Exhibit 10.1

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

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” or “Agreement”) 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

NIDDK

an Institute or Center

(hereinafter referred to as the “IC”) of the

NIH

and

Raptor Therapeutics, Inc.,

(hereinafter referred to as the “Collaborator)

having offices at 9 Commercial Blvd., Suite 200

Novato, CA 94949,

created and operating under the laws of Delaware.

¨ COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

FOR EXTRAMURAL-PHS CLINICAL RESEARCH

 

Article 1. Introduction

This CRADA between IC 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 IC, IC’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.

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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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).

“Background Invention” means an Invention conceived and first actually reduced
to practice (a) before the Effective Date or (b) outside of the activities under
the Research Plan.

“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.

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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

“Clinical Trial” means the clinical trial to be performed in accordance with the
Protocol under this CRADA.

“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 all information of a confidential or
proprietary nature (including scientific, business, financial information, or
Identifiable Private Information) of one Party provided to another Party under
this CRADA; provided that Confidential Information does not include:

 

  (a)

information that is publicly known or that is available from public sources;
except by acts or omissions of the receiving Party in breach of this CRADA;

 

  (b)

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

 

  (c)

information that is already known by the receiving Party other than under an
obligation of confidentiality, or information that is independently created or
compiled by the receiving Party without reference to or use of the Confidential
Information of the disclosing Party.

“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 all information developed by or on behalf of a Party in the
performance of the Research Plan, including Summary Data, but excluding Raw
Data. “CRADA Collaborator Principal Investigator(s)” or “CRADA Collaborator
PI(s)” means the person(s) who will be responsible for the scientific and
technical conduct of the Research Plan on behalf of the CRADA Collaborator.

“CRADA Subject Invention” means any Invention conceived or first actually
reduced to practice by a Party in the performance of the Research Plan. For
clarity, Inventions directed to the Test Article, or its manufacture or use,
which are conceived or first actually reduced to practice by or on behalf of
Collaborator in the course of activities outside the Research Plan (including
without limitation manufacture of Test Article provided by Collaborator
hereunder) shall not be deemed to be “in the performance of the Research Plan”
solely by virtue of Collaborator’s supply of the Test Article under this CRADA.

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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

“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.

“IC Materials” means all tangible materials not first produced in the
performance of this CRADA that are owned or controlled by IC 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.

“Invention” means any invention or discovery that is or may be patentable or
otherwise protected under Title 35 of the United States Code by the U.S. Patent
and Trademark Office or the corresponding patent-issuing authority of another
nation, 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. by the U.S. Patent and
Trademark Office or the corresponding patent-issuing authority of another
nation.

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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

“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.

“NIH CRADA Extramural Investigator/Officer(s)” means the Extramural staff who
are responsible for the conduct and/or management of the CRADA on behalf of the
IC.

“Patent Application” means an application for patent protection, any
continuations, continuations-in-part, substitutions or divisional applications
thereof, 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 United States patent that issues on a Patent Application and
any international counterpart(s) thereof, and any other patents issued by the
U.S. Patent and Trademark Office or the corresponding patent-issuing authority
of another nation on a Patent Application and any corresponding grant(s) by the
corresponding patent-issuing authority of another nation. For clarity, “Patent”
includes renewals, reissues, re-examinations, extensions and the like of all of
the foregoing.

“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 the study to be performed
as summarized in the Research Plan and approved by the Parties as further set
forth hereunder. It describes the objective(s), design, methodology, statistical
considerations, and organization of a trial. The most recent version of the
Protocol is incorporated by reference into this Agreement. 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. Any
changes to the Protocol that are material to the design of the study being
conducted under this CRADA or the use or administration of the Test Article will
require prior written approval by Collaborator (except for reasons of patient
safety pursuant to Paragraph 3.6 below); and Collaborator shall use commercially
reasonable efforts to act on any such request for approval within one (1) week
of its receipt of such request. In the event of a conflict between the CRADA
Research Plan and the Protocol, the Protocol shall control.

