Exhibit 10.1

 

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Double asterisks denote omissions.

 

CLINICAL MANUFACTURING AND SUPPLY AGREEMENT

 

This Clinical Manufacturing and Supply Agreement (this “Agreement”) is entered
into by and between AGILENT TECHNOLOGIES, INC., a Delaware corporation, having a
principal office at 5301 Stevens Creek Blvd., Santa Clara, CA 95051 (“Agilent”)
and OPHTHOTECH CORPORATION, a Delaware corporation, having a principal office at
One Penn Plaza, Suite 1924, New York, NY 10119 (“Customer”) effective as of May
2, 2014 (the “Effective Date”).  Agilent and Customer are each referred to
herein as a “Party” and together as the “Parties”.

 

In consideration of the mutual covenants and promises set forth herein, the
Parties hereby agree as follows:

 

1.                                      SCOPE OF AGREEMENT

 

This Agreement, together with the Quality Agreement (as defined below) specifies
the terms and conditions under which Agilent will manufacture and supply the
Product (as defined below) to Customer and perform Manufacturing Services (as
defined below) for Customer solely for clinical purposes and not for commercial
purposes.

 

2.                                      DEFINITIONS

 

The following capitalized terms will have the meanings given for the purposes of
this Agreement:

 

2.1                                  “Affiliate” means any business entity which
directly or indirectly controls, is controlled by, or is under common control
with any Party to this Agreement.  A business entity shall be deemed to
“control” another business entity if (i) it owns, directly or indirectly, at
least fifty percent (50%) of the issued and outstanding voting securities,
capital stock, or other comparable equity or ownership interest of such business
entity, or (ii) it has the de facto ability to control or direct the management
of such business entity.  If the laws of the jurisdiction in which such entity
operates prohibit ownership by a Party of fifty percent (50%) or more, “control”
shall be deemed to exist at the maximum level of ownership allowed by such
jurisdiction; provided, however, that there is a de facto ability to direct or
control its management.

 

2.2                               “Anti-PDGF Aptamer” means (i) an Aptamer that
binds to platelet-derived growth factor (PDGF) and (ii) intermediates thereof.

 

2.3                               “Active Pharmaceutical Ingredient (API)” has
the meaning set forth in the Quality Agreement.

 

2.4                               “Aptamer” means (i) any pegylated or
unpegylated naturally or non-naturally occurring oligonucleotide that binds to a
Target and (ii) any pegylated or unpegylated oligonucleotide Derived from an
oligonucleotide of clause (i) that binds to a Target.

 

2.5                               “Batch” has the meaning set forth in the
Quality Agreement.

 

2.6                                  “Batch Packet” has the meaning set forth in
the Quality Agreement.

 

2.7                                  “Certificate of Analysis” has the meaning
set forth in the Quality Agreement.

 

2.8                                  “Certificate of Compliance” has the meaning
set forth in the Quality Agreement.

 

2.9                                  “Change Management” means the procedure set
forth in the Quality Agreement.

 

2.10                           “Commercial Supply Agreement” has the meaning set
forth in Section 3.6.

 

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2.11                           “Derived” means identified, obtained, developed,
created, synthesized, designed or resulting from, based upon, containing or
incorporating or generated from or conjugated to or complexed with (whether
directly or indirectly or in whole or in part).

 

2.12                           “Facility” means Agilent’s manufacturing facility
located at Boulder, Colorado, or such other manufacturing site agreed to by the
Parties in writing.

 

2.13                           “FDA” means the United States Food and Drug
Administration or any successor organization.

 

2.14                        “Finished Product” means Customer’s biological or
pharmaceutical drug product that includes the Product.

 

2.15                        “GMP” has the meaning set forth in the Quality
Agreement.

 

2.16                           “Good Condition” means that at the time of
delivery to Customer’s carrier the Product supplied shall: (i) be the right
Product; (ii) be in the right quantity in accordance with the manifest; (iii) be
in the packaging agreed to by the Parties; (iv) be labeled in accordance with
the Product registration; and (v) have no visible defect in the packaging or
seal.

 

2.17                           “Independent Laboratory” means a laboratory
independent of each Party, mutually agreed in writing between the Parties and
competent to determine the matters referred to in Section 8.2.3.

 

2.18                        “Initial Order” has the meaning set forth in Section
4.1.

 

2.19                        “Initial Term” has the meaning set forth in Section
13.1.

 

2.20                        “Intellectual Property” means, collectively,
Patents, Marks, copyrights, Know-How, and any other intellectual property owned
or licensed by a Party.

 

2.21                        “Kilos” means kilos of oligo weight.

 

2.22                        “Know-How” means all non-patented and proprietary:
information, inventions, developments, techniques, materials, processes,
manufactures, compositions of matter or methods of use and trade secrets,
whether or not patentable or copyrightable.  Know-How excludes (i) Patents and
(ii) any of the foregoing which would be excluded from the definition of
Proprietary of Information under Section 5 of the Confidentiality Agreement.

 

2.23                           “Latent Defect” means a failure of Product to
meet the Specification at the time of delivery, which failure is subsequently
detected and (i) is not attributable to a defect in the PEG delivered to Agilent
by Customer for use in the Product, which defect in the PEG was not discoverable
by Agilent in the course of testing in accordance with Agilent’s Standard
Operating Procedure; (ii) is not attributable to a fundamental chemical or
stability defect in the Product that results in a change in the Product that
occurs after delivery by Agilent; and (iii) is not the result of further
processing, storage, handling or use of the Product after delivery by Agilent.

 

2.24                           “Licensed Patent(s)” means any Patent owned by
Agilent as of the Effective Date or during the Term claiming or covering the
Process.

 

2.25                        “Manufacturing Services” means those manufacturing
services set forth in a Statement of Work to be performed by Agilent with
respect to Product and Finished Product, including the development and
validation of analytic methods, stability testing and release.

 

2.26                        “Manufacturing Standards” has the meaning set forth
in Section 5.2.

 

2.27                        “Marks” means the trademarks, service marks, trade
dress, trade names, logos, insignia, symbols, designs or other marks identifying
either Party or its products.

 

2.28                           “Master Batch Record” has the meaning set forth
in the Quality Agreement.

 

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2.29                        “Patents” means patents, patent applications and any
issued divisions, continuations, continuations-in-part, re-issues,
re-examinations, renewals or extensions thereof and any foreign counterpart of
any of such U.S. patents.

 

2.30                        “Person” means any individual, partnership,
corporation, limited liability company, unincorporated organization or
association, any trust or any other business entity.

 

2.31                        “Process” or “Processing” means the combination of
materials, procedures, test methods and controls used by Agilent to manufacture
the Product under this Agreement, that includes the following unit operations: 
[**].

 

2.32                        “Product” means (i) the Aptamer described in Exhibit
A and intermediates thereof, and (ii) any future compounds as mutually agreed to
by the Parties in a written amendment to this Agreement.

 

2.33                           “Proprietary Information” has the meaning set
forth in Section 14.1.1.

 

2.34                        “Purchase Order” means a written purchase order in
substantially the form agreed in good faith based on customary arrangements in
the biotechnology industry between Agilent and Customer, to be delivered by
Customer to Agilent for Product or services pursuant to this Agreement.

 

2.35                        “Quality Agreement” means the agreement by and
between Agilent and Customer, dated as of the Effective Date, executed by duly
authorized representatives of each Party, setting forth the obligations of the
Parties with respect to quality matters applicable to the manufacturing and
supply of the Product and Customer’s drug product testing under this Agreement,
attached hereto as Exhibit C.

