washington, D.C. 20201 Item 6 8. NAME AND   ADDRESS OF CONTRACTOR (No., Street, County, State and Zip Code) Bavarian   Nordic A/S Hejreskovvej 10A DK-3490 Kvistgard Denmark 9A. AMENDMENT OF   SOLICITATION NO 9B. DATED (SEE ITEM 11) 10A. MODIFICATION OF CONTRACT/ORDER   NO. HHSO100201000011C 10B. DATED (SEE ITEM 13) November 16, 2009 CODE: N/A   FACILITY CODE: N/A 11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Contract Number HHSO100201000011C
    	
 
    	
 
    
	
Modification No: 006
    	
 
    	
(continuation sheet)
    

 

	
Continuation   Sheet
    	
Contract No: HHSO100201000011C
   Modification No: 6
    	
 
    

 

Modification No. 006 (the “Mod_6”) to Contract No. HHSO100201000011C, as amended to the date of Mod-6, (the “Existing Contract”) entered into and made effective as of the date imprinted in Block 16C of the Standard Form 30, is by and between the United States of America—which is represented by the Department of Health and Human Services, Biomedical Advanced Research and Development Authority—and Bavarian Nordic (“BN”), a company registered in Denmark, with a principal place of business located at Hejreskovvej 10 A, 3490, Kvistgard, Denmark, (USG and BN each being referred to as a “Party” and collectively as the “Parties”) who jointly agree to be bound by the terms and conditions hereof.

 

The base contract award is revised as follows:

 

1.              As a result of revisions to the Statement of Work, the dollar amount for optional CLIN’s 0003, 0004, and 0005 are modified. Section B. Supplies or Services and Prices/Cost. A. CONTRACT LINE ITEM NUMEBR (CLINS), 2. Contract Options are therefore modified as shown below.

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0001
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0002
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0003
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0004
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
	
0005
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    

 

2.              Under Section C, Description/Specification within C.1. STATEMENT OF WORK, the work statement is completely revised to incorporate changes and update the milestones. The full written copy of the Statement of Work is included as Attachment I to this Modification.

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

REVISED - NEW MOD as April 2013

 

SECTION C - DESCRIPTION/SPECIFICATIONS

C.1. Revised Statement of Work

 

	
A.
    	
 
    	
CONTRACT BASE
    
	
 
    	
 
    	
 
    
	
Description exercised Base
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

	
B.
    	
 
    	
CONTRACT   OPTIONS
    
	
 
    	
 
    	
 
    
	
Description Option #1
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

	
Description Option #2
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

	
Description Option #3
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    

 

	
Description Option #4
    	
 
    	
SOW Section Number
    
	
[***]
    	
 
    	
[***]
    

 

[End of Modification No. 6 and the remainder of this page intentionally left blank]

 

3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A N/A The   above numbered solicitation is amended as set forth in item 14. The hour and   date specified for receipt of Offers is extended is not extended. Offers must   acknowledge receipt of this amendment prior to the hour and date specified in   the solicitation or as amended by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers, FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this   amendment you desire to change an offer already submitted, such change may be   made by telegram or letter, provided each telegram or letter makes reference   to the solicitation and this amendment, and is received prior to the opening   hour and date specified. 123269097 v2 12. ACCOUNTING AND APPROPRIATION DATA   (If Required) EIN:CAN:Appropriation:O.C.Obligation: 13. THIS ITEM APPLIES   ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS, IT MODIFIES THE CONTRACT/ORDER   NO., AS DESCRIBED IN ITEM 14 A.THIS CHANGE ORDER IS ISSUED PURSUANT TO:   (Specify Authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT   ORDER NO. IN ITEM 10A. B.THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO   REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office,   appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF   FAR 43.103(b). C.THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO   AUTHORITY OF: D.OTHER (Specify type of modification and authority) E.   IMPORTANT: Contractoris NOTis required to sign this document and return1Copy   to the issuing office. 14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized   by UCF section headings, including solicitation/contract subject matter where   feasible. The purpose of this modification is to (1) To update Section D – Packaging,   Marking, and Shipping and (2) to remove the requirement for one hard copy of   the monthly technical progress report and executive summary in Clause F2.   Technical Report Requirement. No other terms or conditions are change by this   modification. See continuation sheet. The cost to complete remains unchanged.   (See continuation Sheet) Except as provided herein, all terms and conditions   of the document referenced in Item 9A or 10A, as heretofore changed, remains   unchanged and in full force and effect. 15A. NAME AND TITLE OF SIGNER 16A.   NAME AND TITLE OF CONTRACTING OFFICER [***], Contracting Officer 15B.   CONTRACTOR/OFFEROR (Signature of person authorized to sign) 15C. DATE SIGNED   16B. UNITED STATES OF AMERICA /s/ [***] (Signature of Contracting Officer) 16C.   DATE SIGNED 9/24/13 AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT 1.   CONTRACT ID CODE Page 1 of 2 2. AMENDMENT/MODIFICATION NO. Modification 007   3. EFFECTIVE DATE See Item 16C 4. REQUISITION/PURCHASE REQ. NO. N/A 5.   PROJECT NO. (If applicable) 6. ISSUED BYCODE N/A 7. ADMINISTERED BY (IF OTHER   THAN ITEM 6) CODE N/A U.S. DEPT OF HEALTH & HUMAN SERVICES ASPR/BARDA 330   INDEPENDENCE AVE SW, ROOM G640 WASHINGTON, D.C. 20201 See Item 6 8. NAME AND   ADDRESS OF CONTRACTOR (No., Street, County, State and Zip Code) Bavarian   Nordic A/S Hejreskovvej 10A DK-3490 Kvistgard Denmark 9A. AMENDMENT OF   SOLICITATION NO. 9B. DATED (SEE ITEM 11) 10A. MODIFICATION OF CONTRACT/ORDER   NO. HHSO100201000011C 10B. DATED (SEE ITEM 13) November 16, 2009 CODE: N/A   FACILITY CODE: N/A 11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS NSN   7540-01-152-8070 Previous Edition Unusable STANDARD FORM 30 (REV. 10-83)   Prescribed by GSA FAR (48 CFR) 53.243 123269097 v2 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Contract Number HHSO100201000011C
    	
 
    	
 
    
	
Modification No: 007
    	
 
    	
(continuation sheet)
    

 

	
Continuation   Sheet
    	
Contract No: HHSO100201000011C
   Modification No:  7
    	
 
    

 

Modification No. 007 (the “Mod _7”) to Contract No. HHSO100201000011C, as amended to the date of Mod-7, (the “Existing Contract”) entered into and made effective as of the date imprinted in Block 16C of the Standard Form 30, is by and between the United States of America—which is represented by the Department of Health and Human Services, Biomedical Advanced Research and Development Authority—and Bavarian Nordic (“BN”), a company registered in Denmark, with a principal place of business located at Hejreskovvej 10 A, 3490, Kvistgard, Denmark, (USG and BN each being referred to as a “Party” and collectively as the “Parties”) who jointly agree to be bound by the terms and conditions hereof,

 

The base contract award is revised as follows:

 

SECTION D—PACKAGING, MARKING AND SHIPPING

 

Report Deliverables

 

Unless otherwise specified by the Contracting Officer or the Contracting Officer’s representative, delivery of reports to be furnished to the Government under this contract (including invoices), shall be addressed as follows:

 

[***]

[***]

[***]

[***]

[***]

[***]

[***]

 

[***]

[***]

[***]

[***]

[***]

[***]

 

F.2. TECHNICAL REPORT REQUIREMENT

 

	
Item
    	
 
    	
Deliverable
    	
 
    	
Quantity
    	
 
    	
Due Date
    
	
1.
    	
 
    	
Technical Monthly Progress Report and Executive   Summary
    	
 
    	
1 Electronic Copy —
   Project Officer (PO)
   1 Electronic Copy — Contracting Officer (CO)
    	
 
    	
30 days after contract award and by the 15th day of each month during the contract’s   period of performance. Not due when Final is due.
    

 

[End of Modification No. 7 and the remainder of this page intentionally left blank]

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A N/A The   above numbered solicitation is amended as set forth in item 14. The hour and   date specified for receipt of Offers is extended is not extended. Offers must   acknowledge receipt of this amendment prior to the hour and date specified in   the solicitation or as amended by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers, FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this   amendment you desire to change an offer already submitted, such change may be   made by telegram or letter, provided each telegram or letter makes reference   to the solicitation and this amendment, and is received prior to the opening   hour and date specified. NSN 7540-01-152-8070 Previous Edition Unusable   123269097 v2 STANDARD FORM 30 (REV. 10-83) Prescribed by GSA FAR (48 CFR)   53.243 12. ACCOUNTING AND APPROPRIATION DATA (If Required) EIN:CAN:   1992003Appropriation: 2014.1992003.25106Obligation: $[***] 13. THIS ITEM   APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS, IT MODIFIES THE   CONTRACT/ORDER NO., AS DESCRIBED IN ITEM 14 A. THIS CHANGE ORDER IS ISSUED   PURSUANT TO: (Specify Authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN   THE CONTRACT ORDER NO. IN ITEM 10A. B. THE ABOVE NUMBERED CONTRACT/ORDER IS   MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying   office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE   AUTHORITY OF FAR 43.103(b). C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO   PURSUANT TO AUTHORITY OF: 17.207, FAR 1.602-1 and mutual agreement of the   parties D. OTHER (Specify type of modification and authority) E. IMPORTANT:   Contractoris NOTis required to sign this document and return1Copy to the   issuing office. 14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF   section headings, including solicitation/contract subject matter where   feasible. The purpose of this modification is to (1) to modify dollar amounts   for Option 4 (CLIN 5), (2) to incorporate a SOW and milestones for this   option (3) exercise Option# 4 (CLIN 5) based on the revised dollar amount.   Please note, BARDA must review and approve all protocols prior to study   initiation. No other terms or conditions are change by this modification. See   continuation sheet. Funds Obligated: $[***] (See continuation Sheet) Except   as provided herein, all terms and conditions of the document referenced in   Item 9A or 10A, as heretofore changed, remains unchanged and in full force   and effect. 15A. NAME AND TITLE OF SIGNER [***] Executive Vice President 16A.   NAME AND TITLE OF CONTRACTING OFFICER [***], Contracting Officer 15B.   CONTRACTOR/OFFEROR /s/ [***] (Signature of person authorized to sign) 15C.   DATE SIGNED 17, April 2014 16B. UNITED STATES OF AMERICA /s/ [***] (Signature   of Contracting Officer) 16C. DATE SIGNED 4/17/14 AMENDMENT OF   SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE Page 1 of 21 2.   AMENDMENT/MODIFICATION NO. Modification 008 3. EFFECTIVE DATE See Item 16C 4.   REQUISITION/PURCHASE REQ. NO. OS130852 5. PROJECT NO. (If applicable) 6.   ISSUED BYCODE N/A 7. ADMINISTERED BY (IF OTHER THAN ITEM 6) CODE N/A U.S.   DEPT OF HEALTH & HUMAN SERVICES ASPR/BARDA 330 INDEPENDENCE AVE SW, ROOM   G640 WASHINGTON, D.C. 20201 See Item 6 8. NAME AND ADDRESS OF CONTRACTOR (No.,   Street, County, State and Zip Code) Bavarian Nordic A/S Hejreskovvej 10A   DK-3490 Kvistgard Denmark 9A. AMENDMENT OF SOLICITATION NO. 9B. DATED (SEE   ITEM 11) 10A. MODIFICATION OF CONTRACT/ORDER NO. HHSO100201000011C 10B. DATED   (SEE ITEM 13) November 16, 2009 CODE: N/A FACILITY CODE: N/A 11. THIS ITEM   ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Contract Number HHSO100201000011C
    	
 
    	
 
    
	
Modification No: 008
    	
 
    	
(continuation sheet)
    

 

	
Continuation   Sheet
    	
Contract No: HHSO100201000011C
   Modification No:  8
    	
 
    

 

Modification No. 008 (the “Mod _8”) to Contract No. HHSO100201000011C, as amended to the date of Mod-8, (the “Existing Contract”) entered into and made effective as of the date imprinted in Block 16C of the Standard Form 30, is by and between the United States of America—which is represented by the Department of Health and Human Services, Biomedical Advanced Research and Development Authority—and Bavarian Nordic (“BN”), a company registered in Denmark, with a principal place of business located at Hejreskovvej 10 A, 3490, Kvistgard, Denmark, (USG and BN each being referred to as a “Party” and collectively as the “Parties”) who jointly agree to be bound by the terms and conditions hereof,

 

The base contract award is revised as follows:

 

1.              As a result of revisions to the Statement of Work, the dollar amount for optional CLIN 0005 is modified. Section B. Supplies or Services and Prices/Cost, A. CONTRACT LINE ITEM NUMEBR (CLINS), 2. Contract Option is therefore modified as shown below.

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0005
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
													

 

2.              Under Section C. Description/Specification within C.1. STATEMENT OF WORK, the work statement is revised to include a SOW for this option and milestone activities have been added. The full written copy of the Statement of Work for Option #4 is included as Attachment 1 to this Modification. Below is the updated milestones

 

	
Activity
    	
 
    	
Milestone
    	
 
    	
Completion Date
    
	
[***]
    	
 
    	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    	
 
    	
[***]
    

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

3.              Contract Option #4 is hereby exercised at an increased amount. The revised and exercised Option # 4 amount is shown below.

 

	
CLIN’s
    	
 
    	
DESCRIPTION
    	
 
    	
EST. COST
    	
 
    	
FIXED FEE
    	
 
    	
TOTAL
   EST. CPFF
    	
 
    
	
0005
    	
 
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    	
$
    	
[***]
    	
 
    
													

 

[End of Modification No. 8 and the remainder of this page intentionally left blank]

 

3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A N/A The   above numbered solicitation is amended as set forth in item 14. The hour and   date specified for receipt of Offers is extended is not extended. Offers must   acknowledge receipt of this amendment prior to the hour and date specified in   the solicitation or as amended by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers, FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this   amendment you desire to change an offer already submitted, such change may be   made by telegram or letter, provided each telegram or letter makes reference   to the solicitation and this amendment, and is received prior to the opening   hour and date specified. NSN 7540-01-152-8070 Previous Edition Unusable   STANDARD FORM 30 (REV. 10-83) Prescribed by GSA FAR (48 CFR) 53.243 123269097   v2 12. ACCOUNTING AND APPROPRIATION DATA (If Required)   EIN:CAN:Appropriation:O.C.Obligation: 13. THIS ITEM APPLIES ONLY TO MODIFICATIONS   OF CONTRACTS/ORDERS, IT MODIFIES THE CONTRACT/ORDER NO., AS DESCRIBED IN ITEM   14 A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify Authority) THE   CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO. IN ITEM 10A.   B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE   ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date,   etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b). C.   THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF: D.   OTHER (Specify type of modification and authority) E. IMPORTANT: Contractoris   NOTis required to sign this document and return1Copy to the issuing office.   14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings,   including solicitation/contract subject matter where feasible. The purpose of   this modification is to (1) To update clause G.2. – Key Personnel. No other   terms or conditions are change by this modification. See continuation sheet.   The cost to complete remains unchanged. (See continuation Sheet) Except as   provided herein, all terms and conditions of the document referenced in Item   9A or 10A, as heretofore changed, remains unchanged and in full force and   effect. 15A. NAME AND TITLE OF SIGNER 16A. NAME AND TITLE OF CONTRACTING   OFFICER [***], Contracting Officer 15B. CONTRACTOR/OFFEROR (Signature of   person authorized to sign) 15C. DATE SIGNED 16B. UNITED STATES OF AMERICA /s/   [***] (Signature of Contracting Officer) 16C. DATE SIGNED 4 Nov 2014   AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE Page 1   of 2 2. AMENDMENT/MODIFICATION NO. Modification 009 3. EFFECTIVE DATE See   Item 16C 4. REQUISITION/PURCHASE REQ. NO. N/A 5. PROJECT NO. (If applicable)   6. ISSUED BYCODE N/A 7. ADMINISTERED BY (IF OTHER THAN ITEM 6) CODE N/A U.S.   DEPT OF HEALTH & HUMAN SERVICES ASPR/BARDA 330 INDEPENDENCE AVE SW, ROOM   G640 WASHINGTON, D.C. 20201 See Item 6 8. NAME AND ADDRESS OF CONTRACTOR   (No., Street, County, State and Zip Code) Bavarian Nordic A/S Hejreskovvej   10A DK-3490 Kvistgard Denmark 9A. AMENDMENT OF SOLICITATION NO. 9B. DATED   (SEE ITEM 11) 10A. MODIFICATION OF CONTRACT/ORDER NO. HHSO100201000011C 10B.   DATED (SEE ITEM 13) November 16, 2009 CODE: N/A FACILITY CODE: N/A 11. THIS   ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Contract Number HHSO100201000011C
    	
 
    	
 
    
	
Modification No: 009
    	
 
    	
(continuation sheet)
    

 

	
Continuation   Sheet
    	
Contract No:    HHSO100201000011C
   Modification No:  9
    	
 
    

 

The base contract award is revised as follows:

 

G.2. KEY PERSONNEL

 

Pursuant to the Key Personnel clause incorporated in Section I of this contract, the following individual is considered to be essential to the work being performed hereunder:

 

[***]

 

Prior to diverting any of the specific individuals to other programs, the Contractor shall notify the Contacting officer
  reasonably in advance and shall submit justification (including proposed substitutions) in sufficient detail to permit evaluation of the impact on the program. No diversion shall be made by the contractor without the written consent of the Contracting Officer; provided that the Contracting Officer may ratify in writing such diversion and such ratification shall constitute the consent of the Contracting Officer. The contract may be modified from time to time during the course of the contract to either add or delete personnel, as appropriate.

 

[End of Modification No. 9 and the remainder of this page intentionally left blank]

 

2

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

N/A N/A The   above numbered solicitation is amended as set forth in item 14. The hour and   date specified for receipt of Offers is extended is not extended. Offers must   acknowledge receipt of this amendment prior to the hour and date specified in   the solicitation or as amended by one of the following methods: (a) By   completing Items 8 and 15, and returning copies of the amendment; (b) By   acknowledging receipt of this amendment on each copy of the offer submitted;   or (c) By separate letter or telegram which includes a reference to the   solicitation and amendment numbers, FAILURE OF YOUR ACKNOWLEDGMENT TO BE   RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR   AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this   amendment you desire to change an offer already submitted, such change may be   made by telegram or letter, provided each telegram or letter makes reference   to the solicitation and this amendment, and is received prior to the opening   hour and date specified. (Signature of Contracting Officer) NSN   7540-01-152-8070 123269097 v2 STANDARD FORM 30 (REV. 10-83) 12. ACCOUNTING   AND APPROPRIATION DATA (If Required) EIN:CAN:Appropriation:O.C.Obligation:   13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS, IT MODIFIES   THE CONTRACT/ORDER NO., AS DESCRIBED IN ITEM 14 A. THIS CHANGE ORDER IS   ISSUED PURSUANT TO: (Specify Authority) THE CHANGES SET FORTH IN ITEM 14 ARE   MADE IN THE CONTRACT ORDER NO. IN ITEM 10A. B. THE ABOVE NUMBERED   CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as   changes in paying office, appropriation date, etc.) SET FORTH IN ITEM 14,   PURSUANT TO THE AUTHORITY OF FAR 43.103(b). C. THIS SUPPLEMENTAL AGREEMENT IS   ENTERED INTO PURSUANT TO AUTHORITY OF: D. OTHER (Specify type of modification   and authority) E. IMPORTANT: Contractoris NOTis required to sign this   document and return1Copy to the issuing office. 14. DESCRIPTION OF   AMENDMENT/MODIFICATION (Organized by UCF section headings, including   solicitation/contract subject matter where feasible.) The purpose of this   modification is to (1) to provide a one (1) year no cost extension to the   period of performance from November 15, 2015 to November 15, 2016 and (2)   update G.3. Invoice/Financing Request and Contract Financial Reporting. No   other terms or conditions are change by this modification. See continuation   sheet. The cost to complete remains unchanged. Contract Expiration Date:   November 15, 2016 (See continuation Sheet) Except as provided herein, all   terms and conditions of the document referenced in Item 9A or 10A, as   heretofore changed, remains unchanged and in full force and effect. 15A. NAME   AND TITLE OF SIGNER[***] [***], Director of Finance 16A. NAME AND TITLE OF   CONTRACTING OFFICER [***], Contracting Officer 15B. CONTRACTOR/OFFEROR /s/   [***] (Signature of person authorized to sign) 15C. DATE SIGNED Mar-19-2015   16B. UNITED STATES OF AMERICA /s/ [***] 16C. DATE SIGNED AMENDMENT OF   SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE Page 1 of 2 2.   AMENDMENT/MODIFICATION NO. Modification 010 3. EFFECTIVE DATE See Item 16C 4.   REQUISITION/PURCHASE REQ. NO. N/A 5. PROJECT NO. (If applicable) 6. ISSUED   BYCODE N/A 7. ADMINISTERED BY (IF OTHER THAN ITEM 6) CODE N/A U.S. DEPT OF   HEALTH & HUMAN SERVICES ASPR/BARDA 330 INDEPENDENCE AVE SW, ROOM G640   WASHINGTON, D.C. 20201 See Item 6 8. NAME AND ADDRESS OF CONTRACTOR (No.,   Street, County, State and Zip Code) 9A. AMENDMENT OF SOLICITATION NO.   Bavarian Nordic A/S Hejreskovvej 10A DK-3490 Kvistgard Denmark 9B. DATED (SEE   ITEM 11) 10A. MODIFICATION OF CONTRACT/ORDER NO. HHSO100201000011C 10B. DATED   (SEE ITEM 13) November 16, 2009 CODE: N/A FACILITY CODE: N/A 11. THIS ITEM   ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS Previous Edition Unusable   Prescribed by GSA FAR (48 CFR) 53.243 123269097 v2 

    

 

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

	
Contract Number HHSO100201000011C
    	
 
    	
 
    
	
Modification No: 009
    	
 
    	
(continuation sheet)
    

 

	
Continuation   Sheet
    	
Contract No: HHSO100201000011C
   Modification No: 10
    	
 
    

 

The base contract award is revised as follows:

 

G.3. INVOICE/FINANCING REQUEST AND CONTRACT FINANCIAL REPORTING

 

1) Documents should be delivered electronically to the Contracting Officer (CO), the Contracting Officer’s Representative (COR) and PSC electronically.  Unless otherwise specified by the Contracting Officer all deliverables and reports furnished to the Government under the resultant contract (including invoices) shall be addressed as follows:

 

	
[***]
    	
 
    	
[***]
    	
 
    	
Email invoices to:
    
	
[***]
    	
 
    	
[***]
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    	
 
    	
[***]
    
	
[***]
    	
 
    	
[***]
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    	
 
    	
 
    
	
[***]
    	
 
    	
[***]
    	
 
    	
 
    

 

2)  Contractor invoices/financial reports shall conform to the form, format, and content requirements of the instructions for Invoice/Financing requests and Contract Financial Reporting made a part of the contract in Section J.