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

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

“Research Plan” means the statement in Appendix A of the respective research and
development commitments of the Parties and approved by the Parties. The Research
Plan should describe the provisions for sponsoring the IND, clinical and safety
monitoring, and data management. For clarity, the manufacture of the Test
Article is outside the scope of the Research Plan.

“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 and development performed under
this CRADA are described in Appendix A.

“Summary Data” means any extract or summary of the Raw Data, generated either by
or on behalf of IC, or by or on behalf of Collaborator, including all data
collected pursuant to the “Data Collection Schedule” as set forth in the
Protocol and the compiled and analyzed data sets containing such data.

“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. The Test Article to be used in this CRADA is Cysteamine Delayed Release
(DR) tablet (internally referred to by Collaborator as “RP104”).

 

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 IC’s contractors or grantees as described in the
Research Plan (including the Clinical Research Sites and Clinical
Investigators), in accordance with the terms and conditions of this CRADA and
all applicable laws, rules and regulations. Notwithstanding that IC’s
contractors or grantees are not Parties to the CRADA, and this CRADA does not
grant to Collaborator any rights to Inventions made by IC’s contractors or
grantees, IC agrees that its contractors and grantees (including the Clinical
Research Sites and Clinical Investigators) will be required to comply with the
Research Plan and Protocol; will use the Test Article, Placebo and Collaborator
Materials in accordance with the Protocol and the terms and conditions under
Paragraph 3.10 below, and will make available or otherwise provide access to all
CRADA Data in accordance with Article 8 below. IC further agrees to notify
Collaborator promptly upon becoming aware of any noncompliance with the
foregoing and to discuss in good faith any action to be taken against its
contractors and grantees in response to such noncompliance, including seeking
any available remedies under any applicable law or in equity. The NIH CRADA
Extramural Investigator/Officer(s) and CRADA Collaborator PI(s) 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 IC 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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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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 IC Materials. IC agrees to
use, and will require the Clinical Investigators to use, Collaborator Materials,
and Collaborator agrees to use IC Materials, only in accordance with the
Research Plan and Protocol. Each Party agrees not to transfer materials provided
by the other Party to third parties except in accordance with the Research Plan
and Protocol or as approved by the providing Party (i.e. approval by
Collaborator in the case of Collaborator Materials, and approval by IC in the
case of IC Materials), 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 directly
and specifically in exchange for rights in any of Collaborator’s CRADA Subject
Inventions, Collaborator agrees to use reasonable efforts to ensure that its
obligations to the third party are both consistent with Articles 6 through 8 and
subordinate to those provisions of Article 7 of this CRADA applicable to
Collaborator’s CRADA Subject Inventions; provided, however, that Collaborator
shall have no obligation to renegotiate or amend its existing agreements with
third parties.

 

3.5

Disclosures to IC. Prior to execution of this CRADA, Collaborator agrees to
disclose to IC 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 the
definition in Article 2 and Paragraphs 8.3 and 8.4.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

3.6

Clinical Investigator Responsibilities. The Clinical Investigator will be
required to submit, or to arrange for submission of, each Protocol and
advertisement associated with this CRADA to all appropriate IRB(s), and for
ensuring that the IRB(s) are notified of the role of the Collaborator in the
research. In addition to the Protocol, all associated documents, including
informational documents, must be reviewed and approved by both Parties and the
appropriate IRB(s) before starting the research at each Clinical Research Site.
The research and development 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 IRB(s). In the event
that the IRB or the Data Safety Monitoring Committee recommend changes to the
Protocol for reasons of patient safety, those changes may be made immediately
provided that the IC or Clinical Investigator promptly notify Collaborator of
the intent and need to make such changes and allow Collaborator to comment if
reasonably practical. Notwithstanding the foregoing, Collaborator shall be
informed promptly of any changes incorporated by the IRB or Data Safety
Monitoring Committee and shall be permitted to provide suggestions and comments.

 

3.7

Investigational Applications.

3.7.1 If an IND is required to perform the research and development activities
under this CRADA, then the IC will submit an IND and ensure all Clinical
Investigators have completed all necessary registration documents (1572 forms).