 

2.36                           “Regulatory Authority” has the meaning set forth
in the Quality Agreement.

 

2.37                           “Renewal Term” has the meaning set forth in
Section 13.1.

 

2.38                           “Specification” means the specification for the
Product as set forth in a Statement of Work, which specification may be amended
from time to time in accordance with this Agreement.

 

2.39                        “Statement of Work” means (i) any of the statements
of work identified in Exhibit E; and (ii) any future statement of work as
mutually agreed to by the Parties.

 

2.40                        “Target” means a protein, cytokine, enzyme,
receptor, transducer, transcription factor, antigen or any other non-nucleic
acid molecule.

 

2.41                           “Term” has the meaning set forth in Section 13.1.

 

2.42                        “Third Party” means any Person who is not a Party or
an Affiliate of a Party.

 

3.                                      OBLIGATIONS OF THE PARTIES; STATEMENTS
OF WORK

 

3.1                               Obligations of Agilent.  Agilent will
manufacture and supply the Product to Customer and perform the Manufacturing
Services at the Facility in accordance with the terms of this Agreement, the
Quality Agreement, any applicable Statement of Work and in accordance with GMP
and all laws and regulations applicable to the manufacture and supply of the
Product at the Facility and the performance of the Manufacturing Services. 
Agilent shall perform the Manufacturing Services in a professional and
workmanlike manner consistent with industry standards.  Agilent will deliver the
Product in accordance with the delivery schedules set forth in, as applicable,
the Initial Order and each subsequent accepted Purchase Order.

 

3.2                               Obligations of Customer.   Customer will
provide Agilent with information, material and cooperation reasonably necessary
for the manufacture and supply of the Product in accordance with the Statement
of Work and the Quality Agreement.

 

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3.3                               PEG Supply Agreement.  Without limiting the
generality of Section 3.2, during the Term, Customer shall use commercially
reasonable efforts to maintain the License, Manufacturing and Supply Agreement
between Customer and Nektar Therapeutics, Corporation (“Nektar”), dated
September 30, 2006, as amended, (the “PEG Supply Agreement”), or enter into an
agreement with Nektar or another Third Party to obtain supply of poly ethylene
glycol (“PEG”) for the E10030 molecule.  For purposes of clarity, Customer may
terminate the PEG Supply Agreement with Nektar; provided that Customer has
obtained an alternative source of supply of PEG  and provided further that
Agilent shall not be liable for any delays or supply failures associated with
such termination and retention of an alternative source of supply of PEG. 
Customer shall reimburse Agilent for any reasonable direct costs incurred by
Agilent to qualify any alternative source of supply of PEG.  Customer and
Agilent shall cooperate to ensure that Customer’s orders of PEG to be delivered
to Agilent from Nektar (or such alternative Third Party) are (i) in sufficient
amounts to enable Agilent to manufacture Product ordered by Customer hereunder;
and (ii) in conformance with the forecasting and order procedure set forth in
the PEG Supply Agreement.  During the Term, Customer shall provide Agilent
copies of proposed forecasts for PEG (redacted to remove confidential
information or commercially sensitive information) at the time of submission to
Nektar (or such alternative Third Party).  Within [**] business days after
receipt of any such PEG forecast, Agilent shall provide written notice to
Customer of any adjustments to such forecast that Agilent reasonably deems
necessary in order to ensure a supply of PEG necessary to manufacture Product to
fulfill Customer’s requirements of Product hereunder.  Within [**] business days
after receipt of written notice from Agilent, Customer shall provide Agilent
with written confirmation (which may be by e-mail) that either (i) Customer has
submitted a forecast revised pursuant to Agilent’s notice and whether Nektar has
accepted such revised forecast, or (ii) Customer does not agree such revised
forecast is required in which case the Parties will meet to determine what
adjustments, if any, are required to the forecast and upon such determination
Customer shall submit such revised forecast to Nektar if so agreed by the
Parties.

 

3.4                               Statements of Work.  From time to time during
the Term, Customer may request that Agilent perform certain Manufacturing
Services for the Product.  As mutually agreed by the Parties in a Statement of
Work, each Party shall perform the obligations set forth in each Statement of
Work.  In the event of any inconsistency between this Agreement and a Statement
of Work, the terms and conditions of this Agreement shall prevail.  Each Party
shall retain appropriately qualified and trained personnel with the requisite
knowledge and experience to perform such obligations in accordance with this
Agreement.  Agilent may, with the prior written consent of Customer, subcontract
or delegate its obligations under this Agreement to perform the services;
provided, that any subcontractor shall be subject to the same obligations and
other provisions contained in this Agreement or any applicable Statement of
Work.  Customer and Agilent acknowledge and agree that the Statements of Work
entered into prior to the Effective Date and identified in Exhibit E and the
Initial Orders shall be governed by the terms and conditions of this Agreement
and that references to the Agilent supply and service agreement terms and
conditions in such Statements of Work shall be deemed references to this
Agreement.

 

3.5                               Exclusivity.

 

3.5.1                     Except as otherwise provided in Section 13.3.1,
Agilent agrees that (a) during the Term and (b) provided that the Commercial
Supply Agreement is in effect between the Parties, for a five (5) year period
after the Term (the “Exclusivity Period”), Agilent shall only supply Anti-PDGF
Aptamer APIs or Finished Product to Customer and any Affiliate of Customer or
Third Party designated by Customer.

 

3.5.2                     Customer agrees that during the Term, Agilent shall be
Customer’s supplier of at least [**] percent ([**]%) of Customer’s clinical
requirements of Product for use in the United

 

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States, European Union, and any additional future jurisdictions as mutually
agreed to by the Parties in writing.

 

3.6                               Commercial Supply Agreement.  Within [**] days
following the execution of this Agreement, the Parties shall negotiate in good
faith and use commercially reasonable efforts to enter into a commercial
manufacturing supply agreement for the commercial supply of Product, which
agreement shall include the terms set forth in Exhibit I and other commercially
reasonable terms mutually agreed to by the Parties (“Commercial Supply
Agreement”).

 

4.                                      SUPPLY

 

4.1                               Initial Orders.  The Parties acknowledge that
Customer has submitted, and Agilent has accepted, the initial Purchase Orders
for Product attached hereto as Exhibit B (the “Initial Orders”).  Customer may
not make changes to or cancel the Initial Orders without Agilent’s prior written
consent.

 

4.2                               Forecasts.  Commencing on the Effective Date
and every [**] months thereafter, Customer shall submit to Agilent a written
rolling forecast of the quantity of Product which Customer expects to order from
Agilent over the next [**] months (“Forecast”).  The Forecast shall constitute a
non-binding, good faith estimate provided by Customer solely to assist Agilent
in production planning, and shall not represent any purchase commitment by
Customer or a supply commitment by Agilent.  It is understood and agreed by the
Parties that Agilent will not hold inventory of Product.  However, Agilent shall
deliver such quantities of Product that are ordered in accordance with a binding
Purchase Order that has been accepted by Agilent, provided that such Purchase
Order is in accordance with the lead times set forth in Sections 4.3.1.

 

4.3                               Future Orders.

 

4.3.1                        During the term of this Agreement, Customer may
place Purchase Orders with Agilent.  Each such Purchase Order shall be submitted
by Customer (i) no later than [**] months prior to the requested delivery date
for large scale production (i.e., [**] Kilos or greater) and (ii) no later than
[**] months prior to the requested delivery date for all other Purchase Orders. 
Customer may not increase the quantity of Product ordered under a Purchase Order
without the prior written consent of Agilent.  Notwithstanding the foregoing,
Agilent shall use commercially reasonable efforts to fill an increased Purchase
Order upon receiving Customer’s written request therefor.