 

3)  Monthly invoices must include the cumulative total expenses to date, adjusted (as applicable) to show any amounts suspended by the Government.

 

4)  The contractor agrees to immediately notify the Contracting Officer in writing if there is an anticipated overrun (any amount) or unexpended balance (greater than 10 percent) of the amount allotted to the contract, and the reasons for the variance.  Also refer to the requirements of the Limitation of Cost (FAR 52.232-20) clause in the contract.

 

5)  The date of receipt of a proper invoice/voucher by the Contracting Officer shall be used for the purpose of Prompt
  Payment Act time computations.

 

[End of Modification No. 10 and the remainder of this page intentionally left blank]

 

2Exhibit 10.3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

PUBLIC HEALTH SERVICE

 

COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT
 FOR EXTRAMURAL-PHS CLINICAL RESEARCH

 

This Agreement is based on the model Cooperative Research and Development Agreement (“CRADA”) adopted by the U.S. Public Health Service (“PHS”) Technology Transfer Policy Board for use by components of the National Institutes of Health (“NIH”), the Centers for Disease Control and Prevention (“CDC”), and the Food and Drug Administration (“FDA”), which are agencies of the PHS within the Department of Health and Human Services (“HHS”).

 

This Cover Page identifies the Parties to this CRADA:

 

The U.S. Department of Health and Human Services, as represented by 
 the National Cancer Institute
  an Institute, Center, or Division (hereinafter referred to as the “ICD”) of the 
  National Institutes of Health

 

and

 

BN ImmunoTherapeutics,
 hereinafter referred to as the “Collaborator”,
 having offices at 2425 Garcia Avenue, Mountain View, CA 94043,
 created and operating under the laws of Delaware

 

 

COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

FOR EXTRAMURAL-PHS CLINICAL RESEARCH

 

Article 1.               Introduction

 

This CRADA between ICD and Collaborator will be effective when signed by the Parties, which are identified on both the Cover Page and the Signature Page (page 22).  The official contacts for the Parties are identified on the Contacts Information Page (page 23).  Publicly available information regarding this CRADA appears on the Summary Page (page 24).  The research and development activities that will be undertaken by ICD, ICD’s contractors or grantees, and Collaborator in the course of this CRADA are detailed in the Research Plan, attached as Appendix A. The staffing, funding, and materials contributions of the Parties are set forth in Appendix B. Any changes to the model CRADA are set forth in Appendix C.

 

Article 2.               Definitions

 

The terms listed in this Article will carry the meanings indicated throughout the CRADA. To the extent a definition of a term as provided in this Article is inconsistent with a corresponding definition in the applicable sections of either the United States Code (U.S.C.) or the Code of Federal Regulations (C.F.R.), the definition in the U.S.C. or C.F.R. will control.

 

“Adverse Drug Experience” or “ADE” means an Adverse Event associated with the use of the Test Article, that is, an event where there is a reasonable possibility that the Test Article may have caused the event (a relationship between the Test Article and the event cannot be ruled out), in accordance with the definitions of 21 C.F.R. Part 310, 305, or 312, or other applicable regulations.

 

“Adverse Event” or “AE” means any untoward medical occurrence in a Human Subject administered Test Article.  An AE does not necessarily have a causal relationship with the Test Article, that is, it can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the Test Article, whether or not it is related to it.  See FDA Good Clinical Practice Guideline (International Conference on Harmonisation (ICH) E6: “Good Clinical Practice: Consolidated Guidance, 62 Federal Register 25, 691 (1997)).

 

“Affiliate” means any corporation or other business entity controlled by, controlling, or under common control with Collaborator at any time during the term of the CRADA. For this purpose, “control” means direct or indirect beneficial ownership of at least fifty percent (50%) of the voting stock or at least fifty percent (50%) interest in the income of the corporation or other business entity.

 

“Annual Report” means the report of progress of an IND-associated investigation that the Sponsor must submit to the FDA within sixty (60) days of the anniversary of the effective date of the IND (pursuant to 21 C.F.R. § 312.33).

 

	
PHS ECT-CRADA
    	
 
    	
Case Ref.   No.        
    	
 
    	
MODEL ADOPTED 2005
    
	
 
    	
 
    	
 
    	
 
    	
Confidential
    

 

2

 

“Background Invention” means an Invention conceived and first actually reduced to practice before the Effective Date.

 

“Clinical Data in ICD’s Possession and Control” means all Raw Data that ICD employees create directly; and all copies of Raw Data and Summary Data that ICD obtains from Clinical Investigators or contractors performing CRADA activities.

 

“Clinical Investigator” means, in accordance with 21 C.F.R. § 312.3, an individual who actually conducts a clinical investigation, that is, who directs the administration or dispensation of Test Article to a subject, and who assumes responsibility for studying Human Subjects, for recording and ensuring the integrity of research data, and for protecting the welfare and safety of Human Subjects.

 

“Clinical Research Site(s)” means the site(s) at which the Protocol(s) described in the Research Plan will be performed.

 

“Collaborator Materials” means all tangible materials not first produced in the performance of this CRADA that are owned or controlled by Collaborator and used in the performance of the Research Plan.  The term “Collaborator Materials” does not include “Test Article” (defined below).

 

“Confidential Information” means confidential scientific, business, financial information, or Identifiable Private Information provided that Confidential Information does not include:

 

(a)         information that is publicly known or that is available from public sources;

 

(b)         information that has been made available by its owner to others without a confidentiality obligation;

 

(c)          information that is already known by the receiving Party, or information that is independently created or compiled by the receiving Party without reference to or use of the provided information; or

 

(d)         information that relates to potential hazards or cautionary warnings associated with the production, handling, or use of the subject matter of the Research Plan.

 

“Cooperative Research and Development Agreement” or “CRADA” means this Agreement, entered into pursuant to the Federal Technology Transfer Act of 1986, as amended (15 U.S.C. §§ 3710a et seq.), and Executive Order 12591 of April 10, 1987.

 

“CRADA Data” means information developed by or on behalf of the Parties in the performance of the Research Plan, excluding Raw Data.

 

“CRADA Materials” means all tangible materials first produced in the performance of the Research Plan other than CRADA Data.

 

	
PHS ECT-CRADA
    	
 
    	
Case Ref.   No.        
    	
 
    	
MODEL ADOPTED 2005
    
	
 
    	
 
    	
 
    	
 
    	
Confidential
    

 

3

 

“CRADA Principal Investigator(s)” or “CRADA PI(s)” means the person(s) designated by the Parties who will be responsible for the scientific and technical conduct of the Research Plan.

 

“CRADA Subject Invention” means any Invention of either or both Parties, conceived or first actually reduced to practice in the performance of the Research Plan.

 

“Drug Master File” or “DMF” is described in 21 C.F.R. Part 314.420.  A DMF is a submission to the FDA that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs.

 

“Effective Date” means the date of the last signature of the Parties executing this Agreement.

 

“Government” means the Government of the United States of America.

 

“Human Subject” means, in accordance with the definition in 45 C.F.R. § 46.102(f), a living individual about whom an investigator conducting research obtains:

 

(a)         data through intervention or interaction with the individual; or

 

(b)         Identifiable Private Information.

 

“ICD Materials” means all tangible materials not first produced in the performance of this CRADA that are owned or controlled by ICD and used in the performance of the Research Plan.

 

“IND” means an “Investigational New Drug Application,” filed in accordance with 21 C.F.R. Part 312 under which clinical investigation of an experimental drug or biologic (Test Article) is performed in Human Subjects in the United States or intended to support a United States licensing action.

 

“Identifiable Private Information” or “IPI” about a Human Subject means private information from which the identity of the subject is or may readily be ascertained.  Regulations defining and governing this information include 45 C.F.R. Part 46 and 21 C.F.R. Part 50.

 

“Institutional Review Board” or “IRB” means, in accordance with 45 C.F.R. Part 46, 21 C.F.R. part 56, and other applicable regulations, an independent body comprising medical, scientific, and nonscientific members, whose responsibility is to ensure the protection of the rights, safety, and well-being of the Human Subjects involved in a study.

 

	
PHS ECT-CRADA
    	
 
    	
Case Ref.   No.        
    	
 
    	
MODEL ADOPTED 2005
    
	
 
    	
 
    	
 
    	
 
    	
Confidential
    

 

4

 

“Invention” means any invention or discovery that is or may be patentable or otherwise protected under Title 35 of the United States Code, or any novel variety of plant which is or may be protectable under the Plant Variety Protection Act, 7 U.S.C. §§ 2321 et seq.

 

“Investigator’s Brochure” means, in accordance with the definition in 21 C.F.R. § 312.23(a)(5), a document containing information about the Test Article, including animal screening, preclinical toxicology, and detailed pharmaceutical data, including a description of possible risks and side effects to be anticipated on the basis of prior experience with the drug or related drugs, and precautions, such as additional monitoring, to be taken as part of the investigational use of the drug.

 

“Patent Application” means an application for patent protection for a CRADA Subject Invention with the United States Patent and Trademark Office (“U.S.P.T.O.”) or the corresponding patent-issuing authority of another nation.

 

“Patent” means any issued United States patent, any international counterpart(s), and any corresponding grant(s) by a non-U.S. government in place of a patent.

 

“Placebo” means an inactive substance identical in appearance to the material being tested that is used to distinguish between drug action and suggestive effect of the material under study.

 

“Protocol” means the formal, detailed description of a study to be performed as provided for in the Research Plan.  It describes the objective(s), design, methodology, statistical considerations, and organization of a trial.  For the purposes of this CRADA, the term, Protocol, for clinical research involving Human Subjects, includes any and all associated documents, including informed consent forms, to be provided to Human Subjects and potential participants in the study.

 

“Raw Data” means the primary quantitative and empirical data first collected from experiments and clinical trials conducted within the scope of this CRADA.

 

“Research Plan” means the statement in Appendix A of the respective research and development commitments of the Parties.  The Research Plan should describe the provisions for sponsoring the IND, clinical and safety monitoring, and data management.

 

“Sponsor” means, in accordance with the definition in 21 C.F.R. § 312.3, an organization or individual who assumes legal responsibility for supervising or overseeing clinical trials with Test Articles, and is sometimes referred to as the IND holder.

 

“Steering Committee” means the research and development team whose composition and responsibilities with regard to the research performed under this CRADA are described in Appendix A.

 

	
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“Summary Data” means any extract or summary of the Raw Data, generated either by or, on behalf of, ICD or by, or on behalf of, Collaborator.  Summary Data may include extracts or summaries that incorporate IPI.

 

“Test Article” means, in accordance with 21 C.F.R. § 50.3(j), any drug (including a biological product), medical device, food additive, color additive, electronic product, or any other article subject to regulation under the Federal Food, Drug, and Cosmetic Act that is intended for administration to humans or animals, including a drug or biologic as identified in the Research Plan and Appendix B, that is used within the scope of the Research Plan.  The Test Article may also be referred to as Investigational Agent, Study Material, or Study Product.

 

Article 3.               Cooperative Research and Development

 

3.1          Performance of Research and Development.  The research and development activities to be carried out under this CRADA will be performed by the Parties identified on the Cover Page, as well as ICD’s contractors or grantees as described in the Research Plan.  However, ICD’s contractors or grantees are not Parties to the CRADA, and this CRADA does not grant to Collaborator any rights to Inventions made by ICD’s contractors or grantees.  The CRADA PIs will be responsible for coordinating the scientific and technical conduct of this project on behalf of their employers.  Any Collaborator employees who will work at ICD facilities will be required to sign a Guest Researcher or Special Volunteer Agreement appropriately modified in view of the terms of this CRADA.

 

3.2          Research Plan.  The Parties recognize that the Research Plan describes the collaborative research and development activities they will undertake and that interim research goals set forth in the Research Plan are good faith guidelines.  Should events occur that require modification of these goals, then by mutual agreement the Parties can modify them through an amendment, according to Paragraph 13.6.

 

3.3          Use and Disposition of Collaborator Materials and ICD Materials.  The Parties agree to use Collaborator Materials and ICD Materials only in accordance with the Research Plan and Protocol(s), not to transfer these materials to third parties except in accordance with the Research Plan and Protocol(s) or as approved by the owning or providing Party, and, upon expiration or termination of the CRADA, to dispose of these materials as directed by the owning or providing Party.

 

3.4          Third-Party Rights in Collaborator’s CRADA Subject Inventions.  If Collaborator has received (or will receive) support of any kind from a third party in exchange for rights in any of Collaborator’s CRADA Subject Inventions, Collaborator agrees to ensure that its obligations to the third party are both consistent with Articles 6 through 8 and subordinate to Article 7 of this CRADA.

 

	
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3.5          Disclosures to ICD.  Prior to execution of this CRADA, Collaborator agrees to disclose to ICD all instances in which outstanding royalties are due under a PHS license agreement and in which Collaborator had a PHS license terminated in accordance with 37 C.F.R. § 404.10.  These disclosures will be treated as Confidential Information upon request by Collaborator in accordance with Paragraphs 2.4, 8.3, and 8.4.

 

3.6          Clinical Investigator Responsibilities.  The Clinical Investigator will be required to submit, or to arrange for submission of, each Protocol associated with this CRADA to all appropriate IRBs, and for ensuring that the IRBs are notified of the role of Collaborator in the research.  In addition to the Protocol all associated documents, including informational documents and advertisements, must be reviewed and approved by the appropriate IRB(s) before starting the research at each Clinical Research Site.  The research will be done in strict accordance with the Protocol(s) and no substantive changes in a finalized Protocol will be made unless mutually agreed upon, in writing, by the Parties.  Research will not commence (or will continue unchanged, if already in progress) until each substantive change to a Protocol, including those required by either the FDA or the IRB, has been integrated in a way acceptable to the Parties, submitted to the FDA (if applicable) and approved by the appropriate IRBs.

 

3.7          Investigational Applications.

 

3.7.1                     If an IND is required either ICD or Collaborator, as indicated in the Research Plan, will submit an IND and all Clinical Investigators must have completed registration documents on file (1572 forms).

 

3.7.2                     If ICD elects to file its own IND, Collaborator agrees to provide ICD background data and information necessary to support the IND. Collaborator further agrees to provide a letter of cross-reference to all pertinent regulatory filings sponsored by Collaborator.  Collaborator’s employees will be reasonably available to respond to inquiries from the FDA regarding information and data contained in the Collaborator’s IND, DMF, other filings, or other information and data provided to ICD by the Collaborator pursuant to this Article 3.  If ICD has provided information or data to assist Collaborator in its IND filing, ICD will provide a letter of cross reference to its IND and respond to inquiries related to information provided by ICD, as applicable.

 

3.7.3                     If Collaborator supplies Confidential Information to ICD in support of an IND filed by ICD, this information will be protected in accordance with the corresponding confidentiality provisions of Article 8.

 

3.7.4                     Collaborator may sponsor its own clinical trials and hold its own IND for studies performed outside the scope of this CRADA. These studies, however, should not adversely affect the ability to accomplish the goal of the Research Plan, for example, by competing for the same study population.  All data from those clinical trials are proprietary to Collaborator for purposes of this CRADA.

 

	
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3.8          Test Article Information and Supply.  Collaborator agrees to provide ICD without charge and on a schedule that will ensure adequate and timely performance of the research, a sufficient quantity of formulated and acceptably labeled, clinical-grade Test Article (and, as required by the Protocol(s), Placebo) to complete the clinical trial(s) agreed to and approved under this CRADA. Collaborator will provide a Certificate of Analysis to ICD for each lot of the Test Article provided.

 

3.9          Test Article Delivery and Usage.  Collaborator will ship the Test Article and, if required, Placebo to ICD or its designee in containers marked in accordance with 21 C.F.R. § 312.6.  ICD agrees that the Clinical Investigators will keep appropriate records and take reasonable steps to ensure that the Test Article is used in accordance with the Protocol(s) and applicable FDA regulations.  In addition, ICD agrees that the Test Article (and all Confidential Information supplied by Collaborator relating to the Test Article) will be used solely for the conduct of the CRADA research and development activities.  Furthermore, ICD agrees that no analysis or modification of the Test Article will be performed without Collaborator’s prior written consent.  At the completion of the Research Plan, any unused quantity of Test Article will be returned to Collaborator or disposed as directed by Collaborator.  Pharmacy contacts at ICD or its designee will be determined by ICD and communicated to Collaborator.

 

3.10        Monitoring.

 

3.10.1              The Sponsor or its designee will be primarily responsible for monitoring clinical sites and for assuring the quality of all clinical data, unless otherwise stated in the Research Plan.  Monitoring will comply with FDA Good Clinical Practice (International Conference on Harmonisation (ICH) E6: “Good Clinical Practice: Consolidated Guidance; 62 Federal Register 25, 691 (1997)).  The other Party may also perform quality assurance oversight.  The monitor will communicate significant Protocol violations and submit documentation of monitoring outcomes on Protocol insufficiencies to the other Party in a timely manner.

 

3.10.2              Subject to the restrictions in Article 8 concerning IPI, and with reasonable advance notice and at reasonable times, ICD will permit Collaborator or its designee(s) access to clinical site(s) to monitor the conduct of the research, as well as to audit source documents containing Raw Data, to the extent necessary to verify compliance with FDA Good Clinical Practice and the Protocol(s).

 

3.11        FDA Meetings/Communications.  All meetings with the FDA concerning any clinical trial within the scope of the Research Plan will be discussed by Collaborator and ICD in advance.  Each Party reserves the right to take part in setting the agenda for, to attend, and to participate in these meetings.  The Sponsor will provide the other Party with copies of FDA meeting minutes, all transmittal letters for IND submissions, IND safety reports, formal questions and responses that have been submitted to the FDA, Annual Reports, and official FDA correspondence, pertaining either to the INDs under this CRADA or to the Clinical Investigators on Protocols performed in accordance with the Research Plan, except to the extent that those documents contain the proprietary information of a third party or dissemination is prohibited by law.

 

	
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Article 4.               Reports

 

4.1          Interim Research and Development Reports.  The CRADA PIs should exchange information regularly, in writing.  This exchange may be accomplished through meeting minutes, detailed correspondence, circulation of draft manuscripts, Steering Committee reports, copies of Annual Reports and any other reports updating the progress of the CRADA research.  However, the Parties must exchange updated Investigator’s Brochure, formulation and preclinical data, and toxicology findings, as they become available.

 

4.2          Final Research and Development Reports.  The Parties will exchange final reports of their results within six (6) months after the expiration or termination of this CRADA. These reports will set forth the technical progress made; any publications arising from the research; and the existence of invention disclosures of potential CRADA Subject Inventions and/or any corresponding Patent Applications.

 

4.3          Fiscal Reports.  If Collaborator has agreed to provide funding to ICD under this CRADA and upon the request of Collaborator, then concurrent with the exchange of final research and development reports according to Paragraph 4.2, ICD will submit to Collaborator a statement of all costs incurred by ICD for the CRADA. If the CRADA has been terminated, ICD will specify any costs incurred before the date of termination for which ICD has not received funds from Collaborator, as well as for all reasonable termination costs including the cost of returning Collaborator property or removal of abandoned Collaborator property, for which Collaborator will be responsible.

 

4.4          Safety Reports.  In accordance with FDA requirements, the Sponsor will establish and maintain records and submit safety reports to the FDA, as required by 21 C.F.R. § 312.32 and 21 C.F.R. 812.150(b)(1), or other applicable regulations.  In the conduct of research under this CRADA, the Parties will comply with specific ICD guidelines and policies for reporting ADEs and AEs, as well as procedures specified in the Protocol(s).  The Sponsor must provide the other Party with copies of all Safety Reports concurrently with their submission to the FDA, and with any other information affecting the safety of Human Subjects in research conducted under this CRADA.