3.7.2 If IC files its own IND pursuant to Paragraph 3.7.1 above, then
Collaborator agrees to provide IC any background data and information under its
control 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 IC by the Collaborator pursuant to this Article 3. If Collaborator files its
own IND filings pursuant to Paragraph 3.7.4 below, then IC agrees to provide
Collaborator any background data and information under its control necessary to
support the IND and to provide a letter of cross reference to its IND and
respond to inquiries related to information provided by IC, as applicable.

3.7.3 If Collaborator supplies Confidential Information to IC in support of an
IND filed by IC, 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 during the term of the CRADA, 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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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

3.8

Test Article Information and Supply. Collaborator agrees to use reasonable
efforts to provide IC, or its designee as agreed, and on a schedule that will
ensure adequate and timely performance of the Research Plan 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 without charge to IC or its designee.
Collaborator and IC will agree upon a drug supply schedule which will ensure
adequate and timely performance of the Research Plan, prior to commencement of
the treatment of the first Human Subject. Collaborator will provide a
Certificate of Analysis to IC for each lot of the Test Article provided.

 

3.9

Test Article Delivery and Usage. Collaborator will ship the Test Article to IC
or its designee in containers marked in accordance with 21 C.F.R. § 312.6. IC
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 and applicable FDA regulations, and shall ensure that any contractor or
grantee or Clinical Research Site performing research and development activities
under this CRADA shall only use the Test Article in accordance with the Protocol
and applicable FDA regulations. In addition, IC 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, IC 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 IC or its designee will be determined by IC
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, IC will obtain
or has obtained permission from the Clinical Research Sites for the Collaborator
or its designee(s) to access the Clinical Research Sites 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); provided Collaborator and IC agree in advance to 1) reasonable
advance notice 2) reasonable monitoring times, and 3) reasonable reimbursement
by Collaborator to Clinical Research Sites for the time and materials required
to provide the personnel and documents that will be required for the audit.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

3.10.3 In the performance of the CRADA, IC will, and the Clinical Investigators
are obligated to, use reasonable efforts to accurately and efficiently perform
the Research Plan as agreed between the Parties under this Agreement. This shall
include, without limitation:

 

  (i)

exercising independent medical judgment as to the compatibility of each Human
Subject with the Protocol requirements;

 

  (ii)

notifying Collaborator and IRB in writing in no event later than the time
periods specified by the applicable regulations, of any Adverse Drug Experience
or Adverse Event which occur during the performance of the CRADA;

 

  (iii)

notifying Collaborator and IRB promptly in writing of any deviations from the
Protocol and the dates of and reasons for any deviations from the Protocol;
provided that prior written approval by Collaborator is required for any
deviations from the Protocol except for reasons of patient safety as set forth
under Paragraph 3.6 above;

 

  (iv)

notifying Collaborator in writing of the withdrawal of IRB approval of any part
of the Protocol including any Clinical Investigator’s participation in the
conduct of the Protocol promptly, and in any event within five (5) days,
following receipt of notice from the IRB of such withdrawal of approval; and

 

  (v)

notifying Collaborator and IRB in writing promptly of any failure to obtain
informed consent from any Human Subject prior to use of the Test Article in
connection with such Human Subject, and in any event within five (5) days, after
discovery of such use.

 

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 IC in advance. Each Party reserves the right to take part in setting the
agenda for, to attend, and to participate in these meetings and IC agrees not to
object to Collaborator’s attendance at any meetings with the FDA with an
established agenda directed to and within the scope of the Research Plan. IC
agrees to provide Collaborator with copies of FDA meeting minutes after such
meetings, regardless of whether Collaborator attends, as well as copies of all
transmittal letters for IND submissions, IND safety reports, formal questions
and responses that will be 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 a reasonable time period prior to submittal to the FDA to allow
Collaborator to review prior to submittal, when practicable, except to the
extent that those documents contain the proprietary information of a third party
or dissemination is prohibited by law. IC will consider Collaborator’s comments
with regard to any response or letters sent to the FDA prior to their submittal.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