 

4.3.2                        Acceptance of Purchase Orders.  Agilent shall
notify Customer as to whether any Purchase Order delivered pursuant to Section
4.3.1 has been accepted or rejected within [**] business days following
Agilent’s receipt of such Purchase Order.  Agilent may only reject a Purchase
Order that (i) is not in compliance with this Agreement; (ii) does not have a
delivery address; (iii) does not comply with Agilent’s credit limit standards
(consistent with Agilent’s corporate policy); provided that if Customer agrees
to make an up-front payment with respect to such Purchase Order, Agilent may not
reject the Purchase Order on the basis that it does not comply with Agilent’s
credit limit standards; or (iv) does not comply with the lead times set forth in
Section 4.3.1.  Agilent’s failure to affirmatively reject a Purchase Order
within the [**] business day period shall be deemed an acceptance of such
Purchase Order.  In the event that Agilent rejects a Purchase Order hereunder,
Agilent shall notify Customer in writing within [**] business days of the
reasons why such Purchase Order was rejected by Agilent.  Customer may, at its
option, submit a revised Purchase Order.

 

4.3.3                        Details for Purchase Orders.  Each Purchase Order
shall specify Product ordered and the time, manner and address of delivery, all
of which shall be subject to this Article 4.

 

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4.3.4                        Fulfillment of Purchase Orders.  Agilent will use
commercially reasonable efforts to complete the Manufacturing Services
(including without limitation delivery of any Batch) by the timeframe estimated
in the applicable Statement of Work and Purchase Order.  Customer expressly
acknowledges that delivery dates are approximate.  Agilent’s failure to complete
the Manufacturing Services or deliver any Batch by any specified date will not
be sufficient cause for cancellation of the Purchase Order by Customer, nor will
Agilent be liable for any direct, indirect, consequential, or economic loss or
damages due to delay in delivery.  Notwithstanding the foregoing, in the event
that Agilent (i) fails to complete the Manufacturing Services or deliver a Batch
by the date specified in the applicable Statement of Work and Purchase Order and
(ii) fails to use commercially reasonable efforts to promptly complete the
Manufacturing Services or deliver a Batch after such date, Customer shall have
the right to cancel such Statement of Work or Purchase Order.

 

4.4                               Delivery and Acceptance.  Subject to Section
8.2.2, Agilent will deliver the Product to the carrier selected by Customer. 
Shipment terms are FCA Agilent’s Dock Boulder (Incoterms 2010).  Title and risk
of loss will pass to Customer when the Product is delivered to Customer’s
carrier.  Customer is responsible for payment of all shipment costs, including
any insurance necessary to guard against loss or damage during shipment. 
Acceptance shall occur upon delivery of the Product to Customer’s carrier.

 

4.5                               Certificates.  An appropriate Certificate of
Analysis (which shall include a material safety data sheet) and Certificate of
Compliance shall be provided with the shipment of each Batch delivered to
Customer.

 

4.6                               Shipping Instructions.  Customer will provide
Agilent with packaging and shipping instructions including temperature
requirements, temperature monitoring instructions and packaging specifications. 
Notwithstanding any other provision of this Agreement, Agilent will not be
liable for any loss or damage caused by Agilent’s compliance with Customer’s
packaging and shipping instructions or any loss or damage caused by Customer’s
carrier.

 

5.                                      PROCESSING OF PRODUCT

 

5.1                                  Storage and Handling.  Agilent shall store
and handle the raw materials and packaging components under appropriate
conditions and temperature, humidity, light and cleanliness to avoid any
material adverse effect on the identity, strength, quality and purity of such
materials and components.  Agilent shall store and handle the Product in
accordance with the Specification and under appropriate conditions as defined by
Customer in accordance with the Product stability studies and temperature,
humidity, light and cleanliness to avoid any material adverse effect on the
identity, strength, quality and purity of the Product.

 

5.2                                  Manufacturing Standards.  Agilent shall
manufacture the Product in conformity with the Process, Master Batch Record, GMP
and the Specification (the “Manufacturing Standards”).

 

5.3                                  Shortage of Supply.  Agilent shall notify
Customer immediately upon becoming aware of an event of force majeure under
Article 12 or any other event that would render Agilent unable to supply any
quantity of the Product required to be supplied hereunder.  In such event,
Agilent shall use commercially reasonable efforts to remedy such shortage,
including allocating a pro-rata portion of any available materials or
prioritizing capacity based on the production of the Product for Customer and
the production of products for Agilent’s other customers according to the
relative quantities ordered during the immediately preceding [**] months prior
to such shortage; provided, however, that Customer shall receive treatment
proportionately no less

 

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favorable than any of Agilent’s other customers with respect to allocation of
such materials or prioritization of capacity.

 

5.4                                  Safety Stock.  Except with respect to the
supply of PEG, Agilent shall at its own risk and expense, maintain a supply of
raw materials and components necessary for the manufacture of Product based on
accepted Purchase Orders.

 

5.5                                  Alternative Supplier.  Agilent acknowledges
that (i) it is the intent of Customer to establish an alternative supplier to
manufacture Product and (ii) in the process of establishing such an alternative
supplier Customer will discuss the Product and Customer’s Know-How, subject to
Article 14.  Customer shall be free to disclose to any such actual or proposed
alternative supplier the Process overview set forth in Exhibit H.

 

5.6                                  Process Changes.  Agilent agrees that no
change to the Process shall be made without the prior written approval of
Customer.  Notwithstanding the foregoing, any such change to the Process shall
be subject to the agreed upon Change Management process as set forth in the
Quality Agreement and the prior mutual agreement of the Parties with respect to
the costs and expenses associated with the agreed upon change.

 

6.                                      PRICE AND PAYMENT

 

6.1                               Pricing.  Pricing for the Product shall be as
set forth in each Statement of Work; provided that such pricing shall not exceed
the pricing for Product set forth in Exhibit J except to the extent that the
Manufacturing Standards as of the Effective Date for Product ordered are
materially modified pursuant to the Change Management provisions set forth in
the Quality Agreement; provided that any increase in pricing shall be
proportionate to the increase in Agilent’s costs to manufacture Product based on
such modified Manufacturing Standards.

 

6.2                                  Payment.  Agilent shall invoice Customer at
the time of, as applicable, shipment of the Product in accordance with this
Agreement or completion of the Manufacturing Services, unless otherwise agreed
to by the Parties in a Statement of Work.  Payment of an invoice for Product is
due [**] days from the date of Customer’s receipt of invoice.

 

6.3                               Taxes.  Prices are exclusive of any sales,
use, service, value added or other taxes.  Any tax, duty, custom, insurance or
other fee of any nature imposed on Product or services by any federal, state,
local or foreign governmental authority shall be paid by Customer.  If Agilent
is required to pay any such tax or fee, Customer will reimburse Agilent promptly
upon invoice by Agilent.  If Customer claims exemption from any taxes, Customer
will provide Agilent with an appropriate exemption certificate for the delivery
jurisdiction.

 

6.4                               Remedies.  Agilent may temporarily discontinue
its performance of the manufacture and supply obligations under this Agreement
if Customer fails to pay any sum when due and Customer has not cured such
failure within [**] business days after receipt of written notice from Agilent
identifying such failure.