 

4.5          Annual Reports.  The Sponsor will provide the other Party a copy of the Annual Report concurrently with the submission of the Annual Report to the FDA. Annual Reports will be kept confidential in accordance with Article 8.

 

Article 5.               Staffing, Financial, and Materials Obligations

 

5.1          ICD and Collaborator Contributions.  The contributions of any staff, funds, materials, and equipment by the Parties are set forth in Appendix B. The Federal Technology Transfer Act of 1986, 15 U.S.C. § 3710a(d)(1) prohibits ICD from providing funds to Collaborator for any 

 

	
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research and development activities under this CRADA.

 

5.2          ICD Staffing.  No ICD employees will devote 100% of their effort or time to the research and development activities under this CRADA. ICD will not use funds provided by Collaborator under this CRADA for ICD personnel to pay the salary of any permanent ICD employee.  Although personnel hired by ICD using CRADA funds will focus principally on CRADA research and development activities, Collaborator acknowledges that these personnel may nonetheless make contributions to other research and development activities, and the activities will be outside the scope of this CRADA.

 

5.3          Collaborator Funding.  Collaborator acknowledges that Government funds received by Collaborator from an agency of the Department of Health and Human Services may not be used to fund ICD under this CRADA. If Collaborator has agreed to provide funds to ICD then the payment schedule appears in Appendix B and Collaborator will make payments according to that schedule.  If Collaborator fails to make any scheduled payment, ICD will not be obligated to perform any of the research and development activities specified herein or to take any other action required by this CRADA until the funds are received.  ICD will use these funds exclusively for the purposes of this CRADA. Each Party will maintain separate and distinct current accounts, records, and other evidence supporting its financial obligations under this CRADA and, upon written request, will provide the other Party a Fiscal Report according to Paragraph 4.3, which delineates all payments made and all obligated expenses, along with the Final Research Report described in Paragraph 4.2.

 

5.4          Capital Equipment.  Collaborator’s commitment, if any, to provide ICD with capital equipment to enable the research and development activities under the Research Plan appears in Appendix B. If Collaborator transfers to ICD the capital equipment or provides funds for ICD to purchase it, then ICD will own the equipment.  If Collaborator loans capital equipment to ICD for use during the CRADA, Collaborator will be responsible for paying all costs and fees associated with the transport, installation, maintenance, repair, removal, or disposal of the equipment, and ICD will not be liable for any damage to the equipment.

 

Article 6.               Intellectual Property

 

6.1          Ownership of CRADA Subject Inventions, CRADA Data, and CRADA Materials.  Subject to the Government license described in Paragraph 7.5, the sharing requirements of Paragraph 8.1 and the regulatory filing requirements of Paragraph 8.2, the producing Party will retain sole ownership of and title to all CRADA Subject Inventions, all copies of CRADA Data, and all CRADA Materials produced solely by its employee(s).  The Parties will own jointly all CRADA Subject Inventions invented jointly and all CRADA Materials developed jointly.  A PHS contractor’s or grantee’s rights in data it generates will not be affected by this CRADA.

 

6.2          Reporting.  The Parties will promptly report to each other in writing each CRADA Subject Invention reported by their respective personnel, and any Patent Applications filed thereon, resulting from the research and development activities conducted under this CRADA.

 

	
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Each Party will report all CRADA Subject Inventions to the other Party in sufficient detail to

 

determine inventorship, which will be determined in accordance with U.S. patent law.  These reports will be treated as Confidential Information in accordance with Article 8.  Formal reports will be made by and to the Patenting and Licensing Offices identified on the Contacts Information Page herein.

 

6.3          Filing of Patent Applications.  Each Party will make timely decisions regarding the filing of Patent Applications on the CRADA Subject Inventions made solely by its employee(s), and will notify the other Party in advance of filing.  Collaborator will have the first opportunity to file a Patent Application on joint CRADA Subject Inventions and will notify PHS of its decision within sixty (60) days of an Invention being reported or at least thirty (30) days before any patent filing deadline, whichever occurs sooner.  If Collaborator fails to notify PHS of its decision within that time period or notifies PHS of its decision not to file a Patent Application, then PHS has the right to file a Patent Application on the joint CRADA Subject Invention.  Neither Party will be obligated to file a Patent Application.  Collaborator will place the following statement in any Patent Application it files on a CRADA Subject Invention: “This invention was created in the performance of a Cooperative Research and Development Agreement with the [INSERT into Agency’s model as appropriate: National Institutes of Health, Food and Drug Administration, Centers for Disease Control and Prevention], an Agency of the Department of Health and Human Services.  The Government of the United States has certain rights in this invention.” If either Party files a Patent Application on a joint CRADA Subject Invention, then the filing Party will include a statement within the Patent Application that clearly identifies the Parties and states that the joint CRADA Subject Invention was made under this CRADA.

 

6.4          Patent Expenses.  Unless agreed otherwise, the Party filing a Patent Application will pay all preparation and filing expenses, prosecution fees, issuance fees, post issuance fees, patent maintenance fees, annuities, interference expenses, and attorneys’ fees for that Patent Application and any resulting Patent(s).  If a license to any CRADA Subject Invention is granted to Collaborator, then Collaborator will be responsible for all expenses and fees, past and future, in connection with the preparation, filing, prosecution, and maintenance of any Patent Applications and Patents claiming exclusively licensed CRADA Subject Inventions and will be responsible for a pro-rated share, divided equally among all licensees, of those expenses and fees for non-exclusively licensed CRADA Subject Inventions.  Collaborator may waive its exclusive option rights at any time, and incur no subsequent financial obligation for those Patent Application(s) or Patent(s).

 

6.5          Prosecution of Patent Applications.  The Party filing a Patent Application will provide the non-filing Party with a copy of any official communication relating to prosecution of the Patent Application within thirty (30) days of transmission of the communication.  Each Party will also provide the other Party with the power to inspect and make copies of all documents retained in the applicable Patent Application or Patent file.  The Parties agree to consult with

 

	
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each other regarding the prosecution of Patent Applications directed to joint CRADA Subject Inventions.  If Collaborator elects to file and prosecute Patent Applications on joint CRADA Subject Inventions, then Collaborator agrees to use the U.S.P.T.O. Customer Number Practice 

and/or grant PHS a power(s) of attorney (or equivalent) necessary to assure PHS access to its intellectual property rights in these Patent Applications.  PHS and Collaborator will cooperate with each other to obtain necessary signatures on Patent Applications, assignments, or other documents.

 

Article 7.               Licensing

 

7.1          Background Inventions.  Other than as specifically stated in this Article 7, nothing in this CRADA will be construed to grant any rights in one Party’s Background Invention(s) to the other Party, except to the extent necessary for the Parties to conduct the research and development activities described in the Research Plan.

 

7.2          Collaborator’s License Option to CRADA Subject Inventions.  With respect to Government rights to any CRADA Subject Invention made solely by an ICD employee(s) or made jointly by an ICD employee(s) and a Collaborator employee(s) for which a Patent Application was filed, PHS hereby grants to Collaborator an exclusive option to elect an exclusive or nonexclusive commercialization license.  The license will be substantially in the form of the appropriate model PHS license agreement and will fairly reflect the nature of the CRADA Subject Invention, the relative contributions of the Parties to the CRADA Subject Invention and the CRADA, a plan for the development and marketing of the CRADA Subject Invention, the risks incurred by Collaborator, and the costs of subsequent research and development needed to bring the CRADA Subject Invention to the marketplace.  The field of use of the license will not exceed the scope of the Research Plan.

 

7.3          Exercise of Collaborator’s License Option.  To exercise the option of Paragraph 7.2 Collaborator must submit a written notice to the PHS Patenting and Licensing Contact identified on the Contacts Information Page (and provide a copy to the ICD Contact for CRADA Notices) within three (3) months after either (i) Collaborator receives written notice from PHS that the Patent Application has been filed or (ii) the date on which Collaborator files the Patent Application.  The written notice exercising this option will include a completed “Application for License to Public Health Service Inventions” and will initiate a negotiation period that expires nine (9) months after the exercise of the option.  If PHS has not responded in writing to the last proposal by Collaborator within this nine (9) month period, the negotiation period will be extended to expire one (1) month after PHS so responds, during which month Collaborator may accept in writing the final license proposal of PHS. In the absence of Collaborator’s exercise of the option, or upon election of a nonexclusive license, PHS will be free to license the CRADA Subject Invention to others.  These time periods may be extended at the sole discretion of PHS upon good cause shown in writing by Collaborator.

 

7.4          Government License in ICD Sole CRADA Subject Inventions and Joint CRADA 

 

	
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Subject Inventions.  Pursuant to 15 U.S.C. § 3710a(b)(1)(A), for CRADA Subject Inventions owned solely by ICD or jointly by ICD and Collaborator, and licensed pursuant to the option of Paragraph 7.2, Collaborator grants to the Government a nonexclusive, nontransferable, irrevocable, paid-up license to practice the CRADA Subject Invention or have the CRADA 

Subject Invention practiced throughout the world by or on behalf of the Government.  In the exercise of this license, the Government will not publicly disclose trade secrets or commercial or financial information that is privileged or confidential within the meaning of 5 U.S.C. § 552(b)(4) or which would be considered privileged or confidential if it had been obtained from a non-federal party.

 

7.5          Government License in Collaborator Sole CRADA Subject Inventions.  Pursuant to 15 U.S.C. § 3710a(b)(2), for CRADA Subject Inventions made solely by an employee of Collaborator, Collaborator grants to the Government a nonexclusive, nontransferable, irrevocable, paid-up license to practice the CRADA Subject Invention or have the CRADA Subject Invention practiced throughout the world by or on behalf of the Government for research or other Government purposes.

 

7.6          Third Party License.  Pursuant to 15 U.S.C. § 3710a(b)(1)(B), if PHS grants Collaborator an exclusive license to a CRADA Subject Invention made solely by an ICD employee or jointly with a Collaborator employee, the Government will retain the right to require Collaborator to grant to a responsible applicant a nonexclusive, partially exclusive, or exclusive sublicense to use the CRADA Subject Invention in Collaborator’s licensed field of use on terms that are reasonable under the circumstances; or, if Collaborator fails to grant a license, to grant a license itself.  The exercise of these rights by the Government will only be in exceptional circumstances and only if the Government determines (i) the action is necessary to meet health or safety needs that are not reasonably satisfied by Collaborator, (ii) the action is necessary to meet requirements for public use specified by federal regulations, and such requirements are not reasonably satisfied by Collaborator; or (iii) Collaborator has failed to comply with an agreement containing provisions described in 15 U.S.C. § 3710a(c)(4)(B).  The determination made by the Government under this Paragraph is subject to administrative appeal and judicial review under 35 U.S.C. § 203(2).

 

7.7          Third-Party Rights In ICD Sole CRADA Subject Inventions.  For a CRADA Subject Invention conceived prior to the Effective Date solely by an ICD employee that is first actually reduced to practice after the Effective Date in the performance of the Research Plan, the option offered to Collaborator in Paragraph 7.2 may be restricted if, prior to the Effective Date, PHS had filed a Patent Application and has either offered or granted a license in the CRADA Subject Invention to a third party.  Collaborator nonetheless retains the right to apply for a license to any such CRADA Subject Invention in accordance with the terms and procedures of 35 U.S.C. § 209 and 37 C.F.R. Part 404.

 

7.8          Joint CRADA Subject Inventions Not Exclusively Licensed by Collaborator.  If 

 

	
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Collaborator does not acquire an exclusive commercialization license in a joint CRADA Subject Invention in all fields of use then, for those fields of use not exclusively licensed to Collaborator, each Party will have the right to use the joint CRADA Subject Invention and to license its use to others, and each Party will cooperate with the other, as necessary, to fulfill international licensing requirements.  The Parties may agree to a joint licensing approach for any remaining fields of use.

 

Article 8.               Rights of Access and Publication

 

8.1          Right of Access to CRADA Data and CRADA Materials.  ICD and Collaborator agree to exchange all CRADA Data and to share all CRADA Materials.  If the CRADA is terminated, both Parties agree to provide CRADA Materials in quantities needed to complete the Research Plan.  Such provision will occur before the termination date of the CRADA or sooner, if required by the Research Plan.  If Collaborator possesses any human biological specimens from clinical trials under the CRADA, the specimens must be handled as described in the Protocol or as otherwise directed by ICD before the termination date of the CRADA.

 

8.2          Use of CRADA Data and CRADA Materials.  The Parties will be free to utilize CRADA Data and CRADA Materials internally for their own purposes, consistent with their obligations under this CRADA. ICD may share CRADA Data or CRADA Materials with any contractors, grantees, or agents it has engaged to conduct the CRADA research and development activities, provided the obligations of this Article 8.2 are simultaneously conveyed.  Collaborator may share CRADA Data or CRADA Materials with any contractors, Affiliates, or agents it has engaged to conduct the CRADA research and development activities, provided the obligations of this Article 8.2 are simultaneously conveyed.

 

8.2.1       CRADA Data.

 

Collaborator and ICD will use reasonable efforts to keep CRADA Data confidential until published or until corresponding Patent Applications are filed.  To the extent permitted by law, each Party will have the right to use any and all CRADA Data in and for any regulatory filing by or on behalf of the Party.

 

8.2.2       CRADA Materials.

 

Collaborator and ICD will use reasonable efforts to keep descriptions of CRADA Materials confidential until published or until corresponding Patent Applications are filed.  Collaborator acknowledges that the basic research mission of PHS includes sharing with third parties for further research those research resources made in whole or in part with NIH funding.  Consistent with this mission and the tenets articulated in “Sharing of Biomedical Research Resources: Principles and Guidelines for Recipients of NIH Research Grants and Contracts,” December 1999, available at http://ott.od.nih.gov/NewPages/RTguide_final.html, following publication either Party may make available to third parties for further research those CRADA Materials made jointly by both PHS and Collaborator.  

 

	
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Notwithstanding the above, if those joint CRADA Materials are the subject of a pending Patent Application or a Patent, or were created using a patent-pending or patented material or technology, the Parties may agree to restrict distribution or freely distribute them.  Either Party may distribute those CRADA Materials made solely by the other Party only upon written consent from that other Party or that other Party’s designee.

 

8.3          Confidential Information.  Each Party agrees to limit its disclosure of Confidential Information to the amount necessary to carry out the Research Plan, and will place a confidentiality notice on all this information.  A Party orally disclosing Confidential Information to the other Party will summarize the disclosure in writing and provide it to the other Party within fifteen (15) days of the disclosure.  Each Party receiving Confidential Information agrees to use it only for the purposes described in the Research Plan.  Either Party may object to the designation of information as Confidential Information by the other Party.

 

8.4          Protection of Confidential Information.  Confidential Information will not be disclosed, copied, reproduced or otherwise made available to any other person or entity without the consent of the owning or providing Party except as required by a court or administrative body of competent jurisdiction, or federal law or regulation.  Each Party agrees to use reasonable efforts to maintain the confidentiality of Confidential Information, which will in no instance be less effort than the Party uses to protect its own Confidential Information.  Each Party agrees that a Party receiving Confidential Information will not be liable for the disclosure of that portion of the Confidential Information which, after notice to and consultation with the disclosing Party, the receiving Party determines may not be lawfully withheld, provided the disclosing Party has been given a reasonable opportunity to seek a court order to enjoin disclosure.

 

8.5          Human Subject Protection.  The research to be conducted under this CRADA involves Human Subjects or human tissues within the meaning of 45 C.F.R. Part 46, and all research to be performed under this CRADA will conform to applicable federal laws and regulations.  Additional information is available from the HHS Office for Human Research Protections (http://www.hhs.gov/ohrp/).

 

8.6          Duration of Confidentiality Obligation.  The obligation to maintain the confidentiality of Confidential Information will expire at the earlier of the date when the information is no longer Confidential Information as defined in Paragraph 2.4 or three (3) years after the expiration or termination date of this CRADA, except for IPI, for which the obligation to maintain confidentiality will extend indefinitely.  Collaborator may request an extension to this term when necessary to protect Confidential Information relating to products not yet commercialized.

 

8.7          Publication.  The Parties are encouraged to make publicly available the results of their research and development activities.  Before either Party submits a paper or abstract for publication or otherwise intends to publicly disclose information about a CRADA Subject Invention, CRADA Data, or CRADA Materials, the other Party will have thirty (30) days to review proposed manuscripts and three (3) days to review proposed abstracts to assure that

 

	
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Confidential Information is protected.  Either Party may request in writing that the proposed publication or other disclosure be delayed for up to thirty (30) additional days as necessary to file a Patent Application.

 

8.8          Clinical Investigators’ Research and Development Activities.  Although this CRADA does not grant to Collaborator any rights to Inventions made or Raw Data generated by ICD’s contractors or grantees, as they are not parties to this CRADA, ICD agrees that:

 

8.8.1       Subject to the other provisions of Article 8 of this CRADA, ICD will maintain, to the extent permitted by law, all Clinical Data in ICD’s Possession and Control as Confidential Information, and make them available to Collaborator for its own use and for exclusive use in obtaining regulatory approval for the commercial marketing of Test Article and related CRADA Subject Inventions.

 

8.8.2       With regard to Collaborator’s Confidential Information, ICD will require the Clinical Investigators to agree to confidentiality provisions at least as restrictive as those provided in this CRADA and to Collaborator’s use of data in accordance with Paragraph 8.8.1 for obtaining regulatory approval for marketing Test Article.

 

8.8.3       If Collaborator wants access to Raw Data or any other data in the possession of the Clinical Investigators working with Test Article, Collaborator must first contact the CRADA PI. Collaborator will bear any costs associated with Raw Data provided in formats customized for Collaborator.

 

8.8.4       Collaborator’s right to access Clinical Data in ICD’s Possession and Control under Paragraph 8.8 is dependent upon Collaborator’s continued development and commercialization of Investigational Agent.  If Collaborator fails to continue development or commercialization of Investigational Agent without the transfer of its development efforts to another party within ninety (90) days of discontinuation, ICD has the right to make Clinical Data in ICD’s Possession and Control available to a third party.

 

Article 9.               Representations and Warranties

 

9.1          Representations of ICD.  ICD hereby represents to Collaborator that:

 

9.1.1       ICD has the requisite power and authority to enter into this CRADA and to perform according to its terms, and that ICD’s official signing this CRADA has authority to do so.

 

9.1.2       To the best of its knowledge and belief, neither ICD nor any of its personnel involved in this CRADA is presently subject to debarment or suspension by any agency of the Government which would directly affect its performance of the CRADA. Should ICD or any of its personnel involved in this CRADA be debarred or suspended during the term of this CRADA, ICD will notify Collaborator within thirty (30) days of receipt of final notice.

 

	
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9.2          Representations and Warranties of Collaborator.  Collaborator hereby represents and warrants to ICD that:

 

9.2.1       Collaborator has the requisite power and authority to enter into this CRADA and to perform according to its terms, and that Collaborator’s official signing this CRADA has authority to do so.

 

9.2.2       Neither Collaborator nor any of its personnel involved in this CRADA, including Affiliates, agents, and contractors are presently subject to debarment or suspension by any agency of the Government.  Should Collaborator or any of its personnel involved in this CRADA be debarred or suspended during the term of this CRADA, Collaborator will notify ICD within thirty (30) days of receipt of final notice.

 

9.2.3       Subject to Paragraph 12.3, and if and to the extent Collaborator has agreed to provide funding under Appendix B, Collaborator is financially able to satisfy these obligations in a timely manner.

 

9.2.4       The Test Article provided has been produced in accordance with the FDA’s current Good Manufacturing Practice set out in 21 C.F.R. §§ 210-211, and ICH QA7, and meets the specifications cited in the Certificate of Analysis and Investigator’s Brochure provided.

 

Article 10.            Expiration and Termination

 

10.1        Expiration.  This CRADA will expire on the last date of the term set forth on the Summary Page.  In no case will the term of this CRADA extend beyond the term indicated on the Summary Page unless it is extended in writing in accordance with Paragraph 13.6.

 

10.2        Termination by Mutual Consent.  ICD and Collaborator may terminate this CRADA at any time by mutual written consent.

 

10.3        Unilateral Termination.  Either ICD or Collaborator may unilaterally terminate this CRADA at any time by providing written notice at least sixty (60) days before the desired termination date.  ICD may, at its option, retain funds transferred to ICD before unilateral termination by Collaborator for use in completing the Research Plan.  If Collaborator terminates this Agreement before the completion of all approved or active Protocol(s), then Collaborator will supply enough Test Article (and Placebo, if applicable) to complete these Protocol(s) unless termination is for safety concerns.

 

10.4        Funding for ICD Personnel.  If Collaborator has agreed to provide funding for ICD personnel and this CRADA is mutually or unilaterally terminated by Collaborator before its expiration, then Collaborator agrees that funds for that purpose will be available to ICD for a

 

	
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period of six (6) months after the termination date or until the expiration date of the CRADA, whichever occurs sooner.  If there are insufficient funds to cover this expense, Collaborator agrees to pay the difference.

 

10.5        New Commitments.  Neither Party will incur new expenses related to this CRADA after expiration, mutual termination, or a notice of a unilateral termination and will, to the extent feasible, cancel all outstanding commitments and contracts by the termination date.  Collaborator acknowledges that ICD will have the authority to retain and expend any funds for up to one (1) year subsequent to the expiration or termination date to cover any unpaid costs obligated during the term of the CRADA in undertaking the research and development activities set forth in the Research Plan.