Article 4. Reports

 

4.1

Interim Research and Development Reports. The NIH CRADA Extramural
Investigator/Officer(s) and CRADA Collaborator PI(s) 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 IC under this
CRADA and upon the request of Collaborator, then each calendar year and
concurrent with the exchange of final research and development reports according
to Paragraph 4.2, IC will submit to Collaborator a statement of all costs
incurred by IC for the CRADA. If the CRADA has been terminated, IC will specify
any costs incurred before the date of termination for which IC 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 IC 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 IC
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.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

Article 5. Staffing, Financial, and Materials Obligations

 

5.1

IC 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 IC from
providing funds to Collaborator for any research and development activities
under this CRADA.

 

5.2

IC Staffing. No IC employees will devote 100% of their effort or time to the
research and development activities under this CRADA. IC will not use funds
provided by Collaborator under this CRADA for IC personnel to pay the salary of
any permanent IC employee. Although personnel hired by IC 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 IC under this CRADA. If Collaborator has agreed to
provide funds to IC 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, IC 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. IC will use these
funds exclusively for the purposes of this CRADA and upon notice of any event
that will cause significant delay in the conduct of the Research Plan, IC shall
use reasonable efforts to delay the further commitment of any funds provided to
or to be provided to IC by Collaborator in accordance with Appendix B. 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 IC with capital
equipment to enable the research and development activities under the Research
Plan appears in Appendix B. If Collaborator transfers to IC the capital
equipment or provides funds for IC to purchase it, then IC will own the
equipment. If Collaborator loans capital equipment to IC 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 IC will not be liable for any damage to the equipment.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

Article 6. Intellectual Property

 

6.1

Ownership of CRADA Subject Inventions and CRADA Data. Subject to the Government
license described in Paragraph 7.5, the sharing requirements of Paragraph 8.1
and the regulatory filing requirements and other provisions of Paragraph 8.2,
the producing Party will retain sole ownership of and title to all CRADA Subject
Inventions and all copies of CRADA Data produced solely by its employee(s). The
Parties will own jointly all CRADA Subject Inventions invented jointly. An IC
contractor’s or grantee’s rights in data and materials it generates will not be
affected by this CRADA, except as otherwise provided to IC in accordance with
its funding agreement with IC as a contractor or grantee to conduct the Research
Plan.

 

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. 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 NIH 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
NIH of its decision within that time period or notifies NIH of its decision not
to file a Patent Application, then NIH has the right to file a Patent
Application on the joint CRADA Subject Invention, and if NIH files a Patent
Application, Collaborator will be notified and the Parties will cooperate with
each other concerning any claims on which Collaborator’s employee is an inventor
or co-inventor. 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 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.

 

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
an exclusive 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
for such Patent Applications and Patents claiming exclusively licensed CRADA
Subject Inventions. If a nonexclusive license to any CRADA Subject Invention is
granted to Collaborator, then Collaborator 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).

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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 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 NIH a power(s) of attorney (or equivalent)
necessary to assure NIH access to its intellectual property rights in these
Patent Applications. NIH 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. 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. NIH hereby grants to
Collaborator a non-exclusive, royalty-free, perpetual, irrevocable,
transferable, worldwide internal research use license with respect to any NIH
sole CRADA Subject Invention for which a Patent Application was filed. With
respect to Government rights to any CRADA Subject Invention made solely by an IC
employee(s) or made jointly by IC employee(s) and a Collaborator employee(s) for
which a Patent Application was filed NIH hereby grants to Collaborator an
exclusive option to elect an exclusive worldwide license to make, have made,
use, offer for sale, sell, import and otherwise exploit such CRADA Subject
Invention. Such exclusive 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. Such exclusive license will also be granted with a
defined field of use not to exceed the scope of the Research Plan, provided that
the Parties shall amend the Research Plan from time-to-time to reflect any
additional research and development activities performed in connection with this
CRADA that are not reflected in the then-current Research Plan. Such exclusive
license, to be negotiated by NIH and Collaborator, will also include the right
to grant and authorize sublicenses subject to certain limitations.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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
IC Contact for CRADA Notices) within [*****] In the absence of Collaborator’s
exercise of the option, NIH will be free to license the CRADA Subject Invention
to others. The foregoing time periods for the option and negotiation of an
exclusive license above may be extended at the sole discretion of NIH upon good
cause shown in writing by Collaborator and NIH shall not negotiate with, or
grant any rights to, a third party with respect to such CRADA Subject Inventions
during such time periods.