 

7.                                      WARRANTIES

 

7.1                                  General Warranties.  Each Party warrants to
the other Party that (i) it has the right and authority to enter into this
Agreement and to carry out its obligations hereunder; (ii) it is validly
existing in each jurisdiction in which it is incorporated and is authorized to
do business under the laws of each jurisdiction in which it engages in business
activities; and (iii) it is not aware of any legal,

 

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contractual or other restriction, limitation or condition that might adversely
affect its ability to perform its obligations hereunder.

 

7.2                                  Warranties by Agilent.  Notwithstanding any
prior acceptance of Product by Customer in accordance with Section 4.4 Agilent
warrants to Customer that (i) all Product supplied under this Agreement shall
conform to the Specification at the time of delivery to Customer’s carrier; and
(ii) all Product delivered hereunder shall be delivered to Customer free and
clear of all liens and security interests.

 

7.3                               Warranties by Customer.  Customer warrants to
Agilent that (i) it owns or has the necessary rights, title and interest in and
to the Product, including the right under Patents owned or controlled by
Customer to have Product made for Customer, and (ii) as of the Effective Date,
Customer has not received any written notification alleging that the Product
infringes the intellectual property rights of any Third Party.

 

7.4                               Remedies.  In the event that the Product
supplied under this Agreement did not conform to the Specification at the time
of delivery to Customer’s carrier, or the Product delivered to Customer was not
free and clear of all liens and security interests, Customer shall have the
remedies set forth in Section 8.2.3.6.

 

7.5                               No Warranty to Third Parties.   The warranties
set forth in Section 7.2 are solely for the benefit of Customer.  Agilent makes
no warranty to Customer’s end-user customers or any other Third Party.  Customer
will not pass on to any end-user customer or any other Third Party any warranty
or representation on behalf of Agilent.

 

7.6                               DISCLAIMER.  THE ABOVE WARRANTIES ARE
EXCLUSIVE AND EXCEPT AS EXPRESSLY PROVIDED HEREIN, NEITHER PARTY MAKES NOR
RECEIVES ANY WARRANTY OF ANY KIND, EXPRESS, IMPLIED, STATUTORY OR OTHERWISE,
INCLUDING WARRANTIES OF DESIGN, SUITABILITY OF QUALITY, OR ARISING FROM A COURSE
OF DEALING OR USAGE OF TRADE PRACTICE, WITH REGARD TO THE PRODUCT. AGILENT
SPECIFICALLY DISCLAIMS THE IMPLIED WARRANTIES OF MERCHANTABILITY,
NON-INFRINGEMENT AND FITNESS FOR A PARTICULAR PURPOSE.

 

8.                                      QUALITY

 

8.1                                  Quality Agreement.  Each Party will comply
with the terms of the Quality Agreement in the performance of its obligations
hereunder including record retention, audits and inspections, change control,
adverse events and product recall.  The Parties will conduct periodic Product
quality reviews in accordance with the terms of the Quality Agreement.

 

8.2                                  Quality Assurance.

 

8.2.1                        Testing by Agilent.  Agilent shall perform quality
testing using assays, including assays developed under a Statement of Work,
mutually agreed to by the Parties in order to assure that Product complies with
the Specification as set forth in the applicable Statement of Work, and shall
retain samples of Product as required by applicable law and produce records of
the tests made on each Batch.  Agilent shall provide Customer a Certificate of
Analysis and Certificate of Compliance confirming the performance of such
testing. Customer may elect, at its sole discretion, to attend and observe any
testing conducted by Agilent in accordance with this Section 8.2.1.  The Parties
agree that the initial testing specifications for Product are as set forth in
the related Statement of Work.  In addition, no Product shall be delivered until
such Product has been Processed in

 

8

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accordance with the agreed upon testing specifications; provided, however, that
the foregoing shall not relieve Agilent of its obligation under this Section
8.2.

 

8.2.2                        Records.  Agilent shall maintain records, including
Master and Batch Production Records, with respect to the manufacturing and
quality testing of the Product and shall deliver the Executed Batch Record to
Customer electronically prior to shipment of the associated Batch of Product. 
Agilent shall not ship Product hereunder unless and until: (i) Agilent has
provided to Customer the Executed Batch Record for such Product and under the
condition that all opened deviations, investigations or other anomalous events
related to such Batch have been resolved, and (ii)  Customer has reviewed the
Executed Batch Record for such shipment and authorized such shipment in
writing.  Agilent shall promptly respond to any questions or requests for
additional information that Customer may have with respect to such Executed
Batch Record.  Notwithstanding the foregoing, in the event that (a) Customer
fails to provide such authorization within [**] business days after Customer’s
receipt of the Executed Batch Record and (b) Customer has not within such [**]
business day period submitted to Agilent any questions or requests for
information and (c) Customer does not within such [**] business day period find
fault or anomaly with the balance of the Batch Packet documentation, then
Agilent may ship the associated Batch of Product and Customer shall be deemed to
have accepted the Executed Batch Record.  Agilent shall provide Customer with
the remaining Batch Packet documentation (i.e., the records and documentation
identified in Sections 2.1.6.2 through 2.1.6.7 of the Quality Agreement) at
least [**] business days prior to the proposed Product shipment date. Such
records shall also be made available to Customer during normal business hours,
upon prior written request.

 

8.2.3                        Non-Conforming Product.  Notwithstanding any prior
acceptance of Product or the Batch Packet by Customer in accordance with
Sections 4.4 or 8.2.2, the following shall apply with respect to non-conforming
Product:

 

8.2.3.1              Inspection/Testing.  Upon receipt of each delivery of
Product from Agilent under this Agreement, Customer shall report to Agilent
within [**] business days of Customer’s receipt of Product if the Product does
not conform to the quantity specified in the Purchase Order, or if the Product
is otherwise not in Good Condition.

 

8.2.3.2              Failure to Conform to the Quantity; Good Condition.  In the
event Customer notifies Agilent pursuant to Section 8.2.3.1 that the quantity of
Product delivered does not conform to the quantity specified in the Purchase
Order, Agilent shall deliver, at Agilent’s expense, such additional quantity of
Product as is necessary to meet the quantity specified in the Purchase Order as
soon as reasonably practicable.  In the event Customer notifies Agilent pursuant
to Section 8.2.3.1 that the Product is not in Good Condition at the time of
delivery, Agilent shall have the right to inspect and analyze the Product.  In
the event that the Parties agree that the Product was not in Good Condition at
the time of delivery, Customer shall have the remedies as set forth in Section
8.2.3.6. If the Parties cannot agree as to whether the Product was in Good
Condition at the time of delivery, the matter shall be escalated in accordance
with Section 16.b, Escalated Dispute Resolution.

 

9

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8.2.3.3              Latent Defect.  In the event Customer discovers that the
Product has a Latent Defect, Customer shall promptly notify Agilent in writing
providing specific details about the nature of the Latent Defect.

 

8.2.3.4              Notification from Customer.  In the event Customer notifies
Agilent pursuant to Section 8.2.3.3 that the Product has a Latent Defect, (i)
Agilent shall have the right to inspect and analyze the Product and (ii) the
Parties shall work together in good faith to reach agreement as to whether the
Product has a Latent Defect.  In the event the Parties agree that the Product
has a Latent Defect, Customer shall have the remedies as set forth in Section
8.2.3.6.