 

10.6        Collaborator Failure to Continue Development.  If Collaborator suspends development of the Test Article without the transfer of its active development efforts, assets, and obligations to a third party within ninety (90) days of discontinuation, Collaborator agrees that ICD may continue developing the Test Article.  In that event, the following will apply:

 

10.6.1     Collaborator agrees to transfer to ICD all information necessary to enable ICD to contract for the manufacture of the Test Article and, unless abandoned for reasons relating to safety as determined by the data safety monitoring board, to provide the Test Article (and Placebo, if any) in Collaborator’s inventory to ICD.

 

10.6.2     Further, Collaborator hereby grants to ICD a nonexclusive, irrevocable, world-wide, paid-up license to practice, or have practiced for or on behalf of the Government, any Background Invention that Collaborator may currently have or will obtain on the Test Article, its manufacture, or on any method of using the Test Article for the indication(s) described in the Research Plan, including the right to sublicense to third parties.

 

Article 11.            Disputes

 

11.1        Settlement.  Any dispute arising under this CRADA which is not disposed of by agreement of the CRADA Principal Investigators will be submitted jointly to the signatories of this CRADA. If the signatories, or their designees, are unable to jointly resolve the dispute within thirty (30) days after notification thereof, the Assistant Secretary for Health (or his/her designee or successor) will propose a resolution.  Nothing in this Paragraph will prevent any Party from pursuing any additional administrative remedies that may be available and, after exhaustion of such administrative remedies, pursuing all available judicial remedies.

 

11.2        Continuation of Work.  Pending the resolution of any dispute or claim pursuant to this Article 11, the Parties agree that performance of all obligations will be pursued diligently.

 

	
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Article 12.            Liability

 

12.1        NO WARRANTIES. EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER, INCLUDING THE CONDITIONS OF THE RESEARCH OR ANY INVENTION OR MATERIAL, WHETHER TANGIBLE OR INTANGIBLE, MADE OR DEVELOPED UNDER OR OUTSIDE THE SCOPE OF THIS CRADA, OR THE OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF THE RESEARCH OR ANY INVENTION OR MATERIAL, OR THAT A TECHNOLOGY UTILIZED BY A PARTY IN THE PERFORMANCE OF THE RESEARCH PLAN DOES NOT INFRINGE ANY THIRD-PARTY PATENT RIGHTS.

 

12.2        Indemnification and Liability.  Collaborator agrees to hold the Government harmless and to indemnify the Government for all liabilities, demands, damages, expenses and losses arising out of the use by Collaborator for any purpose of the CRADA Data, CRADA Materials or CRADA Subject Inventions produced in whole or part by ICD employees under this CRADA, unless due to the negligence or willful misconduct of ICD, its employees, or agents.  The Government has no statutory authority to indemnify Collaborator.  Each Party otherwise will be liable for any claims or damages it incurs in connection with this CRADA, except that ICD, as an agency of the Government, assumes liability only to the extent provided under the Federal Tort Claims Act , 28 U.S.C. Chapter 171.

 

12.3        Force Majeure.  Neither Party will be liable for any unforeseeable event beyond its reasonable control and not caused by its own fault or negligence, which causes the Party to be unable to perform its obligations under this CRADA, and which it has been unable to overcome by the exercise of due diligence.  If a force majeure event occurs, the Party unable to perform will promptly notify the other Party.  It will use its best efforts to resume performance as quickly as possible and will suspend performance only for such period of time as is necessary as a result of the force majeure event.

 

Article 13.            Miscellaneous

 

13.1        Governing Law.  The construction, validity, performance and effect of this CRADA will be governed by U.S. federal law, as applied by the federal courts in the District of Columbia.  If any provision in this CRADA conflicts with or is inconsistent with any U.S. federal law or regulation, then the U.S. federal law or regulation will preempt that provision.

 

13.2        Compliance with Law.  ICD and Collaborator agree that they will comply with, and advise any contractors, grantees, or agents they have engaged to conduct the CRADA research and development activities to comply with, all applicable Executive Orders, statutes, and HHS regulations relating to research on human subjects (45 C.F.R. Part 46, 21 C.F.R. Parts 50 and 56) and relating to the appropriate care and use of laboratory animals (7 U.S.C. §§ 2131 et seq.; 9 C.F.R. Part 1, Subchapter A).  ICD and Collaborator will advise any contractors, grantees, or agents they have engaged to conduct clinical trials for this CRADA that they must comply with all applicable federal regulations for the protection of Human Subjects, which may include the Standards for Privacy of Individually Identifiable Health Information set forth in 45 C.F.R. Part

 

	
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164.  Collaborator agrees to ensure that its employees, contractors, and agents who might have access to a “select agent or toxin” (as that term is defined in 42 C.F.R. §§ 73.4-73.5) transferred from ICD is properly licensed to receive the “select agent or toxin.”

 

13.3        Waivers.  None of the provisions of this CRADA will be considered waived by any Party unless a waiver is given in writing to the other Party.  The failure of a Party to insist upon strict performance of any of the terms and conditions hereof, or failure or delay to exercise any rights provided herein or by law, will not be deemed a waiver of any rights of any Party.

 

13.4        Headings.  Titles and headings of the articles and paragraphs of this CRADA are for convenient reference only, do not form a part of this CRADA, and will in no way affect its interpretation.

 

13.5        Severability.  The illegality or invalidity of any provisions of this CRADA will not impair, affect, or invalidate the other provisions of this CRADA.

 

13.6        Amendments.  Minor modifications to the Research Plan may be made by the mutual written consent of the CRADA Principal Investigators.  Substantial changes to the CRADA, extensions of the term, or any changes to Appendix C will become effective only upon a written amendment signed by the signatories to this CRADA or by their representatives duly authorized to execute an amendment.  A change will be considered substantial if it directly expands the range of the potential CRADA Subject Inventions, alters the scope or field of any license option governed by Article 7, or requires a significant increase in the contribution of resources by either Party.

 

13.7        Assignment.  Neither this CRADA nor any rights or obligations of any Party hereunder will be assigned or otherwise transferred by either Party without the prior written consent of the other Party.  This CRADA will be binding upon and inure to the benefit of the Parties and their respective successors and permitted assigns.

 

13.8        Notices.  All notices pertaining to or required by this CRADA will be in writing, signed by an authorized representative of the notifying Party, and delivered by first class, registered, or certified mail, or by an express/overnight commercial delivery service, prepaid and properly addressed to the other Party at the address designated on the Contacts Information Page, or to any other address designated in writing by the other Party.  Notices will be considered timely if received on or before the established deadline date or sent on or before the deadline date as verifiable by U.S. Postal Service postmark or dated receipt from a commercial carrier.  Notices regarding the exercise of license options will be made pursuant to Paragraph 7.3.  Either Party may change its address by notice given to the other Party in the manner set forth above.

 

13.9        Independent Contractors.  The relationship of the Parties to this CRADA is that of independent contractors and not agents of each other or joint venturers or partners.  Each Party will maintain sole and exclusive control over its personnel and operations.

 

	
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13.10      Use of Name; Press Releases.  By entering into this CRADA, the Government does not directly or indirectly endorse any product or service that is or will be provided, whether directly or indirectly related to either this CRADA or to any patent or other intellectual-property license or agreement that implements this CRADA by Collaborator, its successors, assignees, or licensees.  Collaborator will not in any way state or imply that the Government or any of its organizational units or employees endorses any product or services.  Each Party agrees to provide proposed press releases that reference or rely upon the work under this CRADA to the other Party for review and comment at least five (5) business days before publication.  Either Party may disclose the Title and Abstract of the CRADA to the public without the approval of the other Party.

 

13.11      Reasonable Consent.  Whenever a Party’s consent or permission is required under this CRADA, its consent or permission will not be unreasonably withheld.

 

13.12      Export Controls.  Collaborator agrees to comply with U.S. export law and regulations.  If Collaborator has a need to transfer any CRADA Materials made in whole or in part by ICD, or ICD Materials, or ICD’s Confidential Information to a person located in a country other than the United States, to an Affiliate organized under the laws of a country other than the United States, or to an employee of Collaborator in the United States who is not a citizen or permanent resident of the United States, Collaborator will acquire any and all necessary export licenses and other appropriate authorizations.

 

13.13      Entire Agreement.  This CRADA constitutes the entire agreement between the Parties concerning the subject matter of this CRADA and supersedes any prior understanding or written or oral agreement.

 

13.14      Survivability.  The provisions of Paragraphs 3.3, 3.4, 3.8, 4.2, 4.3, 5.3, 5.4, 6.1-9.2, 10.3-10.6, 11.1, 11.2, 12.1-12.3, 13.1-13.3, 13.7, 13.10 and 13.14 will survive the expiration or early termination of this CRADA.

 

SIGNATURES BEGIN ON THE NEXT PAGE

 

 

	
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SIGNATURE PAGE

 

ACCEPTED AND AGREED

 

BY EXECUTING THIS AGREEMENT, EACH PARTY REPRESENTS THAT ALL STATEMENTS MADE HEREIN ARE TRUE, COMPLETE, AND ACCURATE TO THE BEST OF ITS KNOWLEDGE. COLLABORATOR ACKNOWLEDGES THAT IT MAY BE SUBJECT TO CRIMINAL, CIVIL, OR ADMINISTRATIVE PENALTIES FOR KNOWINGLY MAKING A FALSE, FICTITIOUS, OR FRAUDULENT STATEMENT OR CLAIM.

 

	
FOR ICD:
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
[***]
    	
 
    	
08/01/08
    
	
[***]
    	
 
    	
Date
    
	
Deputy Director, NCI
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
FOR COLLABORATOR:
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
[***]
    	
 
    	
08/12/08
    
	
[***]
    	
 
    	
Date
    
	
Title: President and   Chief Executive Officer
    	
 
    	
 
    

 

	
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CONTACTS INFORMATION PAGE

 

	
CRADA Notices
    
	
 
    	
 
    
	
For ICD:
    	
For Collaborator:
    
	
 
    	
 
    
	
Technology Transfer   Center
    	
[***]
    
	
National Cancer   Institute
    	
President and CEO
    
	
6120 Executive Blvd.,   Suite 450
    	
BN ImmunoTherapeutics, Inc.
    
	
Rockville, MD   20852-7181
    	
2425 Garcia Avenue
    
	
Phone: 301-496-0477
    	
Mountain View, CA 94043
    
	
Fax: 301-402-2117
    	
Tel: [***]
    
	
 
    	
Fax: [***]
    
	
 
    
	
Patenting and Licensing
    
	
 
    	
 
    
	
For ICD:
    	
For Collaborator (if   separate from above):
    
	
 
    	
 
    
	
Division Director,   Division of Technology
    	
[***]
    
	
Development and   Transfer
    	
President and CEO
    
	
NIH Office of   Technology Transfer
    	
BN   ImmunoTherapeutics, Inc.
    
	
6011 Executive   Boulevard, Suite 3252425
    	
Garcia Avenue
    
	
Rockville, Maryland   20852-3804
    	
Mountain View, CA 94043
    
	
Tel: 301-496-7057
    	
Tel: [***]
    
	
Fax: 301-402-0220
    	
Fax: [***]
    
	
 
    
	
Delivery of Materials Identified In Appendix B (if   any)
    
	
 
    	
 
    
	
For ICD:
    	
For Collaborator:
    
	
 
    	
 
    
	
Dr. [***]
    	
[***]
    
	
10 Center Drive, MSC   1750
    	
Senior Director,   Clinical Operations
    
	
Building 10, Room 8B09
    	
BN   ImmunoTherapeutics, Inc.
    
	
Bethesda, MD 20892
    	
2425 Garcia Avenue
    
	
Phone: [***]
    	
Mountain View, CA 94043
    
	
Fax: [***]
    	
Tel: [***]
    
	
Email: [***]
    	
Fax: [***]
    
	
 
    	
Email: [***]
    

 

	
ICD Project Officer for Extramural Investigators
    
	
 
    	
 
    
	
Name:
    	
[***],   Ph.D.
    
	
Branch:
    	
NCI, DCTD, CTEP
    
	
Address:
    	
6130 Executive Blvd.,   Suite 7108, Rockville, MD 20852, Phone: [***]
    

 

	
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SUMMARY PAGE

 

EITHER PARTY MAY, WITHOUT FURTHER CONSULTATION OR PERMISSION,

RELEASE THIS SUMMARY PAGE TO THE PUBLIC.

 

	
TITLE OF CRADA: The Development of Recombinant Poxviruses   as Vaccine Immunotherapies for the Treatment and/or Prevention of Human   Prostate Cancer
    
	
 
    	
 
    
	
PHS [ICD] Component:
    	
National Cancer   Institute
    
	
ICD CRADA Principal   Investigator:
    	
Jeffrey Schlom, Ph.D.
    
	
 
    	
 
    
	
Collaborator:
    	
BN ImmunoTherapeutics
    
	
Collaborator CRADA   Principal Investigator:
    	
Reiner Laus, M.D.
    
	
Term of CRADA:
    	
five (5) years   from the Effective Date
    

 

ABSTRACT OF THE RESEARCH PLAN:

 

BN ImmunoTherapeutics, Inc. and the National Cancer Institute, National Institutes of Health, will collaborate under a Cooperative Research and Development Agreement on the preclinical and clinical development of recombinant poxviruses expressing tumor-associated antigens as potential vaccines for the prevention and/or treatment of human prostate cancer.

 

	
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PUBLIC HEALTH SERVICE

COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

FOR EXTRAMURAL-PHS CLINICAL RESEARCH

 

APPENDIX A

 

RESEARCH PLAN

 

TITLE OF CRADA

The Development of Recombinant Poxviruses As Vaccine Immunotherapies for the 
 Treatment and/or Prevention of Human Prostate Cancer

 

NCI, NIH Principal Investigator

Jeffrey Schlom, Ph.D.

Laboratory of Tumor Immunology and Biology (LTIB), Center for Cancer Research
 (CCR), National Cancer Institute (NCI)

 

Collaborator Principal Investigator

Reiner Laus, M.D.

BN ImmunoTherapeutics, Inc. (BNIT)

 

Term of CRADA

Five (5) years from the Effective Date.

 

GOAL OF THIS CRADA

 

The principal goal of this CRADA is to develop recombinant poxviruses as vaccines that can be used for the therapy and/or prevention of human prostate cancer.The scope of this CRADA including any in vitro and in vivo testing conducted by Dr. Jeffrey Schlom’s laboratory is strictly limited to the development of recombinant poxviruses encoding for prostate-associated antigens, cytokines, and/or immunostimulatory molecules as vaccine immunotherapies for the treatment and prevention of prostate cancer.

 

[***]

 

[***]

 

[***]

 

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[***]

 

[***]                      [***]

 

[***]

 

GLOSSARY of TERMS

 

Vaccinia: Vaccinia is the poxvirus that has been used in the smallpox eradication program. It is not the smallpox virus, but a virus originally derived from cowpox. Many genes can be inserted into vaccinia and other poxviruses. When this occurs, it is then termed a recombinant virus (e.g., rV- for recombinant vaccinia). Vaccinia is a replication competent virus and has been used as the primary (first) vaccination in diversified prime and boost vaccine regimens in both pre-clinical and clinical studies.

 

Fowlpox: Fowlpox is replication incompetent in mammalian cells. Many genes can be

 

A-2

 

inserted into fowlpox. When this occurs, it is then termed a recombinant fowlpox (rF-). Recombinant fowlpox has been used as multiple booster vaccinations in diversified prime and boost vaccine regimens. Fowlpox appears to be very safe and is a member of the Avipox family.

 

MVA: MVA stands for modified vaccinia Ankara.

 

TRICOM: TRICOM is a triad of T-cell costimulatory molecules consisting of the following human T-cell costimulatory molecule genes: B7.1, ICAM-l and LFA-3. TRICOM was developed at NCI in the LTIB. TRICOM has been shown to activate T cells more than the additive effect of each costimulatory molecule when used individually.   A T-cell costimulatory molecule is necessary for the enhanced activation of human T cells, which are believed to be the primary cell type responsible for vaccine-mediated anti-tumor activity. The NCI has demonstrated that the addition of all three of these genes, i.e., TRICOM, into recombinant vaccinia and fowlpox results in enhanced activation of T cells. This has been shown in both murine and human systems in vitro and in murine systems in vivo. It also appears to be the case in clinical trials.

 

PSA: PSA (prostate-specific antigen) is a tumor-associated antigen expressed in prostate cancer and normal prostate tissue. PSA is also expressed in some other carcinomas. The LTIB has developed a PSA agonist construct, which is a modified form of the PSA gene to make it more immunogenic. The PROSTVAC construct contains the entire PSA gene with the PSA agonist epitope.

 

PROSTVAC (also called Investigational Agent): PROSTVAC consists of rV-PSA/TRICOM and rF-PSA/TRICOM, which are used in a prime and boost vaccine strategy. The PSA gene contains the agonist epitope.

 

rF-GM-CSF: rF-GM-CSF is a recombinant fowlpox expressing the human GM-CSF (granulocyte macrophage colony stimulating factor) gene. It has been demonstrated in preclinical studies to enhance the recruitment of dendritic cells to regional nodes of the vaccine site.

 

INTRODUCTION

 

Dr. Jeffrey Schlom and his colleagues at the LTIB, NCI have developed a number of replication competent and replication defective poxvirus-based vectors containing transgenes for tumor-associated antigens (TAAs) as vaccine immunotherapies for the treatment and prevention of human cancers, including prostate cancer.  They have also developed a number of preclinical models and vaccine strategies to investigate the therapeutic benefits of these vaccines against cancer.  In these approaches, TAAs which are primarily expressed in human tumor cells and not expressed or minimally expressed in normal tissues have been employed to generate a tumor-associated immune response that results in tumor destruction.

 

A-3

 

The LTIB has extensive experience in preclinical models in the analysis of immune responses directed against a range of TAAs. They have the demonstrated ability to analyze a range of immune cell subsets, including CD4, CD8, Natural Killer (NK), and regulatory T cells.  The LTIB also has extensive experience in the following:

(A) The development and use of animal models to analyze both the immune response and the therapeutic efficacy of cancer vaccines.  They have developed animal models in which the tumors express self antigens so that one can assess the ability of a vaccine to break immune tolerance.  They have also developed animal models involving subcutaneous tumors, lung metastasis, orthotopic renal cell cancers, and spontaneous mammary carcinomas.

(B) The design and evaluation of vaccine combination therapy regimens, including the use of vaccines with chemotherapeutic agents, small molecule targeted therapeutics, monoclonal antibodies, external beam radiation, chelated radionuclides, and cytokines.

(C) The modification of human TAAs to enhance their immunogenicity and in the development of subsequent agonist epitopes of those TAAs.

(D) The analysis of human TAAs for their ability to activate human T-cell responses in vitro.

(E) The planning and carrying out of clinical trials involving cancer vaccines as monotherapy or in combination therapies for a range of human cancers.

(F) The analysis of immune responses of patients both prior to and post-vaccination.

 

BN ImmunoTherapeutics, Inc. (BNIT) has extensive experience in developing poxviral vaccines for cancer immunotherapy.  Their core technology is a proprietary recombinant poxvirus-based platform, Modified Vaccinia Ankara BN (MVA-BN®), which they are developing as an immunotherapy for breast, prostate, and other cancers.  BNIT is a subsidiary of Bavarian Nordic (BN).  BN has a dedicated research and development facility in Martinsried, Germany, where recombinant poxviruses are generated and produced for research use. Small scale manufacturing of research grade lots is provided by the facility at Martinsried. Initial 1000 dose lots have been completed for dozens of viral constructs to date. The site has produced multiple recombinant poxviruses encoding infectious disease antigens, and in conjunction with BNIT, multiple tumor antigen-expressing viruses. HIV nef, HIV polytope, and HIV multiantigen, Dengue, Japanese encephalitis, measles, and RSV viral vaccines have been constructed and manufactured. In conjunction with BNIT, Her2 and PAP/PSA double antigen expressing recombinant viruses have been developed. BNIT has also begun to construct additional vectors with immunomodulatory inserts.

 

BN also has a clinical scale cGMP facility in Berlin that produces vaccine for clinical trials. The facility has been in operation since 2002, and has produced over 14 lots of clinical trial grade material. The facility produces clinical trial lots at intermediate scale (100s to 1000s of doses) with cGMP compliant processes that are similar and scalable to commercial scale. Current commercial scale manufacturing is operational at the Kvistgaard, Denmark facility. The facility has the capability of producing 30 million doses/year.

 

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BACKGROUND

 

Historical Background

 

Under a now terminated CRADA [***] there was significant progress in the development of new recombinant poxviral vectors, preclinical evaluation of those vectors in murine in vitro and in vivo models, and in human in vitro models. These preclinical studies led to several Phase 1 and Phase 2 clinical studies, several of which showed evidence of clinical benefit in patients with a range of human carcinomas. Much progress was also made in (a) the identification and evaluation of prostate-associated antigens including human prostate-specific antigen (PSA) and the development of agonist epitopes to those antigens, which would render them more immunogenic, and (b) the identification of which T cell costimulatory molecules and combinations of those molecules best enhanced T cell responses. As a consequence of these studies, it was shown that the insertion of transgenes for a triad of the T cell costimulatory molecules B7.1, ICAM-1 and LFA-3 (designated TRICOM) into poxvirus vectors gave optimal effects; this was shown in preclinical studies to enhance immune responses and anti-tumor activity. As a consequence of these preclinical studies, clinical trials were initiated to evaluate the efficacy of vectors containing the transgene for a tumor-associated antigen, i.e., PSA, and the transgenes for either one, two or three T cell costimulatory molecules.