 

7.4

Government License in IC Sole CRADA Subject Inventions and Joint CRADA Subject
Inventions. Pursuant to 15 U.S.C. § 3710a(b)(1)(A), for CRADA Subject Inventions
owned solely by IC or jointly by IC and Collaborator, and licensed pursuant to
the option of Paragraph 7.2, Collaborator grants to the Government 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. 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.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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
IC 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(b).

 

7.7

Third-Party Rights In IC Sole CRADA Subject Inventions. For a CRADA Subject
Invention conceived prior to the Effective Date solely by an IC 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
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 without obligation of accounting to the other Party for such use or
activities. 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 Human Biological Specimens. [*****]

 

8.2

Use of CRADA Data. [*****]

 

  8.2.1

CRADA Data. [*****]

 

8.3

Confidential Information. The Parties agree that the Protocol contains
proprietary information regarding the Test Article which is the Confidential
Information of Collaborator. The Collaborator’s Confidential Information
contained in the Protocol shall be subject to the obligations contained in
Article 8 notwithstanding that the Protocol was developed prior to the Effective
Date. Each Party agrees to limit its disclosure of Confidential Information of
the other Party to the amount necessary to carry out the Research Plan or in
accordance with this Article 8. 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 of the other Party agrees to use it
only for the purposes described in the Research Plan or in accordance with this
Article 8. Either Party may object to the designation of information as
Confidential Information by the other Party.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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 or as expressly provided herein. Each Party agrees to use reasonable
efforts to maintain the confidentiality of Confidential Information of the other
Party, which will in no instance be less effort than the Party uses to protect
its own Confidential Information. Each Party may use and disclose such
Confidential Information of the other Party to its employees, contractors,
grantees and agents who have a reasonable need to know such Confidential
Information in exercise of its rights or in performance of its obligations under
this CRADA; provided that such employees, contractors, grantees and agents are
bound by written obligations of confidentiality at least as protective of such
Confidential Information as the terms of this Article 8. 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 the Protocol, this
Agreement, and all applicable laws, rules and regulations for protecting the
rights, safety and welfare of human subjects and for control of new drugs under
investigation. Additional information is available from the HHS Office for Human
Research Protections (http://.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
Article 2 or [*****] 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 Collaborator’s products not yet
commercialized.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

8.7

Publication. The Parties are encouraged to make publicly available the results
of their research and development activities, and IC will use reasonable efforts
to make publicly available the results of the Clinical Trial, including the
relevant Summary Data, as soon as practicable without compromising any right of
publication by IC or its Clinical Research Sites; it being understood that any
presentations at scientific meetings and published abstracts, as well as any
media coverage based thereon, will not compromise any such rights of
publication. The IC and/or the Clinical Investigators will endeavor to present
the results of the Clinical Trial, including the relevant Summary Data, at the
earliest upcoming scientific meeting. Subject to approval (not to be
unreasonably withheld) by the Steering Committee pursuant to this Section 8.7,
Collaborator will be able to disclose such results that are presented at the
above-referenced scientific meeting or thereafter covered by the media in its
own press release or other public disclosure. Before either Party submits a
paper or abstract for publication that includes, or otherwise intends to
publicly disclose, such as in a press release, CRADA Data or information about
CRADA Data or a CRADA Subject Invention that has not been previously published
or publicly disclosed as approved by the Steering Committee pursuant to this
Paragraph 8.7, the other Party will have thirty (30) days to review the proposed
manuscript or other disclosure (except that the other Party will have seven
(7) days to review any proposed oral presentation, abstract or press release) to
assure that Confidential Information is protected. Either Party may request in
writing that the proposed publication or other disclosure be delayed for up to
sixty (60) additional days as necessary to file a Patent Application.
Collaborator understands and agrees that all proposed publications or
disclosures related to the results of the Clinical Trial, including press
releases, must be reviewed and approved (not to be unreasonably withheld) by the
Steering Committee before being submitted for publication or disclosed; provided
that the review process will be conducted as promptly as is practicable.