 

8.2.3.5              Independent Laboratory.  In the event the Parties fail to
agree whether the Product has a Latent Defect, the matter shall be referred to
an Independent Laboratory.   Agilent shall forward a sample of retained Product
from the Batch in question to the Independent Laboratory for testing and control
purposes.  The Parties shall mutually agree to the controls and procedures used
by the Independent Laboratory to test the Product.  Agilent shall have the right
to audit the Independent Laboratory to determine whether there was any departure
from the established controls and procedures used to test the Product.  In the
event Agilent determines that there was a departure from the established
controls and procedures, Agilent shall notify Customer in writing within [**]
business days and the Parties shall resolve the matter in accordance with
Section 16.b.  In the absence of such determination by Agilent, the decision of
the Independent Laboratory shall be final and binding on the Parties.  If the
Independent Laboratory determines that the Product has a Latent Defect, then the
Independent Laboratory’s fees shall be borne by Agilent.  If the Independent
Laboratory determines that the Product does not have a Latent Defect, then
Customer shall bear the Independent Laboratory’s fees and reimburse Agilent for
any reasonable direct costs incurred by Agilent in connection with the
Independent Laboratory’s analysis of the Product.

 

8.2.3.6              Customer’s Remedies.  The following remedies shall be
available to Customer in the event the Product was not in Good Condition at the
time of delivery to Customer’s carrier or that the Product has a Latent Defect:

 

8.2.3.6.1                         Agilent may elect either to collect and
dispose of the affected Product, at Agilent’s expense, or to reimburse Customer
for any reasonable costs incurred by Customer to collect and dispose of the
affected Product;

 

8.2.3.6.2                         Agilent shall reimburse Customer for all
reasonable costs incurred by Customer in connection with delivery of the
affected Product, including freight, clearance, duty and storage charges
incurred by Customer; and

 

8.2.3.6.3                         Agilent shall promptly, at no additional cost
to Customer (subject to Section 15.3), (i) replace the affected Product as soon
as reasonably practicable with Product that meets the requirements of Section
3.1 or (ii) rework the affected Product, subject to mutual agreement of the
Parties.  In the event that Agilent fails to replace the affected

 

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Product within the timeframe mutually agreed to by the Parties, Agilent will
refund to Customer any amounts paid for such Product.

 

8.2.4                        Audit Rights.  Customer shall have the right to
conduct audits and inspections of the Facility, Agilent’s manufacturing
operations and Agilent’s records relating to this Agreement as provided in the
Quality Agreement.  Agilent shall reasonably cooperate with Customer in
conducting such audits and inspections.

 

8.2.5                        Observation by Customer.  During the Term, Customer
shall have the right, at Customer’s sole cost and expense, during normal
business hours and upon reasonable notice, to visit the Facility in order to
ensure that the Processing complies with applicable legal requirements and the
Specification, as applicable. Agilent shall reasonably cooperate with Customer
to permit Customer such access in connection with such visits.  At all times
while in attendance at the Facility, Customer agrees to comply with all Agilent
health and safety protocols and other policies and procedures applicable to
visitation of the Facility as notified by Agilent to Customer prior to or during
such attendance.  Such visits shall not interfere with Agilent’s operations.

 

8.2.6                        Recalls and Voluntary Withdrawals.  If either Party
becomes aware of information about the Product or Finished Product indicating
that it may be non-conforming Product or that there is potential adulteration,
misbranding and/or any potential issues regarding the safety or effectiveness of
the Product or Finished Product, it shall within [**] hours provide notice to
that effect to the other Party.  Customer will initiate an investigation and
assessment of such circumstances and shall promptly notify Agilent of its
findings and any proposed course of action.  The Parties shall meet to discuss
such circumstances and to consider appropriate courses of action.  Customer
shall bear all costs associated with a recall of the Product or Finished Product
unless such recall is caused by Agilent’s gross negligence or willful misconduct
or the failure of Product to conform to the Specification or GMP requirements at
the time of delivery to Customer’s carrier, in which case Agilent shall pay all
costs associated with the recall, subject to Article 15.

 

9.                                      INTELLECTUAL PROPERTY

 

9.1                               Background Property.  Each Party retains all
right, title and interest in and to all Intellectual Property owned, licensed or
developed by or on behalf of such Party prior to the Effective Date or
independent of this Agreement, and without reliance on the other Party’s
Proprietary Information.

 

9.2                               Ownership of Developed Intellectual Property.

 

9.2.1                        Customer shall be the sole owner of all right,
title and interest in and to all Intellectual Property relating specifically to
the Product, including the Specification and all improvements to the Product and
Specification that are (i) jointly developed by Customer or its employees or
consultants on the one hand and Agilent or its employees or consultants on the
other hand, during the course of performing or receiving services hereunder  or
(ii) developed by Agilent or its employees or consultants during the course of
performing Manufacturing Services under a Statement of Work or during the course
of performing services for Customer under any Purchase Order, including the
Initial Orders, ((i) and (ii) collectively, “Product Improvements”).  Agilent
hereby assigns to Customer all of its right, title and interest in Product
Improvements.  Agilent agrees to execute such assignments and other documents
and to take such other actions as may be reasonably requested by Customer from
time to time, at Customer’s expense, in order to effect the ownership provisions
of this Section 9.2.1.  For avoidance of doubt,

 

11

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intellectual property relating to the Processing of nucleic acids and the
Processing of modified nucleic acids, including pegylated nucleic acids, which
is not sequence or Product specific shall not be considered to be a “Product
Improvement” but shall be considered to be Intellectual Property relating to the
Process, as provided in Section 9.2.2 below and not subject to the obligation to
assign provided in this Section 9.2.1.

 

9.2.2                        Agilent shall be the sole owner of all right, title
and interest in and to all Intellectual Property relating to the Process,
including all improvements thereto, that are developed by Agilent or its
employees or consultants.   In addition, Agilent shall be the sole owner of all
right, title and interest in and to all Intellectual Property relating to the
Process, including all improvements thereto, that are jointly developed by
Customer or its employees or consultants and Agilent or its employees or
consultants, during the course of performing or receiving services hereunder
(“Joint Process Improvements”).  Customer hereby assigns to Agilent all of its
right, title and interest in Joint Process Improvements, except as otherwise
provided in Section 9.3.2.1 below.  Customer agrees to execute such assignments
and other documents and to take such other actions as may be reasonably
requested by Agilent from time to time, at Agilent’s expense, in order to effect
the ownership provisions of this Section 9.2.2.

 

9.3                               License Grants.

 

9.3.1                        License to Agilent.

 

9.3.1.1              During the Term, Customer hereby grants to Agilent a fully
paid, non-exclusive, non-sublicensable (except as otherwise permitted under
Section 9.5), non-transferable (except to a permitted assignee in accordance
with Section 16(e) (“Permitted Assignee”)) license under any and all Customer
Intellectual Property that is necessary for Agilent to perform its obligations
under this Agreement, for the sole and limited purpose of Agilent’s performing
its obligations under this Agreement.