 

The enormous progress in both preclinical and clinical studies using the poxvirus vaccine technology is demonstrated in the 47 publications of preclinical studies in peer-review journals and the 12 clinical studies in peer-review journals that resulted from these collaborative activities (see References).

 

An overview of some of the published clinical results employing the recombinant poxvirus vaccines in patients with prostate cancer is as follows:

 

In a Phase 1 study in prostate cancer patients, rV-PSA was administered to 33 patients with biochemical progression after local therapy or with metastatic disease. PSA levels in 13/33 men became stable for at least 6 months post-vaccination. Nine patients remained stable for 11—25 months and six remained progression free with stable PSA. At the time of the publication, several patients remained without evidence of clinical progression for up to 21 months.

 

An NCI-sponsored ECOG randomized Phase 2 trial was then carried out using two different PSA pox vectors in different prime/boost regimens: rV-PSA(V) and/or rF-PSA(F) in patients (n = 64) with biochemical progression after local therapy for prostate cancer. At the 2-year follow-up, median time to PSA and/or clinical progression was 9.2 months in the FFFF cohort, 9.0 months in the FFFV cohort, and 18 months in the VFFF cohort.

 

The NCI then completed studies with a diversified prime-boost strategy involving priming with rV-PSA + rV-B7.1 followed by rF-PSA booster vaccinations.  In the first trial, 28

 

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patients with metastatic androgen independent prostate cancer (AIPC) were randomized to receive vaccine alone or vaccine plus weekly docetaxel. Patients on the vaccine arm alone were allowed to cross over to receive docetaxel at time of progression. After vaccine, median progression-free survival on docetaxel was 6.1 months compared with a progression-free survival of 3.7 months with the same docetaxel regimen and patient population at the same institution.

 

In another Phase 2 trial at the NCI, 42 patients with nonmetastatic AIPC and rising serum PSA were randomized to receive either vaccine (rV-PSA/B7.1 prime and rF-PSA boosts) or nilutamide, an androgen-receptor antagonist (ARA). After 6 months, patients with a rising PSA were allowed to “cross over” and receive a combination of both therapies. Median time to treatment failure was similar in the vaccine (9.9 months) and ARA (7.6 months) arms. However, for the patients who first received vaccine and then went on to receive vaccine plus ARA, time to treatment failure was 13.9 months from the time of initiation of ARA, and the time to treatment failure from the initiation of any therapy was 25.9 months. Of the initial randomized population (n = 21/cohort), for those patients who received nilutamide first (nilutamide alone or nilutamide then vaccine), 5-year overall survival was 38%, vs. a median overall survival of 59% for those patients who received vaccine first (vaccine alone or nilutamide plus vaccine).

 

The NCI then developed rV- and rF- vectors containing the transgenes for PSA and three human costimulatory molecules (B7.1, ICAM-1 and LFA-3, designated TRICOM). PSA-TRICOM was well tolerated in a Phase 1 study. Recent Phase 2 trials in patients with metastatic and locally advanced prostate cancer have shown clinical responses and drops in serum PSA. A sponsored multi-center randomized Phase 2 study in 125 patients with metastatic androgen-independent asymptomatic prostate cancer did not meet its primary endpoint of progression-free survival. However, patients’ overall survival data are currently being accumulated, with provocative results. Median overall survival thus far is 16.3 months for the control cohort (wild-type vector) (n = 41) vs. 24.4 months for those patients receiving PSA-TRICOM vaccines (n = 84). A recently completed NCI Phase 2 trial with PSA-TRICOM vaccines in prostate cancer patients with metastatic disease also demonstrated clinical responses and evidence of increased survival.

 

So therefore, the promising clinical results from these studies encourages the establishment of a new CRADA to allow for the continual development and manufacture of PROSTVAC and other poxvirus-based prostate cancer vaccines.

 

WORK SCOPE

 

Contributions of NCI and BNIT

 

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with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

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Contributions of NCI

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

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DESCRIPTION OF THE CONTRIBUTIONS AND RESPONSIBILITIES OF THE PARTIES

 

CONTRIBUTIONS OF BNIT AND LTIB

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

CONTRIBUTIONS OF LTIB, NCI

 

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CONTRIBUTIONS OF DCTD, CTEP, NCI

 

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CONTRIBUTIONS OF BNIT

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

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DESCRIPTION OF RELATED NCI-BNIT AGREEMENTS AND INTELLECTUAL PROPERTY OF THE PARTIES

 

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PATENTS/PATENT APPLICATIONS

 

BNIT patent rights

 

Below is a representative listing of patents and patent applications of BN which relate to the research under this CRADA.

 

1)   U.S. Patent No. 6,440,422, entitled “Recombinant MVA Virus And The Use Thereof.” Inventors: Sutter et al.

 

2)   PCT Application No. PCT/EP03/05045, entitled “Intergenic Regions As Insertion Sites In The Genome Of Modified Vaccinia Virus Ankara (MVA).”  Inventors: Howley et al.

 

3)   U.S. Patent No. 6,761,893, entitled “Modified Vaccinia Ankara Virus Variant.”  Inventors: Chaplin et al.

 

4)   U.S. Patent No. 6,682,742, entitled “Vector for Integration of Heterologous Sequences Into Poxviral Genomes.”  Inventors: Wintersperger et al.

 

5)   U.S. Patent No. 6,682,743, entitled “Altered Strain Of The Modified Vaccinia Virus Ankara (MVA).”  Inventor: Anton Mayr

 

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6)   U.S. Patent No. 6,924,137, entitled “Method For Virus Propagation.” Inventors: Howley et al.

 

7)   U.S. Patent No. 7,094,412, entitled “Poxvirus Containing Formulations And Process For Preparing Stable Poxvirus Containing Compositions.” Inventors: Howley et al.

 

8)   U.S. Patent No. 7,056,723, entitled “Method For The Recovery And Purification Of Poxviruses From Infected Cells.” Inventors: Heller et al.

 

9)   PCT Patent Application No. PCT/EP03/09704, entitled “Method For The Cultivation Of Primary Cells And For The Amplification Of Viruses Under Serum Free Conditions.” Inventors: Rathe et al.

 

10) U.S. Provisional Patent Application No. 60/924,413, entitled “Affinity-Purification of Vaccinia Virus and Recombinant Vaccinia Virus-Based Vaccines.”

 

11) PCT Patent Application No. PCT/US2007/021436, entitled “Methods for treating cancer with MVA.” Inventors: Delcayre et al.

 

12) U.S. Provisional Patent Application No. 60/960,893, entitled “Use Of MVA To Treat Prostate Cancer.”

 

NCI Patent Applications

 

A Federal Register notice was advertised on November 15, 2007, announcing the NIH’s intent to grant an exclusive license to BNIT.  The prospective exclusive license territory is worldwide and the field of use is limited to the development of therapies for prostatic diseases.  For the avoidance of doubt, said delivery formulation specifically excludes canary poxvirus vectors, NYVAC, eukaryotic expression vectors, aqueous-based delivery formulations and recombinant yeast.  The following patents and patent applications are in the prospective exclusive license:

 

1.                                      U.S. Patent No. 6,946,133 issued September 20, 2005 and U.S. Patent Application No.11/606, 929 filed December 1, 2006, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-062-1996/0], entitled “PROSTATE SPECIFIC ANTIGEN OLIGO-EPITOPE PEPTIDE.” Inventors: Jeffrey Schlom, Kwang Y. Tsang, and Sam Zaremba.

 

2.                                      U.S. Patent Application Nos. 60/334,669 and 10/497,003 filed November 30, 2001 and August 24, 2004, respectively, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-124-2001/0,1], entitled “PEPTIDE AGONISTS OF PROSTATE-SPECIFIC ANTIGEN, AND USES THEREFOR.”  Inventors: Jeffrey Schlom and Kwong Y. Tsang.

 

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3.             U.S. Patent No. 6,165, 460 issued December 26, 2000 and U.S. Patent Application No. 09/693,121 filed October 20, 2000, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No E-200-1990/4], entitled “GENERATION OF IMMUNE RESPONSES TO PROSTATE SPECIFIC ANTIGEN (PSA).” Inventors: Jeffrey Schlom and Dennis L. Panicali.

 

The following list of NIH patents and patent applications are also contained within this prospective license on a non-exclusive basis:

 

1.                                      U.S. Patent No. 6,969,609 issued November 29, 2005; U.S. Patent No. 7,211,432 issued May 1, 2007; U.S. Patent Application No. 11/723,666 filed March 21, 2007; as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-256-1998/0].

 

2.                                      U.S. Patent Application Nos. 08/686,280 filed July 25, 1996 and 08/686,281 filed July 25, 1996 as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-259-1994/3, 4].

 

3.                                      U.S. Patent Nos. 6,893,869, 6,548,068 and 6,045,802 issued May 17, 2005, April 15, 2003 and April  4, 2000 respectively, as well as issued and pending foreign counterparts [HHS Ref. Nos. E-260-1994/1-US-03, US-02, US-01]; and U.S. Patent. Application No. 11/090,686 filed March 8, 2005 [HHS Ref. No E-260-1994/1-US-04].

 

4.                                      U.S. Patent Application Nos. 60/211,717 and 10/297,168 filed June 15, 2000 and August 16, 2003 respectively, as well as all continuations, divisionals, and foreign counterparts [HHS Ref. No. E-187-2000/0].

 

5.                                      U.S. Patent Application Nos. 60/448,591 and 10/543,944 filed February 20, 2003 and February 20, 2004 respectively, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-028-2007/0].

 

6.                                      U.S. Patent No. 6,699,475 issued March 2, 2004, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-134-2007/0].

 

7.                                      U.S. Patent No. 5,093,258 issued March 3, 1992, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-135-2007/0].

 

8.                                      U.S. Patent Application No. 07/205,189 filed June 10, 1988, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-136-2007].

 

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9.                                      U.S. Patent Application No. 60/625,321 filed November 5, 2004, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-138-2007].

 

10.                               U.S. Patent Application No. 07/340,052 filed April 18, 1989, as well as all continuations, divisionals, and issued and pending foreign counterparts [HHS Ref. No. E-147-2007].

 

REFERENCES

 

Prior LTIB, NCI published studies involving recombinant poxviruses

 

Preclinical:

 

Mostböck S, Vidal S, Schlom J, and Sabzevari H. Enhanced levels of costimulation lead to reduced effector/memory CD8+ T cell functionality. J. Immunol. 179:3524-3534, 2007.

 

Kudo-Saito C, Garnett CT, Wansley EK, Schlom J, and Hodge JW. Intratumoral delivery of vector mediated IL-2 in combination with vaccine results in enhanced T-cell avidity and anti-tumor activity. Cancer Immunol. Immunother. 56:1897-1910, 2007.

 

Chakraborty M, Schlom J, and Hodge JW. The combined activation of positive costimulatory signals with modulation of a negative costimulatory signal for the enhancement of vaccine mediated T-cell responses.Cancer Immunol. Immunother. 56:1471-1484, 2007.

 

Kudo-Saito C, Wansley EK, Gruys ME, Wiltrout R, Schlom J and Hodge J. Combination therapy of an orthotopic renal cell carcinoma model employing intratumoral vector-mediated costimulation and systemic IL-2. Clin. Cancer Res. 13:1936-1946, 2007.

 

Palena C, Foon KA, Panicali D, Yafal AG, Chinsangaram J, Hodge JW, Schlom J, and Tsang KY. A potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules. Blood 106:3515-3523, 2005.

 

Yang S, Hodge JW, Grosenbach DW, and Schlom J. Vaccines with enhanced costimulation maintain high avidity memory CTL. J. Immunol. 175:3715-3723, 2005.

 

Yang S, Tsang KY, and Schlom J. Induction of higher avidity human CTL by vector-mediated enhanced costimulation of antigen-presenting cells. Clin Cancer Res. 11:5603-5615, 2005.

 

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Kudo-Saito C, Schlom J, Camphausen K, Coleman CN, and Hodge JW. The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors. Clin Cancer Res. 11:4533-4544, 2005.

 

Hodge JW, Chakraborty M, Kudo-Saito C, Garnett CT, and Schlom J. Multiple costimulatory modalities enhance CTL avidity. J. Immunol. 174:5994-6004, 2005.

 

Kudo-Saito C, Schlom J, and Hodge JW. Induction of an antigen cascade by diversified subcutaneous/                      intratumoral vaccination is associated with antitumor responses. Clin. Cancer Res. 11:2416-2426, 2005.

 

Tsang K-Y, Palena C, Yokokawa J, Arlen PM, Gulley JL, Mazzara GP, Gritz L, Gómez Yafal A, Ogueta S, Greenhalgh P, Manson K, Panicali D, and Schlom J. Analyses of recombinant vaccinia and fowlpox vaccine vectors expressing transgenes for two human tumor antigens and three human costimulatory molecules. Clin. Cancer Res. 11:1597-1607, 2005.

 

Reali E, Canter D, Zeytin H, Schlom J, Greiner JW. Comparative studies of avipox-GM-CSF versus recombinant GM-CSF protein as immune adjuvants with different vaccine platforms. Vaccine 23: 2909-2921, 2005.

 

Slavin-Chiorini DC, Catalfamo M, Kudo-Saito C, Hodge JW, Schlom J, and Sabzevari H. Amplification of the lytic potential of effector/memory CD8+ cells by vector-based enhancement of ICAM-1 (CD54) in target cells: implications for intratumoral vaccine therapy. Cancer Gene Ther. 11:665-680, 2004.

 

Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, and Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine mediated T-cell killing. Cancer Res. 64:4328-4337, 2004.

 

Zeytin HE, Patel AC, Rogers CJ, Canter D, Hursting SD, Schlom J, and Greiner JW. Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (Celecoxib) elicits anti-tumor immunity and long-term survival in CEA.Tg/Min mice. Cancer Res. 64:3668-3678, 2004.

 

Palena C, Zhu M-Z, Schlom J, and Tsang K-Y. Human B cells that hyperexpress a triad of costimulatory molecules via avipoxvector infection: an alternative source of efficient antigen-presenting cells. Blood 104:192-199, 2004.

 

Kudo-Saito C, Schlom J, and Hodge JW. Intratumoral vaccination and diversified subcutaneous/intratumoral vaccination with recombinant poxviruses encoding a tumor antigen and multiple costimulatory molecules. Clin. Cancer Res. 10:1090-1099, 2004.

 

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Hodge JW, Poole DJ, Aarts WM, Gomez Yafal A, Gritz L, and Schlom J. Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses. Cancer Res. 63:7942-7949, 2003.

 

Arlen PM, Gulley JL, Palena C, Marshall J, Schlom J, and Tsang K-Y. A novel ELISPOT assay to enhance detection of antigen-specific T cells employing antigen-presenting cells expressing vector-driven human B7-1. J. Immunol. Meth. 279:183-192, 2003.

 

Grosenbach DW, Schlom J, Gritz L, Yafal AG, and Hodge JW. A recombinant vector expressing transgenes for four T-cell costimulatory molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4+ and CD8+ T-cell activation, protection from apoptosis and enhanced cytokine production. Cell. Immunol. 222:45-57, 2003.

 

Hodge JW, Grosenbach DW, Aarts Wm, Poole DJ, and Schlom J. Vaccine therapy of established tumors in the absence of autoimmunity. Clin. Cancer Res. 9:1837-1849, 2003.

 

Greiner J, Zeytin H, Anver MR, and Schlom J. Vaccine-based therapy directed against carcinoembryonic antigen demonstrates antitumor activity on spontaneous intestinal tumors in the absence of autoimmunity. Cancer Res. 62:6944-6951, 2002.

 

Tatari-Calerone Z, Semnani RT, Nutman, TB, Schlom J, and Sabzevari H. Acquisition of CD80 by human T cells at early states of activation: functional involvement of CD80 acquisition in T-cell to T-cell interaction. J. Immunol. 169:6162-6169, 2002.

 

Aarts WM, Schlom J, and Hodge JW. Vector-based vaccine/cytokine combination therapy to enhance induction of immune responses to a self-antigen and anti-tumor activity. Cancer Res. 62:5770-5777, 2002.

 

Terasawa H, Tsang Kwong-Yok, Gulley J, Arlen P, and Schlom J. Identification and characterization of a human agonist CTL epitope of human prostate-specific antigen. Clin. Cancer Res. 8: 41-53, 2002.

 

Shankar P, Schlom J, and Hodge JW. Enhanced activation of Rhesus T cells by vectors encoding a triad of costimulatory molecules (B7-1, ICAM-1, LFA-3). Vaccine 20: 744-755, 2001.

 

Tsang KY, Zhu MZ, Even J, Gulley J, Arlen P, and Schlom J. The infection of human dendritic cells with recombinant avipox vectors expressing a costimulatory molecule transgene (CD80) to enhance the activation of antigen-specific cytolytic T cells. Cancer Res. 61: 7568-7576, 2001.

 

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Zhu MZ, Terasawa H, Gulley J, Panicali D, Arlen P, Schlom J, and Tsang KY.  Enhanced activation of human T cells via avipox vector-mediated hyperexpression of a triad of costimulatory molecules in human dendritic cells. Cancer Res. 61: 3725-3734, 2001.

 

Hodge JW, Grosenbach DW, Rad AN, Giuliano M, Sabzevari H, and Schlom J. Enhancing the potency of peptide-pulsed antigen presenting cells by vector-driven hyperexpression of a triad of costimulatory molecules. Vaccine 19: 3552-3567, 2001.

 

Grosenbach DW, Barrientos JC, Schlom J, and Hodge JW.  Synergy of vaccine strategies to amplify antigen-specific immune responses and anti-tumor effects. Cancer Res. 61: 4497-4505, 2001.

 

Sabzevari H, Kantor J, Jaigirdar A, Tagaya Y, Naramura M, Hodge JW, Bernon J, and Schlom J. Acquisition of CD 80 (B7-1) by T cells. J. Immunol. 166: 2505-2513, 2001.

 

Kass E, Panicali DL, Mazzara G, Schlom J, and Greiner, JW. Granulocyte/macrophage colony-stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant. Cancer Res. 61: 206-214, 2001.

 

Arlen P, Tsang KY, Marshall JL, Chen A, Steinberg SM, Poole D, Horan Hand P, Schlom J, and Hamilton JM. The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines. Cancer Immunol. Immunother. 49: 517-529, 2000.

 

Hodge JW, Rad AN, Grosenbach DW, Sabzevari H, Yafal AG, Gritz L, and Schlom J. Enhanced activation of T cells by dendritic cells engineered to hyperexpress a triad of costimulatory molecules. J. Natl. Cancer Inst. 92: 1228-1239, 2000.

 

Kass E, Parker J, Schlom J, and Greiner JW. Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen presenting cells in regional lymph nodes. Cytokine 12: 960-971, 2000.

 

Freund YR, Mirsalis JC, Fairchild DG, Brune J, Hokama LA, Schindler-Horvat J, Tomaszewski JE, Hodge JW, Schlom J, Kantor JA, Tyson CA, and Donohue SJ. Vaccination with a recombinant vaccinia vaccine containing the B7-1 co-stimulatory molecule causes no significant toxicity and enhances T cell-mediated cytotoxicity. Int. J. Cancer 85: 508-517, 2000.

 

Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MGO, and Schlom J. A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res. 59: 5800-5807, 1999.

 

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Hodge JW and Schlom J. Comparative studies of a retrovirus versus a poxvirus vector in whole-tumor-cell vaccines. Cancer Res. 59: 5106-5111, 1999.

 

Tsang KY, Zhu MZ, Nieroda CA, Correale P, Zaremba S, Hamilton JM, Cole D, Lam C, and Schlom J. Phenotypic stability of a cytotoxic T-cell line directed against an immuno-dominant epitope of human carcinoembryonic antigen. Clin. Cancer Res. 3: 2439-2449, 1997.

 

McLaughlin JP, Abrams S, Kantor J, Schlom J, and Greiner JW. Immunization with a syngeneic tumor infected with recombinant vaccinia virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) induces tumor regression and long-lasting systemic immunity. J. Immunother. 20: 449-459, 1997.

 

Hodge JW, McLaughlin JP, Kantor JA, and Schlom J. Diversified prime and boost protocols using recombinant vaccinia virus and recombinant nonreplicating avian pox virus to enhance T-cell immunity and antitumor responses. Vaccine 15: 759-768, 1997.

 

Akagi J, Hodge JW, McLaughlin JP, Gritz L, Panicali D, Kufe D, Schlom J, and Kantor J. Therapeutic antitumor response after immunization with an admixture of recombinant vaccinia viruses expressing a modified MUC1 gene and the murine T-cell costimulatory molecule B7. J. Immunother. 20: 38-47, 1997.

 

McLaughlin JP, Schlom J, Kantor JA, and Greiner J. Improved immunotherapy of a recombinant CEA vaccinia vaccine when given in combination with Interleukin-2. Cancer Res. 56: 2361-2367, 1996.

 

Hodge JW, McLaughlin JP, Abrams S, Shupert WL, Schlom J, and Kantor JA. Admixture of a recombinant vaccinia virus containing the gene for the costimulatory molecule B7 and a recombinant vaccinia virus containing a tumor associated antigen gene results in enhanced specific T-cell responses and antitumor immunity. Cancer Res. 55: 3598-3603, 1995.