 

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 IC’s contractors or grantees, as they are not parties to this
CRADA, IC agrees that:

 

  8.8.1

Subject to the other provisions of Article 8 of this CRADA, IC will maintain, to
the extent permitted by law, all CRADA Data as Confidential Information, and
will provide or otherwise make available all CRADA Data to Collaborator for the
exclusive rights to use, disclose and otherwise exploit, and to authorize any
third party to use, disclose and otherwise exploit, all such data for the
development and commercialization of Test Article (including the use of any
CRADA Data in regulatory filings to obtain and maintain regulatory approval
thereof). Subject to Paragraph 8.8.4 below, IC shall not use, disclose or
otherwise exploit, or authorize any third party to use, disclose or otherwise
exploit, any CRADA Data for those purposes. IC will maintain, to the extent
permitted by law, all CRADA Data as Confidential Information, until publication,
and will provide or otherwise make available all CRADA Data to Collaborator for
the non-exclusive rights to use, disclose and otherwise exploit, and to
authorize any third party to use, disclose and otherwise exploit such data for
the development and commercialization of other formulations of the Test Article.
Nothing in this Agreement will prevent any Clinical Research Site or Clinical
Investigator from using their Raw Data for any purpose.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

  8.8.2

With regard to any of Collaborator’s Confidential Information that is provided
to the Clinical Research Sites, IC will require the Clinical Investigators to
agree to confidentiality provisions at least as restrictive as those provided in
this CRADA.

 

  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 NIH CRADA Extramural Investigator/Officer(s). Collaborator will bear
any costs associated with Raw Data provided in formats customized for
Collaborator.

 

  8.8.4

Collaborator’s right to access CRADA Data under Paragraph 8.8 is dependent upon
Collaborator’s continued development and commercialization of Test Article. If
Collaborator fails to continue development or commercialization of Test Article
without the transfer of its development or commercialization efforts to another
party within ninety (90) days of IC’s written request to Collaborator to do so,
IC has the right to make CRADA Data available to a third party.

 

Article 9. Representations and Warranties

 

9.1

Representations of IC IC hereby represents to Collaborator that:

 

  9.1.1

IC has the requisite power and authority to enter into this CRADA and to perform
according to its terms, and that IC’s official signing this CRADA has authority
to do so. IC’s performance of this CRADA in accordance with its terms does not
conflict with any obligations of IC under any agreement with a third party.

 

  9.1.2

To the best of its knowledge and belief, neither IC 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. IC shall not, and the IC will require the Clinical Investigators not to,
knowingly employ, contract with, retain or use any person directly or indirectly
to perform services under this Agreement if such person is debarred pursuant to
the Generic Drug Enforcement Act of 1992, as amended (21 U.S.C. § 301 et. seq.,
or regulations promulgated thereunder or similar laws or regulations in any
applicable ex-U.S. jurisdiction) or that is subject to proceedings that may lead
to such debarment. Should IC, the Clinical Investigators or any such person
directly or indirectly performing services under this Agreement be debarred, or
subject to proceedings that may lead to such debarment during the term of this
CRADA, IC will notify Collaborator within thirty (30) days of when it becomes
aware of any such debarment or proceedings that may lead to debarment.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

9.2

Representations and Warranties of Collaborator. Collaborator hereby represents
and warrants to IC 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 IC 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. IC and Collaborator may terminate this CRADA at
any time by mutual written consent.

 

10.3

Unilateral Termination. Either IC or Collaborator may unilaterally terminate
this CRADA at any time by providing written notice at least [*****] before the
desired termination date.