 

9.3.2                        Licenses to Customer.

 

9.3.2.1              Agilent hereby grants to Customer a worldwide, fully
paid-up, royalty-free, perpetual, non-sublicensable (except in accordance with
this Section 9.3.2.1), non-transferable and non-assignable (except to a
Permitted Assignee), (x) non-exclusive license under Joint Process Improvements;
and (y) non-exclusive license under analytical methods that are developed by
Agilent in the performance of a Statement of Work (including Statements of Work
dated prior to the Effective Date that are identified in Exhibit E) or a
Purchase Order, including the Initial Orders, (“Analytical Methods”) (together
with Joint Process Improvements, collectively, “Licensed Technology”) to
manufacture, have manufactured, produce, have produced, develop, have developed,
use, have used, offer for sale, have offered for sale, sell, have sold, import,
and have imported the Product and Finished Product, subject to the following:
(i) any sublicense granted by Customer to a Third Party manufacturer or a Third
Party that Customer has granted a license under Customer Intellectual Property
to clinically develop Product (“Customer Licensee”) and/or Finished Product
shall be restricted to using the Licensed Technology for the sole purpose of
performing services (including development and manufacturing services) for the
Product or Finished Product exclusively for Customer, Customer’s Affiliates,
Customer Licensees or a Permitted Assignee and (ii) prior to disclosing any
Licensed Technology to any Third Party, Customer shall enter into a valid
written confidentiality agreement with such Third Party that (a) requires the

 

12

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Third Party to maintain the confidentiality of Agilent Proprietary Information
contained in the Licensed Technology under terms no less restrictive than those
set forth in Article 14 of this Agreement and (b) restricts the Third Party from
using the Licensed Technology for any purpose other than to perform services for
the Product or Finished Product exclusively for Customer, Customer’s Affiliates,
Customer Licensees or a Permitted Assignee in accordance with this Section
9.3.2.1.  In addition, any sublicense to Analytical Methods granted by Customer
under this Section 9.3.2.1 to a Third Party manufacturer of Finished Product
shall be restricted to those Analytical Methods that are necessary to
manufacture and release the Finished Product.  In addition to the non-exclusive
license granted above, and solely with respect to Joint Process Improvements,
Agilent hereby grants to Customer  a worldwide, fully paid-up, royalty-free,
perpetual, non-sublicensable (except in accordance with this Section 9.3.2.1),
non-transferable and non-assignable (except to a Permitted Assignee) license to
use Joint Process Improvements on a non-exclusive basis to manufacture, have
manufactured, produce, have produced, develop, have developed, use, have used,
offer for sale, have offered for sale, sell, have sold, import, and have
imported products controlled by Customer, provided that (i) any sublicense
granted by Customer to a Third Party manufacturer or a Customer Licensee shall
be restricted to using the Joint Process Improvements for the sole purpose of
performing services (including development and manufacturing services)
exclusively for Customer, Customer’s Affiliates, Customer Licensees or a
Permitted Assignee and (ii) prior to disclosing any Joint Process Improvements
to any Third Party, Customer shall enter into a valid written confidentiality
agreement with such Third Party that (a) requires the Third Party to maintain
the confidentiality of Agilent Proprietary Information contained in the Joint
Process Improvements under terms no less restrictive than those set forth in
Article 14 of this Agreement and (b) restricts the Third Party from using the
Joint Process Improvements for any purpose other than to perform services
exclusively for Customer, Customer’s Affiliates, Customer Licensees or a
Permitted Assignee in accordance with this Section 9.3.2.1. Except as expressly
provided herein, no license to any Licensed Technology is granted, conveyed or
implied. [**].

 

9.3.2.2              Agilent hereby grants to Customer a non-exclusive,
royalty-free, non-sublicensable (except in accordance with this Section
9.3.2.2), non-transferable and non-assignable (except to a Permitted Assignee)
license, under the Licensed Patents, to make, have made, use, import, offer for
sale and sell the Product and Finished Product, subject to the following:  any
sublicense granted by Customer to a Third Party manufacturer or Customer
Licensee shall be restricted to developing and manufacturing the Product or
Finished Product exclusively for Customer, Customer’s Affiliates, Customer
Licensees or a Permitted Assignee and shall contain a provision identifying
Agilent as an intended third party beneficiary of, and entitled to enforce, any
such sublicense. No other license is granted by Agilent under this Agreement,
either directly or by implication, under any Patent other than the Licensed
Patents.   [**].

 

9.3.2.3              Upon the written request of Customer and provided that the
Commercial Supply Agreement is in effect between the Parties, Agilent hereby
grants to Customer a non-exclusive, royalty-bearing, non-sublicensable (except
to a Third Party manufacturer or Customer Licensee in accordance with this
Section 9.3.2.3), non-transferable and non-assignable (except to a Permitted
Assignee) license,[**].  In the event that Customer exercises its right to such
a license:  (i)

 

13

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[**] of this Agreement, [**], and [**]; and [**].  In addition, [**] under this
Section 9.3.2.3 [**]with this Section 9.3.2.3 shall not be deemed a material
breach of this Agreement and Agilent shall not have the right to terminate this
Agreement as a result of such disclosure under Section 13.2(a) or 13.2(c),
provided that Customer has complied with the terms set forth in this Section
9.3.2.3.

 

9.3.2.4              Customer shall not disclose any Agilent Know-How, or any
Third Party Know-How disclosed to Customer under the Confidentiality Agreement,
to any Third Party without obtaining Agilent’s express prior written consent to
such disclosure. [**].

 

9.3.2.5              Notwithstanding any other provision herein, Customer shall
not [**] shall not be unreasonably withheld or delayed.  In the event that
Customer is [**].

 

9.4                                  Reservation of Rights.  Except as expressly
provided herein, no license to any Agilent Intellectual Property or Customer
Intellectual Property is granted, conveyed or implied.  For the avoidance of
doubt, no license to any Agilent Know-How owned, licensed or developed by or on
behalf of Agilent is granted, conveyed or implied except pursuant to the license
granted to Customer under Section 9.3.2.3.  All rights not conferred are
expressly reserved.

 

9.5                               Subcontracting.  Agilent shall only engage
those Affiliates and Third Parties approved by Customer in writing to
manufacture the Product and shall not sub-license the rights under any Customer
Intellectual Property other than to such approved Affiliates and Third Parties
and solely for the purpose of manufacturing and supplying Product to Customer.

 

9.6                               Disclosure of Process Patents, Process
Overview and Know-How.

 

9.6.1                        Disclosure of Process Patents.  All Patents owned
or licensed by Agilent that cover or claim the Process are set forth in Exhibit
F.  During the Term, upon the reasonable request of Customer, no more than [**],
Agilent shall update Exhibit F.  Agilent shall not incorporate into the Process
any Patents unless the Parties have agreed to incorporate such Patents into the
Process pursuant to the Change Management process.

 

9.6.2                        Disclosure of Process Overview.  An overview of the
Process is attached to this Agreement as Exhibit H.  Agilent acknowledges and
agrees that Exhibit H does not contain any Agilent Proprietary Information and
that Customer may disclose Exhibit H, or any information contained therein, to
any Third Party to the extent such Third Party has a reasonable need to know
such information.

 

9.6.3                        Third Party Know-How.  Agilent has not and shall
not incorporate into the Process any Third Party Know-How unless (A) Agilent has
the right to sublicense such Third Party Know-How to Customer in accordance with
Section 9.3.2.3 and (B) the Parties have agreed to incorporate such Third Party
Know-How into the Process pursuant to the Change Management process.  In
addition, Agilent shall not disclose to Customer any Third Party Know-How unless
(A) Agilent has the right to sublicense such Third Party Know-How to Customer in
accordance with Section 9.3.2.3 and (B) prior to such disclosure, Agilent
notifies Customer that such Know-How is Third Party Know-How.  In the event that
the Parties agree to incorporate Third Party Know-How into the Process under
this Section 9.6.3, any license granted to Customer under Section 9.3.2.3 shall
include such Third Party Know-How.