 

Hodge JW, Donohue SJ, Levine BS, Wheeler CW, Panicali D, Schlom J, and Kantor JA. A recombinant vaccinia virus expressing human prostate-specific antigen (PSA): Safety and immunogenicity in a nonhuman primate. Int. J. Cancer 63: 231-237, 1995.

 

Karr JF, Kantor JA, Horan Hand P, Eggensperger DL, and Schlom J. Presence of prostate-specific antigen (PSA) gene in primates and the expression of recombinant human PSA in a transfected murine cell line. Cancer Res. 55: 2455-2462, 1995.

 

Hodge JW, Abrams S, Schlom J, and Kantor J. Induction of antitumor immunity by

 

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recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res. 54: 5552-5555, 1994.

 

Clinical:

 

Schlom J, Arlen PM, and Gulley JL. Cancer vaccines:  moving beyond current paradigms. Clin. Cancer Res. 13:3776-3782, 2007.

 

Arlen PM, Skarupa L, Pazdur M, Seetharam M, Tsang KY, Grosenbach DW, Feldman J, Poole DJ, Litzinger M, Steinberg SM, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, and Gulley JL. Clinical safety of a viral vector-based prostate cancer vaccine strategy. J. Urol. 178: 1515-1520, 2007

 

Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, and Dahut W. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen independent prostate cancer. Clin Cancer Res 12:1260-1269, 2006.

 

Kaufman HL, Cohen S, Cheung K, DeRaffele, Mitcham J, Moroziewicz D, Schlom J, and Hesdorffer C. Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors. Human Gene Ther. 17:239-244, 2006.

 

Arlen PM, Gulley JL, Todd N, Lieberman R, Steinberg SM, Morin S, Bastian A, Marte J, Tsang K-Y, Beetham P, Grosenbach DW, Schlom J, and Dahut W. Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. J. Urol. 174:539-546, 2005.

 

Gulley JL, Arlen PM, Bastian A, Morin S, Marte J, Beetham P, Tsang K-Y, Yokokawa J, Hodge JW, Ménard C, Coleman CN, Camphausen K, Sullivan F, Steinberg SM, Schlom J, and Dahut W. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin. Cancer Res. 11:3353-3362, 2005.

 

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Kaufman HL, Wang W, Manola J, DiPaola RS, Ko YJ, Sweeny C, Whiteside TL, Schlom J, Wilding G, Weiner LM.  Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897):  A trial of the eastern cooperative oncology group.  J. Clin. Oncol.  22: 2122-2132, 2004.

 

Marshall J, Gulley JL, Arlen PM, Beetham PK, Tsang KY, Slack R, Hodge JW, Doren S, Grosenbach DW, Hwang J, Fox E, Odogwa L, Park S, Panicali D, Schlom J. A phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM (B7-1/ICAM-1/LFA-3) alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without GM-CSF, in patients with CEA-expressing carcinomas. J. Clin. Oncol. 23:720-731, 2005.

 

Gulley J, Chen AP, Dahut W, Arlen PM, Bastian A, Steinberg SM, Tsang K, Panicali D, Poole D, Schlom J, and Hamilton JM. A Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer. The Prostate 53:109-117, 2002.

 

Marshall JL, Hoyer RJ, Toomey MA, Faraguna K, Chang P, Richmond E, Pedicano JE, Gehan E, Peck RA, Arlen P, Tsang KY, and Schlom J. Phase I study in advanced cancer patients of a diversified prime and boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J. Clin. Oncol. 18: 3964-3973, 2000.

 

Eder JP, Kantoff PW, Roper K, Xu G, Bubley GJ, Boyden J, Oh WK, Horzempa ML, Arlen P, Tsang A, Panicali D, Schlom J, and Kufe DW. A phase I trial of a recombinant vaccinia virus expressing prostate specific antigen in advanced prostate cancer. Clin. Cancer Res. 6: 1632-1638, 2000.

 

Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, and Schlom J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia vaccine. J. Natl. Cancer Inst. 87: 982-990, 1995.

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

APPENDIX B

 

STAFFING, FUNDING AND MATERIALS/EQUIPMENT CONTRIBUTIONS
 OF THE PARTIES

 

Staffing Contributions:

 

ICD will provide scientific staff and other support necessary to conduct the research and other activities described in the Research Plan.  ICD’s scientific staff will include ICD’s CRADA Principal Investigator and technical staff.

 

ICD estimates that [***] person-years of effort per year will be required to complete the CRADA research.

 

Collaborator will provide scientific staff and other support necessary to conduct the research and other activities described in the Research Plan.  Collaborator’s scientific staff will include Collaborator’s Principal Investigator and technical staff.

 

Collaborator estimates that [***] person-years of effort per year will be required to complete the CRADA research.

 

Funding Contributions:

 

Collaborator agrees to provide funds in the amount of $[***] per year of the CRADA to ICD.  CRADA funds shall be used in support of this CRADA for technical, statistical, and administrative support for the research, including but not limited to:  (a) reagents, supplies, equipment, and other materials associated with experiments related to the CRADA; (b) salaries for nonpermanent employees; and (c) travel for CRADA-related activities.  Collaborator will provide funds in equal annual installments of $[***].  The first installment will be due within thirty (30) days of the Effective Date.  Each subsequent installment will be due within thirty (30) days of each anniversary of the Effective Date.  Collaborator agrees that ICD can allocate the funding between the various categories in support of the CRADA research as ICD’s CRADA PI sees fit.

 

CRADA PAYMENTS:

 

Collaborator will make payments by check as provided below.  Collaborator will make checks payable to the NCI, will reference the CRADA number and title on each check , and will send checks via trackable mail or courier to:

 

CRADA Funds Coordinator

National Cancer Institute

Technology Transfer Center

6120 Executive Blvd., Suite 450

Rockville, MD  20852-7181

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

CRADA Travel Payments:

 

Travel arrangements for all Government staff will be made in accordance with the Federal Travel Rules and Regulations, whether arranged by ICD and funded using either appropriated funds or CRADA funds, or arranged and funded directly by Collaborator.

 

Clinical Data Collection Support:

 

CTEP/DCTD utilizes the contract services of two companies for assistance in the monitoring of DCTD-sponsored clinical trials. Collaborator will be responsible for making arrangements directly with the appropriate DCTD contractors to receive reports from DCTD-sponsored trials. This will include quarterly reports, Adverse Event reports and summary reports. The contractor for the Phase 2 and 3 studies will provide these reports electronically in a format compatible with Collaborator’s database at a cost of $[***] per year, payable directly to the contractor.  The NCI Phase 1 contractor will also provide reports directly to Collaborator. Contact information for each of the DCTD contractors will be provided as needed. Any arrangement which involves the collection of more than the summarized data (Summary Data) provided annually to the DCTD will be at the expense of the Collaborator.

 

Collaborator may make only reasonable requests for access to Clinical Data and Results and Raw Data or any other information that is in the possession of extramural investigators.  The information will be provided according to a mutually agreed upon plan between the NCI, the Collaborator, and the investigator(s), and only in accordance with the guidelines and policies of the responsible Data Monitoring Committee.  Collaborator will be responsible for the costs associated with any unusually burdensome requests, such as a request that the data be provided in a format which is different than that normally collected. Should Collaborator choose to review copies of patient research records, such a review will be at Collaborator expense and occur after agreement and notification of the investigators by NCI and only after all patient identifiers have been removed.

 

Support for IB Preparation, Distribution, IND and IND Amendments:

 

CTEP/DCTD utilizes the contract services of two companies for assistance in the distribution of the IND, IND amendments and Investigator Brochures (IBs) for DCTD-sponsored clinical trials. Collaborator will be responsible for the costs associated with providing copies of the IBs to NCI registered investigators participating in clinical trials which are part of this CRADA, as well as the costs associated with the receipt of the IND and IND amendments. Collaborator will make arrangements directly with each DCTD contractor and will be invoiced directly by the contractor as described below.

 

The payments will be as follows:

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

IB Preparation (if performed by ICD):

 

Collaborator will be responsible for the costs associated with the preparation and updating of the IB. Collaborator will make arrangements directly with the DCTD contractor.

 

IB distribution:

 

Collaborator will be invoiced annually for the costs associated with IB distribution and payment will be expected within 30 days of receipt of each invoice. Collaborator agrees to provide funds for distribution of all IBs.  Typical costs, which are subject to change for the distribution of 10 IBs is $[***], $[***] for [***] IBs, and $[***] for [***] IBs.

 

IND amendments:

 

Collaborator will be invoiced quarterly for the costs associated with preparing, submitting, and distributing copies of IND Amendments to the Collaborator, and payment will be expected within 30 days of receipt of each invoice. Collaborator agrees to provide funds for all IND amendments. The costs, which are subject to change, will be as follows:

 

1.             IND Amendment (volume up to 100 pages): $[***]

2.             IND Amendment (amendment volume exceeding 100 pages): $[***]

3.             IND:  $[***]

 

Materials/Equipment Contributions:

 

ICD will provide the following ICD Materials, information and data to Collaborator:

 

[***]

 

[***]

 

[***]

 

[***]

 

B-3

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

[***]

 

[***]

 

[***]

 

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CONFIDENTIAL
    	
NCI — BN   ImmunoTherapeutics CRADA #2377
    

 

PUBLIC HEALTH SERVICE

COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

FOR EXTRAMURAL-PHS CLINICAL RESEARCH

 

APPENDIX C

 

MODIFICATIONS TO THE MODEL EXTRAMURAL-PHS CLINICAL CRADA
 (Additions are indicated by underline, deletions by strike-out)

 

Amend or add the following definitions in Article 2:

 

“Confidential Information” means confidential scientific, business, financial information, or Identifiable Private Information provided that Confidential Information does not include:

 

(a)           information that is publicly known or that is available from public sources;

 

(b)                                 information that has been made available by its owner to others without a confidentiality obligation;

 

(c)                                  information that is already known by the receiving Party, or information that is independently created or compiled by the receiving Party without reference to or use of the provided information; or

 

(d)                                 information that relates to potential hazards or cautionary warnings associated with the production, handling, or use of the subject matter of the Research Plan.

 

The Parties agree that Collaborator’s Confidential Information includes information provided by Affiliates of Collaborator, including Bavarian Nordic A/S and Bavarian Nordic GmbH.

 

“Contract” means a Funding Agreement that is a research and development mechanism that provides that the contractor perform for the benefit of the Government, with an expectation of completion of the stated research goals and the delivery of a report, data, materials or other product. Generally, Contracts are administered under the Federal Acquisition Regulations (FAR) codified at Title 48 C.F.R., Chapter 1 or the Health Services Acquisition Regulations (HSAR) codified at Title 48 C.F.R., Chapter 3.

 

Cooperative Research and Development Agreement” or “CRADA” means this Agreement, entered into pursuant to the Federal Technology Transfer Act of 1986, as amended (15 U.S.C. §§ 3710a et seq.), and Executive Order 12591 of April 10, 1987.  For purposes of clarity and avoidance of disputes, the Parties agree that this Agreement is not a Contract, Cooperative Agreement, Funding Agreement or Grant.

 

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“Cooperative Agreement” means a Funding Agreement that is a species of a Grant, whereby the funding Federal agency intends to be substantially involved in carrying out the research program.

 

“CRADA Data” means information developed by or on behalf of the Parties in during the performance of the Research Plan, including  Summary Data and Clinical Data in ICD’s Possession and Control, but excluding Raw Data (that is not otherwise Clinical Data in ICD’s Possession and Control).

 

“CTA” means Clinical Trial Agreement.

 

“CTEP” means the Cancer Therapy Evaluation Program, DCTD, NCI, a program within NCI which plans, assesses and coordinates all aspects of clinical trials including extramural clinical research programs, internal resources, treatment methods and effectiveness, and compilation and exchange of data.

 

“DTP” means Developmental Therapeutics Program, DCTD, NCI, the program within the NCI which coordinates pre-clinical development of agents to be evaluated in DCTD-sponsored clinical trials.

 

“DCTD” means Division of Cancer Treatment and Diagnosis, NCI.

 

“FDA” means U.S. Food and Drug Administration.

 

“Funding Agreement” means a Contract, Grant, or Cooperative Agreement entered into between a Federal agency and another party for the performance of experimental, developmental or research work funded in whole or in part by the Federal Government.

 

“Grant” means a Funding Agreement that is an award of financial assistance which may be provided for support of basic research in a specific field of interest to the funding Federal agency.

 

“Multi-Party Data” means clinical data from clinical studies sponsored by NCI pursuant to CTAs or CRADAs, where such data are collected under protocols involving combinations of investigational agents from more than one CTA or CRADA collaborator.

 

“Protocol Review Committee” (or “PRC”) means the CTEP/DCTD committee that reviews and approves studies involving NCI investigational agents and/or activities supported by NCI.

 

“Test Article” means, in accordance with 21 C.F.R. § 50.3(j), any drug (including a biological product), medical device, food additive, color additive, electronic product, or any other article subject to regulation under the Federal Food, Drug, and Cosmetic Act that is intended for administration to humans or animals, including a drug or biologic as identified in the Research

 

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Plan and Appendix B, that is used within the scope of the Research Plan.  The Test Article may also be referred to as Investigational Agent, Study Material, or Study Product. is further characterized below as “Investigational Agent”, “PROSTVAC VF”, CRADA Materials or “Research Agent”, depending on the regulatory stage of Test Article in the product development process.

 

Under this Agreement, the Test Article to be studied in clinical trials pursuant to the Research Plan is also referred to as the “Investigational Agent.”  The Investigational Agent is PROSTVAC VF, a vaccine for the treatment of prostate cancer comprised of the combination of (i) PSA/TRICOM in a recombinant vaccinia virus vector and (ii) PSA/TRICOM in a recombinant fowlpox vector.

 

Under this Agreement, the Test Article to be studied in pre-clinical studies (not in humans) is referred to as the “Research Agent.”  The Research Agent is recombinant pox virus based prostate cancer vaccines and is also CRADA Materials.  In the event that, during the term of this CRADA, the parties mutually agree to advance one or more Research Agents to clinical trials in Human Subjects, the parties will negotiate in good faith appropriate amendments to this CRADA.

 

For purposes of clarity, the parties agree that the Investigational Agent does not include MVA-BN® or any agent proprietary to a third party in a Multi Party study pursuant to Article 8.9. Test Article as defined above is not CRADA Materials.

 

Amend Article 3.1

 

3.1          Performance of Research and Development.  The research and development activities to be carried out under this CRADA will be performed by the Parties in accordance with the Research Plan identified on the Cover Page, as well as and by ICD’s contractors or grantees as described in the Research Plan.  However, ICD’s contractors or grantees are not Parties to the CRADA, and this CRADA does not grant to Collaborator any rights to Inventions made by ICD’s contractors or grantees.  Notwithstanding the forgoing, ICD will include provisions granting Collaborator those rights described in CTEP’s Intellectual Property Option to Collaborators in each Funding Agreement for clinical studies conducted by an extramural Clinical Investigator(web site: http://ctep.cancer.gov/industry). The CRADA PIs will be responsible for coordinating the scientific and technical conduct of this project on behalf of their employers.  Any Collaborator employees who will work at ICD facilities will be required to sign a Guest Researcher or Special Volunteer Agreement appropriately modified in view of the terms of this CRADA.

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Amend Article 3.3

 

3.3          Use and Disposition of Collaborator Materials and ICD Materials.  Except as otherwise provided in this Section 3.3, Tthe Parties agree to use Collaborator Materials, Test Articles, and ICD Materials only in accordance with the Research Plan and Protocol(s), not to transfer these materials to any third parties except in accordance with the Research Plan and Protocol(s) or as approved by the owning or providing Party, and, upon expiration or earlier termination of this CRADA, to dispose of these materials as directed by the owning or providing Party.

 

Notwithstanding the foregoing, within [***] following the Effective Date, ICD will execute a Notification of Change in Sponsorship, related FDA 1571 Forms, and any other documents required by law to transfer to Collaborator sponsorship of the following for the clinical development and commercialization of Licensed Products and Licensed Processes in the Licensed Field of Use, as those terms are defined in the Patent License Agreement — Exclusive License between PHS and Collaborator (HHS Ref. No. A-332-2007) executed contemporaneously with this CRADA (the “Patent License”):

 

1.              BB-MF 10428 PROSTVAC-VF, Serial #0077; and

2.              BB-MF 5537 (PROSTVAC), 6670 (PROSTVAC), 7421 (rF-PSA); 7646 (PROSTVAC).

 

In the event of the termination of the Patent License prior to the expiration of its term, Collaborator will execute a Notification of Change in Sponsorship, related FDA 1571 Forms, and any other documents required by law to transfer to ICD sponsorship of the INDs and DMFs.

 

Further notwithstanding the foregoing, ICD hereby grants to Collaborator (and its Affiliates, sub-licensees and contractors), and Collaborator accepts a non-exclusive, worldwide, royalty-free license in and to the PROSTVAC Materials (as defined below) to research, develop, make, have made, and use the PROSTVAC Materials. The foregoing license shall not include the right to distribute or sell the PROSTVAC Materials alone to any third party (except for permitted distribution to Affiliates, sub-licensees and contractors) and shall terminate in the event of the termination of the Patent License prior to the expiration of its term.  For the avoidance of doubt, the restriction on the distribution/sale of PROSTVAC Materials alone does not apply to vaccines used in the treatment of prostatic disease, or Licensed Products or Licensed Processes where PROSTVAC Materials are used in combination with Collaborator Materials.  Upon expiration of the Patent License, on a country-by-country basis, the license provided in this paragraph shall be irrevocable.  The foregoing license is predicated on the execution of the Patent License currently under negotiation between Collaborator and NIH (HHS Ref. No. A-332-2007).

 

In addition, until the expiration or earlier termination of this CRADA, ICD shall not transfer any aliquots of the PROSTVAC seed banks, aliquots of PROSTVAC master cell cultures, or any information specific to PROSTVAC to any third party, except for research purposes, in

 

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accordance with the Research Plan and related protocols.  The Parties acknowledge that ICD can share with third parties poxvirus manufacturing know-how in the possession of ICD at the initiation of the CRADA.

 

On and after the expiration or earlier termination of this CRADA and until the expiration or earlier termination of the Patent License, any transfer by ICD to a third party of any aliquots of the PROSTVAC seed banks, aliquots of  PROSTVAC master cell cultures, or any information specific to PROSTVAC shall be for research purposes only. ICD will insure that any transferee is informed of and agrees to the foregoing restrictions.  For purposes of this paragraph, the PROSTVAC seed banks, PROSTVAC master cell cultures or information specific to PROSTVAC means those materials and  information referred to in Appendix B at items 2(a) — (d)) and 3(d), with the exclusion of poxvirus manufacturing know-how, in each case under the heading “Materials/Equipment Contributions.”

 

For purposes of clarity and avoidance of disputes, the rights granted herein to the INDs and the PROSTVAC Materials shall not terminate upon the expiration or earlier termination of this CRADA.

 

“PROSTVAC Materials” means the materials and information listed in Appendix B, Materials/Equipment Contributions, sections 2 and 3 as those sections describe ICD Materials being supplied under the CRADA.

 

Promptly following the Effective Date, the Parties will work diligently to transfer the PROSTVAC Materials to Collaborator.

 

The Parties acknowledge that there may be materials or information related to PROSTVAC in addition to that listed in Appendix B which is necessary or useful for the research, development or commercialization of Licensed Products or Licensed Processes.  In that event, upon request of Collaborator, ICD and Collaborator will work together in good faith to provide such materials or information or access thereto to Collaborator, including executing documents of authorization or permission, and such additional materials or information shall be deemed to be PROSTVAC Materials hereunder.

 

Amend Article 3.6

 

3.6          Clinical Investigator Responsibilities.  The Clinical Investigator will be required to submit, or to arrange for submission of, each Protocol associated with under this CRADA for the study of the Investigational Agent in Human Subjects to all appropriate IRBs, and for ensuring that the IRBs are notified of the role of Collaborator in the research.  In addition to the Protocol all associated documents, including informational documents and advertisements, must be reviewed and approved by the appropriate IRB(s) before starting the research at each Clinical Research Site.  The research will be done in strict accordance with the Protocol(s) and no

 

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substantive changes in a finalized Protocol will be made unless mutually agreed upon, in writing, by the Parties.  Research will not commence (or will continue unchanged, if already in progress) until each substantive change to a Protocol, including those required by either the FDA or the IRB, has been integrated in a way acceptable to the Parties, submitted to the FDA (if applicable) and approved by the appropriate IRBs.

 

Amend Article 3.7

 

3.7          Investigational New Drug Applications.

 

3.7.1       If an IND is required either ICD or Collaborator, DCTD, NCI, as indicated in the Research Plan, will prepare and submit an IND, sponsor clinical trials that are subject to this CRADA, and all Clinical Investigators participating in DCTD-sponsored clinical trials must have completed registration documents on file (1572 forms) with CTEP.

 

3.7.2       If ICD elects to file its own IND, To support the DCTD IND, Collaborator agrees to provide ICD DCTD with background data and information necessary to support the IND, either directly or by right of cross reference as provided in the next sentence.  Collaborator further agrees to provide a letter of cross-reference to all pertinent regulatory filings including an IND(s) and/or DMF(s) sponsored by Collaborator.  Collaborator’s employees will be reasonably available to respond to inquiries from the FDA regarding information and data contained in the Collaborator’s IND, DMF, other filings, or other information and data provided to ICD DCTD by the Collaborator pursuant to this Article 3.7.  If ICD DCTD has provided information or data to assist Collaborator in its IND filing, ICD DCTD will provide a letter of cross reference to its IND and respond to inquiries related to information provided by ICD DCTD, as applicable.