 

10.4

Effects of Expiration or Termination.

10.4.1 Expiration or Termination by IC or by Collaborator for Safety or Breach.
In the event of expiration of this CRADA, termination of this CRADA by IC for
any reason pursuant to Paragraph 10.3 above, or termination of this CRADA by
Collaborator for reasons of safety concerns or breach by IC or IC’s contractors
or grantees (including the Clinical Research Sites and Clinical Investigators)
of its obligations with respect to the research and development activities to be
carried out under this CRADA, IC shall return to Collaborator any and all funds
provided by Collaborator to IC as of such expiration or termination [*****] and
Collaborator shall have no further obligations to provide any funds to IC after
such expiration or termination.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

10.4.2 Termination by Collaborator for Reasons other than Safety or Breach.
[*****]

 

10.5

New Commitments. Except as expressly provided under Paragraph 10.4 above,
neither Party will incur new costs and expenses related to this CRADA after
expiration, mutual termination, or a written notice of a termination, and will,
to the extent feasible, cancel all outstanding commitments and contracts by the
termination date.

 

10.6

Continuation of Research Plan. If this CRADA is terminated before its
expiration, and the clinical trial to be performed or performed pursuant to the
Research Plan under this CRADA is performed or continues to be performed after
such termination, each Party shall have the rights and licenses to CRADA Data as
set forth herein with respect to any data generated in the performance of such
clinical trial after such termination of this CRADA that would have been
included within the definitions of CRADA Data if this CRADA had not been so
terminated.

 

Article 11. Disputes

 

11.1

Settlement. [*****]

 

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 to the extent possible.

 

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, TEST ARTICLE 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, TEST ARTICLE 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. [*****]

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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. IC 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). IC 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 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 IC 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.

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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

13.6

Amendments. Minor modifications to the Research Plan may be made by the mutual
written consent of the NIH CRADA Extramural Investigator/Officer(s) and CRADA
Collaborator PI(s). 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 shall be assigned or otherwise transferred by either Party without the
prior written consent of the other Party. The Collaborator acknowledges the
applicability of 41 U.S.C. § 15, the Anti Assignment Act, to this Agreement. The
Parties agree that the identity of the Collaborator is material to the
performance of this CRADA and that the duties under this CRADA are nondelegable;
provided, however, that Collaborator may request assignment of this CRADA to an
entity that acquires all or substantially all of the business or assets of
Collaborator related to the Test Article and ICD will not unreasonably deny such
request within a reasonable time period. If IC denies such request or fails to
approve such request within thirty (30) days, Collaborator shall be permitted to
terminate this Agreement immediately upon written notice in accordance with
Paragraph 10.3 above.

 

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 ventures or
partners. Each Party will maintain sole and exclusive control over its personnel
and operations.

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[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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; and each Party shall not unreasonably
withhold making the requested changes of the other Party. 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 IC Materials or IC’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, including the Appendices attached hereto,
constitutes the entire agreement between the Parties concerning the subject
matter of this CRADA and supersedes any prior understanding or written or oral
agreement. Specifically Confidential Disclosure Agreement DK-09-0345 effective
June 23, 2009 (the “Confidentiality Agreement”) is superseded by this CRADA;
provided however, the foregoing shall not be interpreted as a waiver of any
remedies available to either Party as a result of any breach, prior to the
effective date of this CRADA, by the other Party of its obligations pursuant to
the Confidentiality Agreement. All information disclosed by either Party
pursuant to the Confidentiality Agreement shall be deemed to be such Party’s
Confidential Information disclosed hereunder. In the event of any conflict
between this CRADA and any of the Appendices attached hereto, this CRADA shall
control.

 

13.14

Survivability. The provisions of Paragraphs 3.3, 3.4, 4.2, 4.3, 4.4, 6.1-9.2,
10.4, 10.5, 10.6, 11.1, 11.2, 12.1-12.3, 13.1-13.3, 13.7, 13.10 and 13.14 will
survive any expiration or early termination of this CRADA. In addition, the
provisions of Paragraphs 3.1, 3.2, 3.6, 3.7, 3.8, 3.9, 3.10, 3.11, 4.1, 4.5,
13.6, 13.8, 13.9, and 13.11 will survive if the CRADA is terminated early by
Collaborator pursuant to Paragraph 10.3 unless such termination is for safety
concerns.