 

9.7                               Licenses to Use the Process.  Agilent is
responsible for the procurement of any licenses to Intellectual Property
necessary to use the Process to manufacture the Product under this Agreement.
 Agilent shall have full responsibility for the determination of whether and
from

 

14

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which Third Party it requires any such license to Intellectual Property claiming
or covering the Process for the manufacture of the Product under this Agreement
and for the procurement of any such license.  For purposes of clarity, nothing
in this Section 9.7 shall limit or prevent Customer, in its sole discretion,
from obtaining any license or other rights to any Third Party Intellectual
Property necessary or useful to manufacture the Product.

 

9.8                               Third Party Infringement Claims.  Agilent will
defend or settle any Third Party claim against Customer, its officers, directors
and employees, that Agilent’s use of the Process to manufacture the Product
under this Agreement infringes the Third Party’s Intellectual Property rights.
The Parties shall comply with the indemnification process set forth in Section
10.3 with respect to any such Third Party claims.  Agilent will pay infringement
defense costs, settlement amounts and court awarded damages.  Agilent shall have
no obligation under this Section 9.8 for any claim of infringement arising from
Product use prohibited by this Agreement.  This Section 9.8 states Customer’s
sole and exclusive remedy with respect to any such Third Party claim.

 

10.                               INDEMNITIES AND INSURANCE

 

10.1                        Agilent’s Indemnity Obligations.  Agilent will
indemnify, defend and hold harmless Customer, its officers, directors and
employees, from and against any and all claims, losses, damages, demands,
expenses or other liability arising out of a Third Party claim to the extent
caused by (i) failure of the Product to conform to the Specification at the time
of delivery to Customer’s carrier; or (ii) the gross negligence or willful
misconduct of Agilent.  Agilent’s obligations  under this Section 10.1 do not
apply with respect to any claim subject to indemnification under Section 10.2.

 

10.2                        Customer’s Indemnity Obligations.  Customer will
indemnify, defend and hold harmless Agilent, its officers, directors and
employees, from and against any and all claims, losses, damages, demands,
expenses or other liability arising out of a Third Party claim to the extent (i)
arising from the sale, marketing or distribution of the Product or Finished
Product, or use of the Product or Finished Product by Customer or any Third
Party including death or injury to any person; or (ii) caused by the gross 
negligence or willful misconduct of Customer.  Customer’s obligations under this
Section 10.2 do not apply with respect to any claim subject to indemnification
under Section 10.1.

 

10.3                        Process.  Each Party agrees to notify the other
Party promptly upon receipt of any claim for which indemnification is sought. 
The Party seeking indemnification will provide the indemnifying Party with such
information and assistance as the indemnifying Party may reasonably request, at
the expense of the indemnifying Party.  In no event may either Party compromise
or settle any claim or suit in a manner that admits fault or negligence on the
part of the other Party (or any indemnitee) without the prior written consent of
the other Party, which consent shall not be unreasonably withheld.  The
indemnifying party shall have no liability under this Article 10 with respect to
claims or suits settled or compromised by the indemnified party without the
indemnifying party’s prior written consent.  The indemnified Party may, at its
own expense, participate in the defense of any claim.  In the event that the
indemnifying Party fails to assume control of the defense of any claim, the
indemnified Party may assume control at the expense of the indemnifying Party.

 

10.4                        Insurance.  During the term of this Agreement,
Agilent will maintain insurance coverage in accordance with the Memorandum of
Insurance attached hereto as Exhibit D.

 

11.                               COMPLIANCE WITH LAWS AND REGULATORY MATTERS

 

11.1                        Compliance with Laws.  Each Party shall comply with
all applicable laws and regulations governing the performance of such Party’s
obligations under this Agreement.  Without limiting

 

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the foregoing, Agilent shall ensure that the Facility conforms to GMP and the
requirements of all applicable Regulatory Authorities.

 

11.2                        Regulatory Filings.  Customer, at its expense, shall
be solely responsible for the preparation, filing and maintenance of all
regulatory documents and all governmental permits, licenses and other approvals
as may be necessary with respect to the formulation, marketing, distribution
sale and use of the Product and Finished Product.  Upon Agilent’s request,
Customer will provide Agilent with a copy of all regulatory documents relating
to the manufacture of Product under this Agreement.

 

11.3                        Use Restrictions.  Notwithstanding any other
provision of this Agreement, Customer acknowledges and agrees that the Product
manufactured by Agilent and supplied to Customer under this Agreement (i) is not
intended for commercial use and (ii) shall not be used for commercial purposes. 
For avoidance of doubt, validation Batches shall be manufactured and supplied to
Customer under the Commercial Supply Agreement.

 

11.4                        Permits.  Agilent at its expense shall be solely
responsible for, and has the obligation to prepare, file and maintain all
licenses, permits and approvals as may be necessary with respect to the
manufacture of the Product at the Facility, including all regulatory approvals
required to import raw materials and packaging components.

 

11.5                        Export Controls.   Each Party shall comply with
applicable US and other laws, rules and regulations that govern the import,
export and re-export of the Product, including the U.S. Export Administration
Regulations, and will obtain any required export and import authorizations.

 

11.6                        Record Retention.  Agilent shall maintain the
records and documentation relating to the manufacture of the Product in
accordance with ICH guidance, Agilent’s Standard Operating Procedure and the
Quality Agreement.

 

11.7                        Technical Support.

 

11.7.1                 Upon notification to Agilent that Customer has received a
complaint or inquiry regarding the safety, efficacy or quality of the Product or
Finished Product, Agilent shall, within a reasonable period, supply Customer
with a chemical analysis of a number of retained samples, maintained in
accordance with the Quality Agreement, of the Batch(es) of the Product in
question.

 

11.7.2                 Upon notification to Customer that Agilent has received a
complaint or inquiry regarding or discovery by Customer of any issues relating
to the safety, efficacy or quality of the Product or Finished Product, Customer
shall, within a reasonable period, provide technical support as reasonably
requested by Agilent, which may include, but shall not be limited to, technical
advice and chemical analysis of retained samples of the Product, maintained in
accordance with the Quality Agreement.

 

11.7.3                 All technical support provided by Agilent under this
Section 11.7 shall subject to the pricing and payment terms for technical and
regulatory support as set forth in the Statement of Work.

 

11.8                           Regulatory Support.

 

11.8.1                 Agilent agrees to cooperate with, and provide regulatory
assistance to, Customer to support existing, pending or new Product or Finished
Product registrations and marketing approvals, in each case, with any relevant
governmental authority.  The foregoing assistance rendered by Agilent may
include: (i) assisting Customer in completing and submitting changes to any
regulatory submissions related to the Product; (ii) cooperation in connection
with pre-approval inspections carried out by governmental

 

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authorities; and (iii) providing information to Customer that may be required by
a relevant governmental authority to support the Product or Finished Product,
including the manufacturing and exportation related thereto.  All regulatory
support provided by Agilent under this Section 11.8 shall be subject to the
pricing and payment terms for technical and regulatory support as set forth in
the Statement of Work.

 

11.9                           FDA Debarment Statement.  Agilent hereby
certifies that neither Agilent nor any employee engaged by Agilent to perform
services under this Agreement has been debarred under section 306 of the Federal
Food, Drug and Cosmetic Act in connection with the performance of services under
this Agreement or any comparable law or regulation outside of the United
States.  In the event that Agilent becomes aware of any such debarment, Agilent
will provide Customer with written notice thereof.   Agilent will request that
all GMP manufacturing and testing subcontractors utilized pursuant to Section
2.4 of the Quality Agreement provide Customer with a certification that is
substantially similar to the certification provided by Agilent in this Section
11.9.   In the event that any such subcontractor fails to provide the
certification, Customer may withdraw its approval for such subcontractor and
Agilent shall cease using such subcontractor to provide services under this
Agreement.