 

3.7.3       If Collaborator supplies Confidential Information to ICD DCTD in support of an IND filed by ICD DCTD, this information will be protected in accordance with the corresponding confidentiality provisions of Article 8.

 

3.7.4       Collaborator or NCI may sponsor its own clinical trials and hold its own IND for studies which may be performed within or outside the scope of this CRADA and the Research Plan.  Collaborator and ICD shall use reasonable efforts to coordinate the ICD-sponsored studies under this CRADA and the Collaborator-sponsored studies so that these studies do not These studies, however, should not adversely affect the ability to accomplish the goal of the Research Plan or Collaborator’s clinical development plans, for example, by competing for the same study population.  All data from the those clinical trials or studies conducted outside of the scope of the CRADA by Collaborator are

 

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proprietary to Collaborator for purposes of this CRADA.  Collaborator and NCI mutually agree to notify the other party in advance of the initiation by Collaborator or NCI of any clinical study outside of the scope of the CRADA which involves Investigational Agent.

 

3.7.5    In the event that Canadian institutions are participating on DCTD-sponsored clinical trials, Collaborator will need to assist in the submission of the regulatory documents to the Canadian Health Products and Food Branch to allow for such participation. This may include a letter of cross-reference to an existing Clinical Trials Application (CTA) or a DMF, including supporting documentation on the production of the Investigational Agent. The forms and procedures for preparing Canadian CTAs are available at http://www.hc-sc.gc.ca/hpfb-dgpsa/index_e.html.

 

Amend Article 3.8

 

3.8          Research Agent and Test Article Information and Supply.  Collaborator agrees to provide ICD DCTD without charge and on a schedule that will ensure adequate and timely performance of the research, a sufficient quantity of formulated and acceptably labeled, clinical-grade Test Article (and, as required by the Protocol(s), Placebo) to complete the clinical trial(s) agreed to and approved under this CRADA and, as agreed in the Research Plan, a sufficient quantity of Research Agent to complete preclinical studies agreed to and approved under this CRADA.  Collaborator will provide a Certificate of Analysis to ICD DCTD for each lot of the Test Article Investigational Agent provided.  It is understood that DCTD shall take responsibility for and reasonable steps to maintain appropriate records and assure appropriate supply, handling, storage, distribution and usage of these materials in accordance with the terms of this Agreement, the Protocol(s) and any applicable laws and regulations relating thereto.  Notwithstanding the foregoing, ICD acknowledges that Collaborator will be required to develop an appropriate manufacturing process, test such process, and qualify an appropriate manufacturing facility, all as required by the FDA and cGMP, before the manufacture of cGMP Investigational Agent for provision to DCTD can commence, and that the development of an appropriate manufacturing process depends upon the receipt of manufacturing-related information in the possession of ICD.

 

Collaborator agrees to supply sufficient inventory to ensure adequate and timely supply of Investigational Agent for mutually agreed upon Protocol(s). DCTD will provide updated forecasts of amounts of Investigational Agent anticipated for ongoing and anticipated studies.  Collaborator further agrees to provide draft Investigational Agent labels to the NCI Pharmaceutical Management Branch (PMB) for review and agrees to reasonable labeling revisions to comply with DCTD label guidelines.  NCI NSC (National Service Center) numbers will be required to be on the label of Investigational Agent for all DCTD-sponsored clinical trials.

 

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Furthermore, Collaborator agrees to provide without charge Investigational Agent or unformulated analytical grade Investigational Agent or metabolites, if available, to DCTD to supply to NCI investigators for the development of mutually agreed upon analytical assays, ancillary correlative studies and non-clinical studies conducted in conjunction with DCTD-sponsored  protocols.

 

Collaborator agrees to allow Investigational Agent and Research Agent, as provided in the Research Plan, to be distributed to NCI investigators for mutually agreeable non-clinical studies as set forth in the Research Plan designed to enhance the basic understanding and development of Test Articles.  These will include non-clinical studies designed to support clinical trials in pediatric patients; non-clinical combination studies to provide data in support of a clinical trial and other pertinent requests.  All NCI investigators will sign Material Transfer Agreements (MTAs) that acknowledge the proprietary nature of the Test Articles to Collaborator and with respect to Investigational Agent and Research Agents include intellectual property and publication provisions consistent with those in this Agreement and CTEP’s Intellectual Property Option to Collaborator for clinical trials (web site: http://ctep.cancer.gov/industry).

 

Collaborator agrees to provide Investigational Agent and Research Agent to DCTD for DCTD to conduct mutually agreed upon pre-clinical studies (“DCTD Pre-clinical Studies”) as described in the Research Plan aimed at enhancing the understanding of the mechanism of action of Investigational Agent and its targets and optimizing its clinical development program.  DCTD’s work may also include such activities as the development of assays to detect target modulation, biomarker studies, and pharmacodynamic analyses performed in conjunction with the NCI-sponsored clinical studies.  In accordance with this Agreement, DCTD will update Collaborator regarding progress and findings to help ensure optimal designs and avoid duplication. DCTD will inform Collaborator prior to the execution of any DCTD Pre-clinical Studies involving  Investigational Agent or Research Agents.  Collaborator may, at their discretion, provide comment on any of the planned studies. Manuscripts and presentations related to these studies will be handled in accordance with Article 8.7 of this CRADA.

 

The Parties shall agree upon the Party to take the lead in preparing the Investigator’s Brochure (IB) for Investigational Agent.  The Party that does not prepare the IB shall provide the other Party with information in its possession as reasonably requested by the preparing party to support the preparation of   the IB and all subsequent revisions/editions. If DCTD prepares the IB, Collaborator will also be responsible for the costs associated with the preparation of the IB as detailed in Appendix B.  In addition to being filed to the DCTD IND, the IB will be on file in the PMB and will be distributed to all investigators participating on a clinical trial using the Investigational Agent.  Distribution will be accompanied by a statement about the confidentiality of the document and it is anticipated that distribution will be electronic.   All electronic distribution will be done using Adobe Acrobat PDF.  Any IB received by the PMB that is not in this format will be converted before distribution.  Hard copy IBs should be sent to IB Coordinator, Pharmaceutical Management Branch, CTEP, DCTD, NCI, 6130 Executive Blvd, Room 7149, Rockville, MD 20852.  Electronic versions should be emailed to the IB Coordinator 

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

at IBCoordinator@mail.nih.gov.

 

Amend Article 3.9

 

3.9          Test Article Investigational Agent Delivery and Usage.  Collaborator will ship the Test Article Investigational Agent and, if required, Placebo to ICD NCI or its designee in containers marked in accordance with 21 C.F.R. § 312.6.  Any Investigational Agent sent to the NCI Clinical Repository shall be sent from a U.S. facility and not directly from the foreign manufacturer. In other words, the Collaborator will be responsible for importing/shipping of the materials from the foreign manufacturer to their U.S. facility, then to the NCI Clinical Repository.   NCI agrees and will assure that appropriate records of Test Articles are kept and will take reasonable steps to ensure the Investigational Agent is used in accordance with the applicable protocols and FDA regulations.  ICD agrees that the Clinical Investigators will keep appropriate records and take reasonable steps to ensure that the Test Article Investigational Agent is used in accordance with the Protocol(s) and applicable FDA regulations.  In addition, ICD NCI agrees that all Clinical and DCTD Investigators will agree that the Test Article Investigational Agent and Research Agent (and all Confidential Information supplied by Collaborator relating to the Test Article Investigational Agent and Research Agent) will be used solely for the conduct of the CRADA research and development activities.  Furthermore, ICD NCI agrees that no analysis or modification of the Test Article Investigational Agent or Research Agent will be performed without Collaborator’s prior written consent.  At the completion of the Research Plan or when an Investigational Agent or Research Agent supply is no longer suitable for clinical or preclinical use, NCI will assure that any unused quantity of Test Article Investigational Agent and Research Agent will be returned to Collaborator at Collaborator’s expense or disposed of as directed by Collaborator at Collaborator’s expense.  Pharmacy contacts at ICD or its designee will be determined by ICD and communicated to Collaborator. The contact person for NCI will be [***] and the Collaborator contact will be [***]

 

Amend Article 3.10

 

3.10        Monitoring.

 

3.10.1     The Sponsor or its designee DCTD, NCI will be primarily responsible for monitoring clinical sites and for assuring the quality of all clinical data, unless otherwise stated in the Research Plan. Monitoring will comply with FDA Good Clinical Practice (international Conference on Harmonisation (ICH) E6:  Good Clinical Practice:  Consolidated Guidance; 62 Federal Register 25, 691 (1997)). the DCTD guidelines as described on the CTEP website at: http://ctep.cancer.gov/monitoring/index.html. The other Party may also perform quality assurance oversight.  The monitor will communicate significant Protocol violations and submit documentation of monitoring outcomes on Protocol

 

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insufficiencies to the other Party in a timely manner.

 

3.10.2     Subject to the restrictions in Article 8 concerning IPI, and with reasonable advance notice and at reasonable times, ICD DCTD will permit Collaborator or its designee(s) access to laboratories and clinical site(s) to monitor the conduct of the research, as well as.  Collaborator may also make arrangements with DCTD to audit source documents containing Raw Data, at Collaborator’s expense, to the extent necessary to verify compliance with FDA Good Laboratory Practices and Good Clinical Practice, and the Protocol(s).

 

Amend Article 3.11

 

3.11        FDA Meetings/Communications.  All formal meetings with the FDA concerning any clinical trial within the scope of the Research Plan will be discussed by Collaborator and ICD in advance.  Each Party reserves the right to take part in setting the agenda for, to attend, and to participate in these meetings.  The Sponsor will provide the other Party with copies of FDA meeting minutes, all transmittal letters for IND submissions, IND safety reports, formal questions and responses that have been submitted to the FDA, Annual Reports, and official FDA correspondence, pertaining either to the INDs under this CRADA or to the Clinical Investigators on Protocols performed in accordance with the Research Plan, except to the extent that those documents contain the proprietary information of a third party or dissemination is prohibited by law.

 

Add a new Article 3.12 as follows:

 

3.12        Steering Committee and CRADA Research.  The Parties agree to establish a Steering Committee comprising at least the CRADA Principal Investigators to conduct and monitor the proposed and ongoing clinical studies and non-clinical research of the Investigational Agent and Research Agents in accordance with the CRADA Research Plan.  Members of the Steering Committee shall continue to remain employed by their respective employers under their respective terms of employment.

 

The Steering Committee will meet at least once each six months on a mutually-agreeable date and time, and may meet more often as necessary to monitor the ongoing clinical studies and non-clinical research conducted pursuant to the Research Plan.   A meeting of the Steering Committee may be initiated by the Principal Investigator for either party on written notice which will include a proposed agenda for the meeting. The agenda for each meeting will include a report on the status and results to date for each active clinical trial or non-clinical research study.  The Steering Committee will endeavor to make all decisions by consensus.

 

The non clinical and clinical development of Investigational Agent and Research Agents under the CRADA Research Plan shall be a collaborative undertaking by Collaborator and NCI.

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Details of this development beyond those set forth in the CRADA Research Plan shall be formulated and/or discussed in Steering Committee meeting(s) before implementation of large-scale or resource intensive clinical studies.  The clinical development plans formulated by the Steering Committee shall be implemented either intramurally at the NCI or extramurally under NCI-sponsored Funding Agreements.

 

Additional CRADA information, including Steering Committee meeting reports, Protocol Review Committee records, clinical trial protocols, Institutional Review Board approval information, IND and general regulatory information, and non-clinical and clinical data in NCI’s possession and control shall remain on file with NCI and available for review and, as appropriate under this CRADA, for copying by Collaborator.  ICD agrees to provide copies of any CRADA Data reasonably requested by Collaborator to support any Collaborator regulatory filing in any jurisdiction and to provide Collaborator with a right of cross reference to any IND sponsored by DCTD under this CRADA.

 

Add a new Article 3.13 as follows:

 

3.13        Clinical Protocols.  Clinical protocol Letters of Intent (LOI) or concepts for each study within the scope of the CRADA Research Plan will be solicited by CTEP from selected intramural and extramural Clinical Investigators. Clinical protocols from each DCTD- and Collaborator-approved LOI or concept will describe in detail the research to be conducted at each center and must be submitted to the Protocol Review Committee (PRC) for review and approval prior to implementation.  Each clinical protocol received by NCI will be forwarded electronically to Collaborator for review and comment approximately two weeks before it is reviewed by the PRC.  Comments from Collaborator received by CTEP before the PRC meeting will be discussed by the PRC, will be given due consideration, and will be incorporated into the protocol, absent good cause.  Comments from either Collaborator or the CTEP staff that are agreed upon in the PRC meeting will be formatted as a consensus review, which is returned to the Clinical Investigator for necessary and/or suggested changes before the protocol can be given final approval and submitted to the FDA.  A copy of the final approved protocol will be forwarded to Collaborator within 24 to 48 hours of its submission to the FDA.

 

Amend Article 4.2

 

4.2          Final Research and Development Reports. ICD and Collaborator will share CRADA Data as it is developed pursuant to the Research Plan, and will provide final reports of the results of non-clinical studies within [***] of the completion of the study and final reports of the results of clinical trials within [***] of the completion of the trial if available. Collaborator may contract directly with the extramural Clinical Investigator for preparation of a final report if no publication is provided.  The Parties will exchange final reports of their results within [***] after the expiration or termination of this CRADA.  These reports will set forth the technical progress made; any publications arising from the research; and the existence of invention disclosures of potential CRADA Subject Inventions and/or any corresponding

 

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Patent Applications.  Abstracts and publications provided to CTEP by investigators and further provided by CTEP to Collaborator will fulfill this final report obligation. Source documents from clinical studies under this CRADA containing Raw Data in the possession of either Party shall be made available to the other Party upon reasonable request for review and, as appropriate under this CRADA, for copying.

 

Amend Article 4.3

 

4.3          Fiscal Reports.  If Collaborator has agreed to provide funding to ICD under this CRADA and upon the request of Collaborator, ICD will submit to Collaborator a statement of all costs incurred by ICD for the CRADA then concurrent with the exchange of final research and development reports according to Paragraph 4.2.  If the CRADA has been terminated, ICD will specify any costs incurred before the date of termination for which ICD has not received funds from Collaborator, as well as for all reasonable termination costs including the cost of returning Collaborator property or removal of abandoned Collaborator property, for which Collaborator will be responsible.

 

Amend Article 4.4

 

4.4          Safety Reports.  In accordance with FDA requirements, the Sponsor will establish and maintain records and submit safety reports to the FDA, as required by 21 C.F.R. § 312.32 and 21 C.F.R. 812.150(b)(1), or other applicable regulations.  In the conduct of research under this CRADA, the Parties will comply with specific ICD guidelines and policies for reporting ADEs and AEs, as well as procedures specified in the Protocol(s).  The Sponsor must provide the other Party with copies of all Safety Reports concurrently with their submission to the FDA, and with any other information affecting the safety of Human Subjects in research conducted under this CRADA.  DCTD shall report all serious and/or unexpected Adverse Events to FDA in accordance with the reporting obligations of 21 CFR 312.32 and will, within 24 to 48 hours of notification to FDA, forward all such reports to Collaborator.  All other Adverse Event reports received by DCTD shall be reported to the FDA consistent with 21 CFR 312.32 and 312.33.  In the event that Collaborator informs the FDA of any serious and/or unexpected Adverse Events related to clinical trials of the Investigational Agent, Collaborator must notify the NCI at the same time by sending the reports to CTEPSupportAE@tech-res.com.  NCI will then notify the Clinical Investigator(s) conducting studies under DCTD-sponsored protocols, if appropriate.

 

Amend Article 4.5

 

4.5          Annual Reports.  The Sponsor DCTD will provide the other Party Collaborator a copy of the Annual Report concurrently with the submission of the Annual Report to the FDA.  Annual Reports will be kept confidential in accordance with Article 8.  Collaborator will provide DCTD with a copy of its Annual Report to the FDA if Collaborator is sponsoring studies of Investigational Agent under its own IND.

 

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Amend Article 6.1

 

6.1          Ownership of CRADA Subject Inventions, CRADA Data, and CRADA Materials.  Subject to the Government license described in Paragraph 7.5, the sharing requirements of Paragraph 8.1 and the regulatory filing requirements of Paragraph 8.2, the producing Party will retain sole ownership of and title to all CRADA Subject Inventions, all copies of CRADA Data, and all CRADA Materials produced solely by its employee(s).  The Parties will own jointly all CRADA Subject Inventions invented jointly and all CRADA Materials developed jointly.  A PHS contractor’s or grantee’s rights in data it generates will not be affected by this CRADA; provided, however, that ICD will use its reasonable efforts to require each such contractor or grantee to share such data with and permit use of such data by Collaborator in accordance with the terms of this CRADA.

 

Amend Article 6.3

 

6.3          Filing of Patent Applications.  Each Party will make timely decisions regarding the filing of Patent Applications on the CRADA Subject Inventions made solely by its employee(s), and will notify the other Party in advance of filing.  Collaborator will have the first opportunity to file a Patent Application on joint CRADA Subject Inventions and will notify PHS of its decision within sixty (60) days of an Invention being reported or at least thirty (30) days before any patent filing deadline, whichever occurs sooner.  If Collaborator fails to notify PHS of its decision within that time period or notifies PHS of its decision not to file a Patent Application, then PHS has the right to file a Patent Application on the joint CRADA Subject Invention.  Neither Party will be obligated to file a Patent Application; provided, however, that at the written request of Collaborator and at Collaborator’s sole cost and expense, Collaborator may request for ICD to file a Patent Application on any CRADA Subject Invention made solely by ICD employee(s).  Collaborator will place the following statement in any Patent Application it files on a CRADA Subject Invention:  “This invention was created in the performance of a Cooperative Research and Development Agreement with the National Institutes of Health, an Agency of the Department of Health and Human Services.  The Government of the United States has certain rights in this invention.”  If either Party files a Patent Application on a joint CRADA Subject Invention, then the filing Party will include a statement within the Patent Application that clearly identifies the Parties and states that the joint CRADA Subject Invention was made under this CRADA.

 

Amend Article 7.2

 

7.2          Collaborator’s License Option to CRADA Subject Inventions.  With respect to Government rights to any CRADA Subject Invention made solely by an ICD employee(s) or made jointly by an ICD employee(s) and a Collaborator employee(s) for which a Patent Application was filed, PHS hereby grants to Collaborator an exclusive option to elect an exclusive, or co-exclusive, if applicable, or nonexclusive commercialization license.  The option to elect a co-exclusive license shall apply when a CRADA Subject Invention is also a CRADA

 

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Subject Invention under another CRADA resulting from mutually agreed upon studies as described in Article 8.9 and the field of use of this co-exclusive license shall be to the use of the combination of the Investigational Agent with another agent(s) commensurate with the scope of the Research Plan.  The license will be substantially in the form of the appropriate model PHS license agreement and will fairly reflect the nature of the CRADA Subject Invention, the relative contributions of the Parties to the CRADA Subject Invention and the CRADA, a plan for the development and marketing of the CRADA Subject Invention, the risks incurred by Collaborator, and the costs of subsequent research and development needed to bring the CRADA Subject Invention to the marketplace.  The field of use of the license will not exceed the scope of the Research Plan.

 

Amend Article 7.3

 

7.3          Exercise of Collaborator’s License Option.  To exercise the option of Paragraph 7.2 Collaborator must submit a written notice to the PHS Patenting and Licensing Contact identified on the Contacts Information Page (and provide a copy to the ICD Contact for CRADA Notices) within three (3) months after either (i) Collaborator receives written notice from PHS that the Patent Application has been filed or (ii) the date on which Collaborator files the Patent Application.  The written notice exercising this option will include a completed “Application for License to Public Health Service Inventions” and will initiate a negotiation period that expires nine (9) months after the exercise of the option.  If PHS has not responded in writing to the last proposal by Collaborator within this nine (9) month period, the negotiation period will be extended to expire one (1) month after PHS so responds, during which month Collaborator may accept in writing the final license proposal of PHS.  In the absence of Collaborator’s exercise of the option, or upon election of a nonexclusive license, PHS will be free to license the CRADA Subject Invention to others.  These time periods may be extended at the sole discretion of PHS upon good cause shown in writing by Collaborator.

 

Amend Article 7.6

 

7.6          Third Party License.  Pursuant to 15 U.S.C. § 3710a(b)(1)(B), if PHS grants Collaborator an exclusive, or co-exclusive license to a CRADA Subject Invention made solely by an ICD employee or jointly with a Collaborator employee, the Government will retain the right to require Collaborator to grant to a responsible applicant a nonexclusive, partially exclusive, or exclusive sublicense to use the CRADA Subject Invention in Collaborator’s licensed field of use on terms that are reasonable under the circumstances; or, if Collaborator fails to grant a license, to grant a license itself.  The exercise of these rights by the Government will only be in exceptional circumstances and only if the Government determines (i) the action is necessary to meet health or safety needs that are not reasonably satisfied by Collaborator, (ii) the action is necessary to meet requirements for public use specified by federal regulations, and such requirements are not reasonably satisfied by Collaborator; or (iii) Collaborator has failed to comply with an agreement containing provisions described in 15 U.S.C. § 3710a(c)(4)(B).  The determination made by the Government under this Paragraph is subject to administrative appeal

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

and judicial review under 35 U.S.C. § 203(2).