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

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 IC:

Signature

 

/s/ Griffin Rodgers

   

Date

 

December 15, 2011

 

Griffin P. Rodgers, M.D., M.A.C.P.

       

Director, NIDDK

     

FOR COLLABORATOR:

Signature

 

/s/ Thomas E. Daley

   

Date

 

December 8, 2011

 

Ted Daley

       

President

       

Raptor Therapeutics, Inc.

       

(415) 382-8111 x227

       

tdaley@raptorpharma.com

     

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

CONTACTS INFORMATION PAGE

CRADA Notices

 

For IC:

  

        For Collaborator:

Director, Office of Technology Transfer &

  

        Ted Daley

Development, NIDDK

  

President

12 South Drive (Bldg 12A) Room 3011

Bethesda, MD 20892-5632

  

        Raptor Therapeutics, Inc.

        9 Commercial Blvd., Suite 200

T: (301) 451-3636Novato

  

        CA 94949

MTA@niddk.nih.gov

  

T: (415) 382-8111 ext. 227

  

        tdaley@raptorpharma.com

  

        With a copy to:

  

        Kenneth A. Clark

  

        Attorney, Wilson Sonsini Goodrich and Rosati PC

  

        650 Page Mill Road

  

        Palo Alto, CA 94304

  

        kclark@wsgr.com

Patenting and Licensing

 

For IC:

  

        For Collaborator (if separate from above):

Division Director

  

Division of Technology

  

Development and Transfer

  

NIH Office of Technology Transfer

  

6011 Executive Boulevard, Suite 325

  

Rockville, Maryland 20852-3804

  

Tel: 301-496-7057

  

Fax: 301-402-0220

  

IC Project Officer for Extramural Investigators

 

Name:

  

Edward Doo, MD

Title:

  

Director, Liver Diseases Program

Division:

  

Division of Digestive and Liver Diseases, NIDDK

Address:

  

6707 Democracy Blvd., Room 651

Bethesda, MD 20892-5450

  

Telephone 301-451-4524

  

Email: ed56o@nih.gov

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

SUMMARY PAGE

EITHER PARTY MAY, WITHOUT FURTHER CONSULTATION OR PERMISSION,

RELEASE THIS SUMMARY PAGE TO THE PUBLIC.

 

TITLE OF CRADA:

  

The Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in Children using
Raptor Therapeutics, Inc.’s proprietary Investigational Drug Cysteamine DR
(Cysteamine Bitartrate Delayed-release) - The CyNCh Trial

NIH COMPONENT:

  

National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)

EXTRAMURAL INVESTIGATOR/OFFICER:

  

Edward Doo, M.D.

  

Director, Liver Diseases Program

  

National Institute of Diabetes and Digestive and Kidney Diseases

COLLABORATOR:

  

Raptor Therapeutics, Inc.

COLLABORATOR PRINCIPAL INVESTIGATOR:

  

Patrice Rioux, MD, Chief Medical Officer

TERM OF CRADA:

  

[*****]

ABSTRACT FOR PUBLIC RELEASE:

The National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) of the
National Institutes of Health (NIH) and Raptor Therapeutics, Inc. will
collaborate on a Phase IIb pediatric clinical trial to evaluate whether
treatment with Cysteamine DR results in histologic improvement in children with
Nonalcoholic Fatty Liver Disease (NAFLD).

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

APPENDIX A

[*****]

--------------------------------------------------------------------------------

[*****] Raptor Pharmaceutical Corp. has requested confidential treatment of
certain portions of this offer letter which have been omitted and filed
separately with the U.S. Securities and Exchange Commission pursuant to Rule
24b-2 under the Securities Exchange Act of 1934.

 

APPENDIX B

[*****]