 

Amend Article 8.1

 

8.1          Right of Access to CRADA Data and CRADA Materials.  ICD and Collaborator agree to exchange all CRADA Data and to share all CRADA Materials.  If the CRADA is terminated  pursuant to Sections 10.2 or 10.3, both Parties agree to provide CRADA Materials in quantities needed to complete the Research Plan; provided, however, that either Party’s obligation shall be limited to supplying quantities of CRADA Materials sufficient to complete activities under the Research Plan for the first [***] following termination of the CRADA.  Such provision will occur before the termination date of the CRADA or sooner, if required by the Research Plan.  If Collaborator possesses any human biological specimens from clinical trials under the CRADA, the specimens must be handled as described in the Protocol or as otherwise directed by ICD before the termination date of the CRADA.

 

Amend Article 8.2

 

8.2          Use of CRADA Data and CRADA Materials.  The Parties will be free to utilize CRADA Data and CRADA Materials internally for their own purposes, consistent with their obligations under this CRADA.  ICD may share CRADA Data or CRADA Materials with any contractors, grantees, or agents it has engaged to conduct the CRADA research and development activities, provided the obligations of this Article 8.2 are simultaneously conveyed. Collaborator may use CRADA Data, Raw Data, and CRADA Materials for the research, development and commercialization of products and may share CRADA Data, Raw Data or CRADA Materials with its Affiliates and development partners and with any contractors Affiliates, or agents it has engaged to conduct the CRADA research and development activities, provided the obligations of this Article 8.2 are simultaneously conveyed.

 

Amend Article 8.6

 

8.6          Duration of Confidentiality Obligation.  The obligation to maintain the confidentiality of Confidential Information will expire at the earlier of the date when the information is no longer Confidential Information as defined in Paragraph 2.4 Article 2 or three (3) years after the expiration or termination date of this CRADA, except for IPI, for which the obligation to maintain confidentiality will extend indefinitely, and manufacturing know how and information related to poxvirus-based cancer vaccine process development for which the obligation to maintain confidentiality shall extend until such information is no longer Confidential Information.  Collaborator may request an extension to this term when necessary to protect Confidential Information relating to products not yet commercialized.

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Amend Article 8.7

 

8.7          Publication.  The Parties are encouraged to make publicly available the results of their research and development activities.  Before either Party Collaborator or NCI CCR investigator(s) submits a paper or abstract for publication or otherwise intends to publicly disclose information about a CRADA Subject Invention, CRADA Data, or CRADA Materials, the other Party will have thirty (30) days to review proposed manuscripts and three (3) business  days to review proposed abstracts to assure that Confidential Information is protected.  Either Party may request in writing that the a proposed publication or other disclosure be delayed for up to thirty (30) additional days as necessary to file a Patent Application.  Manuscripts to be submitted for publication by NCI non-CCR investigators will be sent to NCI’s Regulatory Affairs Branch [***] for forwarding to Collaborator for review as soon as they are received and in compliance with the timelines outlined above, to allow for preservation of U.S. or foreign patent rights. In addition, NCI non-CCR investigators will provide all manuscripts and abstracts to NCI’s Regulatory Affairs Branch [***] at the same time they provide them to Collaborator. Abstracts to be presented by NCI investigators will be sent to NCI’s Regulatory Affairs Branch [***] for forwarding to Collaborator as soon as they are received, preferably no less than [***].

 

Amend Article 8.8

 

8.8          Clinical Investigators’ Research and Development Activities.  In pursuing the development of  Investigational Agent and Research Agents pursuant to this CRADA, NCI may utilize contractors and extramural investigators that are not NCI employees for part or all of the completion of this Research Plan, which may cover non-clinical and clinical studies.  Participation in DCTD-sponsored clinical trials by these investigators shall be determined after competitive solicitation and review of Protocol Letters of Intent (LOIs) and study protocols by CTEP, NCI.  All Funding Agreements, for the conduct of extramural clinical trials will include CTEP’s Intellectual Property Option to Collaborator, Terms of Award Addition, offering Collaborator first rights of negotiation to extramural inventions (web site: http://ctep.cancer.gov/industry).  Although this CRADA does not grant to Collaborator any rights to Inventions made or Raw Data generated by ICD’s NCI’s contractors or grantees, as they are not parties to this CRADA, ICD NCI agrees that:

 

8.8.1       Subject to the other provisions of Article 8 of this CRADA, ICD NCI will maintain, to the extent permitted by law, all Clinical Data in ICD’s NCI’s Possession and Control as Confidential Information, and make them available to Collaborator for its own use and for exclusive use in obtaining regulatory approval for the commercial marketing of Test Article Investigational Agent and related CRADA Subject Inventions.  Similarly, NCI will also maintain, to the extent permitted by law, all data generated in non-clinical studies that are in NCI’s possession and control as Confidential Information in accordance with Article 8.2.1, and make them available to Collaborator for its own use and for use in obtaining regulatory approval for the commercial marketing of  Test

 

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***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Articles and related CRADA Subject Inventions.  Collaborator will not publish any such data provided under the CRADA without NCI’s permission.  Accordingly, said data shall not be transferable by Collaborator to any third party, except to Collaborator Affiliates and development partners, without the written permission of the NCI. Following NCI’s permission, the third party shall enter into a Confidential Disclosure Agreement with the NCI and Collaborator, if requested by NCI, before any data can be transferred. The Parties agree that the forgoing restrictions on publication do not apply to data submitted in connection with any regulatory filing by Collaborator.

 

8.8.2       With regard to Collaborator’s or its Affiliate(s)’ Confidential Information, ICD NCI will require the Clinical Investigators to agree to confidentiality provisions at least as restrictive as those provided in this CRADA and to Collaborator’s use of data in accordance with Paragraph 8.8.1 for obtaining regulatory approval for marketing Test Articles.

 

8.8.3 If Collaborator wants access to Raw Data or any other data in the possession of the Clinical Investigators working with Test Article Investigational Agent under a Funding Agreement or other agreements, Collaborator must first contact the CRADA PI [***].  Subsequent to authorization by RAB, Collaborator may directly contact the Clinical Investigators.  Collaborator will bear any costs associated with Raw Data provided in formats customized for Collaborator, which costs will be paid by Collaborator directly to the Clinical Investigators.

 

8.8.4 Collaborator’s right to access Clinical Data in ICD’s NCI’s Possession and Control under Paragraph 8.8 is dependent upon Collaborator’s continued development and commercialization of Investigational Agent.  If Collaborator fails to continue development or commercialization of Investigational Agent without the transfer of its development efforts to another party within ninety (90) days of discontinuation, ICD NCI has the right to make Clinical Data in ICD’s NCI’s Possession and Control available to a third party.

 

Add a new Article 8.9 as follows:

 

8.9          Multi-Party Data Rights. For clinical protocol(s) where Investigational Agent is used in combination with another investigational agent supplied to NCI pursuant to a CTA or CRADA between NCI and an entity not a Party to this CRADA [hereinafter referred to as “Third Party”], the access and use of Multi-Party Data by the Collaborator and Third Party shall be co-exclusive as follows:

 

8.9.1       NCI will provide both Collaborator and Third Party with notice regarding the existence and nature of the agreements governing their collaborations with NIH, the

 

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design of the proposed combination protocol(s), and the existence of any obligations that might restrict NCI’s participation in the proposed combination protocols.

 

8.9.2       Collaborator shall agree to permit use of the Multi-Party Data from these trials by Third Party to the extent necessary to allow Third Party to develop, obtain regulatory approval for, or commercialize its own investigational agent(s).  However, this provision will not apply unless Third Party also agrees to Collaborator’s reciprocal use of Multi-Party Data.

 

8.9.3       Collaborator and Third Party must agree in writing prior to the commencement of the combination trial(s) that each will use the Multi-Party Data solely for the development, regulatory approval, and commercialization of its own investigational agent(s).

 

Add a new Article 8.10 as follows:

 

8.10        Access, review and receipt of Identifiable Private Information. Collaborator access to and review of Identifiable Private Information shall be only for on-site quality auditing. Collaborator will receive Identifiable Private Information only if necessary for purposes of satisfying FDA or other health authorities’ reporting requirements, and for internal research purposes, directly related to obtaining regulatory approval of Investigational Agent.  Collaborator is prohibited from access, review, receipt, or use of such information for other purposes.  All IRB approved protocols and informed consent documents related to this research project will clearly describe this practice.  If the Collaborator will have access to Identifiable Private Information, the protocol and the informed consent must clearly state (i) the existence of the Collaborator; (ii) the Collaborator’s access to Identifiable Private Information, if any; and (iii) the extent to which confidentiality will be maintained.  For clinical protocol(s) involving a third party, the other party’s access, review, receipt, or use of Identifiable Private Information shall be subject to the same limitations as described in this Article 8.10.

 

Amend Article 9.1.2

 

9.1.2                     To the best of its knowledge and belief, neither ICD nor any of its personnel involved in this CRADA is presently subject to debarment or suspension by any agency of the Government which would directly affect its performance of the CRADA.  Should ICD or receive notice that any of its personnel or Clinical Investigators, contractors or grantees involved in this CRADA may be debarred or suspended during the term of this CRADA, ICD will notify Collaborator within thirty (30) days of receipt of such final notice.

 

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Amend Article 9.2.2

 

9.2.2                     To the best of its knowledge and belief, Nneither Collaborator nor any of its personnel involved in this CRADA, including Affiliates, agents, and contractors are presently subject to debarment or suspension by any agency of the Government.  Should Collaborator receive notice that it or any of its personnel involved in this CRADA may be debarred or suspended during the term of this CRADA, Collaborator will notify ICD within thirty (30) days of receipt of such notice.

 

9.2.4                     The Test Article Investigational Agent provided has been produced in accordance with the FDA’s current Good Manufacturing Practice set out in 21 C.F.R. §§ 210-211, and ICH QA7, and meets the specifications cited in the Certificate of Analysis and the information supplied by Collaborator for the Investigator’s Brochure provided.

 

Amend Article 10.3

 

10.3                        Unilateral Termination.  Either ICD or Collaborator may unilaterally terminate this CRADA at any time by providing written notice at least sixty (60) days before the desired termination date.  ICD may, at its option, retain funds transferred to ICD before unilateral termination by Collaborator for use in completing the Research Plan.  If Collaborator terminates this Agreement before the completion of all approved or active Protocol(s), then Collaborator will supply enough Test Article (and Placebo, if applicable) to complete these Protocol(s) unless termination is for safety concerns.  In the event of termination of the CRADA prior to the expiration date, or upon expiration of the CRADA, Collaborator will continue to provide cross reference letters to its DMFs and/or INDs in order to enable ICD to complete the studies approved, initiated or active.

 

Amend Article 10.6

 

10.6        Collaborator Failure to Continue Development.  If Collaborator suspends development of the Test Article Investigational Agent without the transfer of its active development efforts, assets, and obligations to a third party within ninety (90) days of discontinuation, Collaborator agrees that ICD may continue developing the Test Article Investigational Agent.  In that event, the following will apply:

 

10.6.1     Collaborator agrees to transfer to ICD all information necessary to enable ICD to contract for the manufacture of the Test Article Investigational Agent and, unless abandoned for reasons relating to safety as determined by the data safety monitoring board, to provide the Test Article Investigational Agent (and Placebo, if any) in Collaborator’s inventory to ICD  In addition, Collaborator will cause to be manufactured or arrange for an independent contractor to manufacture and provide Investigational

 

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Agent to NCI in sufficient quantity to complete (i) the preclinical and clinical studies of Investigational Agent then planned or (ii) for the preclinical and clinical studies then planned for the two years following such discontinuation, whichever is lesser.

 

10.6.2     Further, Collaborator hereby grants to ICD a nonexclusive, irrevocable, world-wide, paid-up license to practice, or have practiced for or on behalf of the Government, any Background Invention that Collaborator may currently have or will obtain on the Test Article Investigational Agent, its manufacture, or on any method of using the Test Article Investigational Agent for the indication(s) described in the Research Plan, including the right to sublicense to third parties

 

Amend Article 12.2

 

12.2        Indemnification and Liability.  Collaborator agrees to hold the Government harmless and to indemnify the Government for all liabilities, demands, damages, expenses and losses arising out of the use by Collaborator for any purpose of the CRADA Data, CRADA Materials or CRADA Subject Inventions produced in whole or part by ICD employees under this CRADA, unless due to breach of this Agreement or the negligence or willful misconduct of ICD, its employees, or agents.  The Government has no statutory authority to indemnify Collaborator.  Each Party otherwise will be liable for any claims or damages it incurs in connection with this CRADA, except that ICD, as an agency of the Government, assumes liability only to the extent provided under the Federal Tort Claims Act , 28 U.S.C. Chapter 171.

 

Amend Article 13.9

 

13.9        Independent Contractors.  The relationship of the Parties to this CRADA is that of independent contractors and not agents of each other or joint venturers or partners.  Each Party will maintain sole and exclusive control over its personnel and operations.  If Collaborator elects to perform any portion of the Research Plan through a contractor or consultant, Collaborator agrees to incorporate into such contract all provisions necessary to ensure that the work of such contractor or consultants is governed by the terms of the CRADA, including, but not limited to a provision for the assignment of inventions of the contractor or consultant to the Collaborator.

 

Amend Article 13.10

 

13.10      Use of Name; Press Releases.  By entering into this CRADA, the Government does not directly or indirectly endorse any product or service that is or will be provided, whether directly or indirectly related to either this CRADA or to any patent or other intellectual-property license or agreement that implements this CRADA by Collaborator, its successors, assignees, or licensees.  Collaborator will not in any way state or imply that the Government or any of its organizational units or employees endorses any product or services.  Each Party agrees to provide proposed press releases that reference or rely upon the work under this CRADA to the other Party for review and comment at least five (5) business days before publication or such

 

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shorter period as may be required by law or the rules of any securities exchange.  Either Party may disclose the Title and Abstract of the CRADA to the public without the approval of the other Party.

 

Amend Article 13.12

 

13.12      Export Controls.  Collaborator agrees to comply with U.S. export law and regulations, including 21 U.S.C. 382 and 21 CFR Part 312.110.  If Collaborator has a need to transfer any CRADA Materials made in whole or in part by ICD, or ICD Materials, or ICD’s Confidential Information to a person located in a country other than the United States, to an Affiliate organized under the laws of a country other than the United States, or to an employee of Collaborator in the United States who is not a citizen or permanent resident of the United States, Collaborator will acquire any and all necessary export licenses and other appropriate authorizations.

 

Amend Article 13.14

 

13.14      Survivability.  The provisions of Paragraphs 3.3, 3.4, 3.8, 4.2, 4.3, 4.4, 5.3, 5.4, 6.1-9.2, 10.3-10.6, 11.1, 11.2, 12.1-12.3, 13.1-13.3, 13.7, 13.10 and 13.14 will survive the expiration or early termination of this CRADA.

 

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CONFIDENTIAL
    	
 
    	
NCI — BN   ImmunoTherapeutics
    
	
 
    	
 
    	
Amendment #1 to CRADA   #02377
    

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

Amendment #1 to
 Cooperative Research and Development Agreement #02377

 

“The Development of Recombinant Poxviruses As Vaccine
 Immunotherapies for the Treatment and/or Prevention of Human
 Prostate Cancer”

 

The purpose of this amendment is to change certain terms of the above-referenced Cooperative Research and Development Agreement (CRADA). These changes are reflected below, and except for these changes, all other provisions of the original CRADA remain in full force and effect.

 

The Parties agree as follows:

 

1.  The term of the CRADA is extended for five (5) years from August 12, 2013 to August 12, 2018.

 

2.  Article 7.8 is deleted in its entirety.

 

3.  The name of the Collaborator Principal Investigator is changed to James Breitmeyer, M.D., Ph.D.

 

4.  Article 10.5 is modified to read as follows where strikeout indicates deletions and underline indicates additions:

 

10.5        New Commitments.  Neither Party will incur new expenses related to this CRADA after expiration, mutual termination, or a notice of a unilateral termination and will, to the extent feasible, cancel all outstanding commitments and contracts by the termination date. Collaborator acknowledges that IC will have the authority to retain and expend any funds for up to [***] subsequent to the expiration or termination date to cover any unpaid costs obligated during the term of the CRADA in undertaking the research and development activities set forth in the Research Plan and for ongoing CRADA-related expenses that arise after the expiration or termination date, such as vaccine stability testing, managing or analyzing CRADA Data and CRADA Materials, continuing ongoing clinical trials, and conducting follow-up observations of Human Subjects treated under the CRADA, such that the authority to make these expenditures will survive the CRADA.

 

1

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

ACCEPTED AND AGREED TO:

 

	
For the National Cancer   Institute
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
[***]
    	
 
    	
6/25/13
    
	
[***]
    	
 
    	
Date
    
	
 
    	
 
    	
 
    
	
Deputy Director for   Clinical and Translational
    	
 
    	
 
    
	
Research, NCI
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
For Collaborator:
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
[***]
    	
 
    	
28 May 2013
    
	
Name:
    	
[***]
    	
 
    	
Date
    
	
Title:
    	
President, BN   Immunotherapeutics, Inc.
    	
 
    	
 
    

 

2

 

Amendment #2 to
 Cooperative Research and Development Agreement #02377

 

“The Development of Recombinant Poxviruses As Vaccine Immunotherapies 
 for the Treatment and/or Prevention of Human Prostate Cancer”

 

The purpose of this amendment is to change certain terms of the above-referenced Cooperative Research and Development Agreement (CRADA).  These changes are reflected below, and except for these changes, all other provisions of the original CRADA, as amended by Amendment #1 on June 21, 2013, remain in full force and effect.

 

The Parties agree as follows:

 

1.  Article 8.2 is modified to read as follows where underline indicates additions:

 

8.2                               Use of CRADA Data and CRADA Materials.  The Parties will be free to utilize CRADA Data and CRADA Materials internally for their own purposes, consistent with their obligations under this CRADA.  ICD may share CRADA Data or CRADA Materials with any contractors, grantees, or agents it has engaged to conduct the CRADA research and development activities, provided the obligations of this Article 8.2 are simultaneously conveyed.  Collaborator may use CRADA Data, Raw Data, and CRADA Materials for the research, development and commercialization of products and may share CRADA Data, Raw Data or CRADA Materials with its Affiliates and development partners and with any contractors or agents it has engaged to conduct the CRADA research and development activities, provided the obligations of this Article 8.2 are simultaneously conveyed.  Consistent with the obligations in this CRADA, including Articles 8.5 and 8.10, Collaborator shall have the exclusive right to use CRADA Data, Raw Data, and CRADA Materials for the commercial development (including in all regulatory filings seeking marketing approval for a new indication (e.g., NDAs and sNDAs)) and commercialization of therapies for prostatic diseases pursuant to the Licensed Field of Use under, and to conduct the activities permitted by, the PHS Exclusive Patent License Agreement #L-149- 2008/0 and amended in a first amendment #L-149-2008/1 and a second amendment #L-149-2008/2.  For the avoidance of doubt, “commercial development” refers to all the pre-marketing approval activities needed to commercialize a product, and any IND filings made by ICD will be considered for research purposes and not commercial development. “Commercialization” refers to all the post-marketing approval activities connected with launching, marketing, promoting, advertising, selling and/or distributing a product.

 

2.  At1icle 8.2.1 is modified to read as follows where underline indicates additions:

 

8.2.1                     CRADA Data.  Collaborator and ICD will use reasonable efforts to keep CRADA Data and Raw Data confidential until published or until corresponding Patent Applications are filed.  To the extent permitted by law, either Party will

 

1

 

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(2), (4), (5) and (6) and 230.406

 

have the right to use any and all CRADA Data and Raw Data in and for any regulatory filing by or on behalf of the Patty. provided. however. That Collaborator shall have the exclusive right to use CRADA Data and Raw Data in regulatory filings for approvals and other commercial purposes for PSA-Tricom (Prostvac®).

 

3.  Article 10.3 is modified to read as follows where underline indicates additions:

 

10.3                        Unilateral Termination.  Either ICD or Collaborator may unilaterally terminate this CRADA at any time by providing written notice at least sixty (60) days before the desired termination date.  ICD shall provide a copy of any such notice to any third party previously designated in writing by Collaborator to receive such notices at the same time as ICD provides such notice to Collaborator.  ICD may, at its option, retain funds transferred to ICD before unilateral termination by Collaborator for use in completing the Research Plan.  If Collaborator terminates this Agreement before completion of all approved or active Protocol(s), then Collaborator will supply enough Test Article (and Placebo, if applicable) to complete these Protocol(s) unless termination is for safety concerns.  In the event of termination of the CRADA prior to the expiration date, or upon expiration of the CRADA, Collaborator will continue to provide cross reference letters to its DMFs and/or INDs in order to enable ICD to complete the studies approved, initiated or active.

 

ACCEPTED AND AGREED TO:

 

For the National Cancer Institute

 

 

	
[***]
    	
 
    	
4/25/2015
    
	
[***]
    	
 
    	
Date
    
	
 
    	
 
    	
 
    
	
Deputy Director for   Clinical and
    	
 
    	
 
    
	
Translational Research,   NCI
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
For Collaborator:
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
[***]
    	
 
    	
17 APR 2015
    
	
Name:
    	
[***]
    	
 
    	
Date
    
	
Title:
    	
President, Bavarian   Nordic, Inc.
    	
 
    	
 
    

 

2

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