 

12.                               FORCE MAJEURE

 

Neither Party will be liable for any failure or delay in performance of its
obligations under this Agreement to the extent such failure or delay is caused
by any event beyond such Party’s reasonable control, including fire, flood,
explosion, unavailability of utilities or raw materials, labor difficulties,
war, riot, act of God, export control regulation, or other laws or regulations,
action or failure to act of any governmental authority, or any judgment,
injunction or order of a court, administrative agency or regulatory authority
having the effect of preventing or adversely affecting either Party’s
performance under this Agreement.

 

13.                               TERM AND TERMINATION

 

13.1                           Term.  Unless otherwise terminated under this
Article 13, this Agreement will commence as of the Effective Date and will
continue for five (5) years (the “Initial Term”).  Unless otherwise terminated
in accordance with this Article 13, this Agreement shall be automatically
extended for an indefinite period (the “Renewal Term” and together with the
Initial Term, the “Term”).  Notwithstanding any of the foregoing, either Party
may terminate this Agreement at the end of the Initial Term or during the
Renewal Term provided, however, that it has given the other Party at least
eighteen (18) months prior written notice of termination.

 

13.2                           Termination.

 

(a) This Agreement or a Statement of Work may be terminated by either Party upon
[**] days written notice in the event of a material breach of any provision of
this Agreement or such Statement of Work; provided, however, that the breaching
Party will have an opportunity to (i) cure the breach during the [**], or (ii)
provide the non-breaching Party with a plan to remedy the breach within the
[**], and if so cured, no termination will be deemed to have occurred as long as
the breaching Party diligently pursues the plan to remedy the breach and
completes such plan in accordance with the time frame mutually agreed to by the
Parties (such time frame not to exceed an additional [**] days); or

 

(b) This Agreement may be terminated by either Party immediately upon written
notice to the other Party (i) if the other Party makes an assignment for the
benefit of creditors; (ii) if proceedings in voluntary or involuntary bankruptcy
are initiated by, on behalf of or against the other Party (and, in the case of
any such involuntary proceeding, not dismissed within ninety (90) days); (iii)
if the other Party is adjudicated bankrupt, files a petition under insolvency
laws, is dissolved or has a receiver appointed for substantially all of its
property; or (iv) if the other Party

 

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ceases operation of its business as its business has normally been conducted, or
terminates substantially all of its employees.

 

(c)    In the event of either Party’s material breach of its confidentiality
obligations under Article 14 with respect to trade secrets of the disclosing
Party which have been specifically identified as such in writing by the
disclosing Party, the Parties shall refer the matter for resolution under the
escalated dispute resolution process set forth in Section 16(b).  In the event
that the Parties are unable to resolve the matter following the dispute
resolution process set forth in Section 16(b), then the non-breaching Party may
terminate this Agreement upon written notice to the breaching Party.  For the
avoidance of doubt, [**].

 

(d) This Agreement or a Statement of Work may be terminated by Customer, with or
without cause, upon twelve (12) months prior written notice to Agilent.

 

(e) In the event that Customer fails, under this Agreement or under the
Commercial Supply Agreement, for a period of thirty-six (36) months (i) to place
a Purchase Order for a minimum of one hundred (100) oligonucleotide grams of
Product and (ii) to take delivery of such Product  within the lead times as set
forth in Section 4.3.1 of this Agreement or within the lead times as set forth
in the Commercial Supply Agreement, Agilent shall have the right to terminate
this Agreement upon written notice to Customer without further opportunity to
cure.

 

13.3                           Effect of Termination or Expiration.

 

13.3.1                 Section 3.5.1 shall survive termination or expiration of
this Agreement unless terminated by Agilent pursuant to Section 13.2(a), (b),
(c) or (e), or by Customer pursuant to Section 13.1 or 13.2(d).  If this
Agreement is terminated by Customer pursuant to Section 13.2(a), (b) or (c), the
obligations under Section 3.5.1 shall survive such termination for a period of
five (5) years after the effective date of such termination, regardless of
whether the Commercial Supply Agreement is in effect.

 

13.3.2                 Termination or expiration of this Agreement or any SOW
shall not release either Party from any liability, right of action or other
obligation which has arisen prior to such termination or expiration including
Agilent’s obligation to deliver to Customer such quantity of Product under any
accepted Purchase Order by Agilent prior to the effective date of termination or
expiration, and Customer’s obligation to pay Agilent the amount set forth in
such Purchase Order.  In addition, in the event of termination of any SOW under
Section 13.2, Customer shall pay Agilent for all work performed under such SOW
prior to the termination date.

 

13.4                           Surviving Provisions.  Notwithstanding any
expiration or termination of this Agreement, the following provisions shall
survive:  6.2, 6.3, 7, 8.2.3, 8.2.6, 9, 10, 11, 12, 13, 14, 15 and 16.

 

14.                               CONFIDENTIAL INFORMATION

 

14.1                           Proprietary Information. The terms and conditions
of Confidentiality Agreement dated March 22, 2011, by and between Customer and
Agilent (“Confidentiality Agreement”), attached hereto as Exhibit G and
incorporated herein by this reference.  Capitalized terms used in this Article
14 and not defined in this Agreement shall have the meanings ascribed to them in
the Confidentiality Agreement.  The terms and conditions of the Confidentiality
Agreement shall apply to information exchanged under this Agreement; provided
that:

 

14.1.1                 with respect to information exchanged pursuant to this
Agreement, the “Purposes” as defined in Section 1 of the Confidentiality
Agreement shall be amended to mean the conduct of activities and exercise of
rights granted pursuant to this Agreement;

 

18

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

 

 

14.1.2                 notwithstanding Section 3 of the Confidentiality
Agreement, the Confidentiality Agreement shall apply to all Proprietary
Information disclosed between the Parties pursuant to the Confidentiality
Agreement and/or this Agreement from March 22, 2011 until the end of the Term;

 

14.1.3                 notwithstanding Section 8(c) of the Confidentiality
Agreement, as it applies to information exchanged under this Agreement, shall be
construed and interpreted in accordance with the laws of the State of New York
as provided in Section 16(k);

 

14.1.4                 notwithstanding Section 8(e) of the Confidentiality
Agreement, the obligations of confidentiality and non-use under the
Confidentiality Agreement shall apply until the [**] anniversary of the
expiration or termination of this Agreement;

 

14.1.5                 the restrictions on disclosure and use set forth in the
Confidentiality Agreement shall not apply to the disclosure of this Agreement or
the disclosure of Proprietary Information to governmental authorities (i) that
is required by applicable law or regulation to be submitted by Customer in
connection with the issuance or maintenance of marketing approvals for the
Product or Finished Product; (ii) that is submitted by either Party to comply
with requests for information from any governmental authority; or (iii) that is
submitted by either Party to comply with applicable governmental regulations
(including the rules and regulations of any stock exchange); provided that, (x)
to the extent permitted by applicable law, Customer or Agilent, as the case may
be, will give reasonable advance notice to the other Party of such disclosure
requirement in order to allow the other Party the opportunity to seek
appropriate legal relief to prevent or limit disclosure of its Proprietary
Information; (y) reasonable measures shall have been taken by the Party seeking
to disclose the other Party’s Proprietary Information to ensure confidential
treatment of such Proprietary Information;  and (z) any disclosure shall be
limited to such portion of the other Party’s Proprietary Information that is
legally required to be disclosed.

 

14.1.6                 notwithstanding anything to the contrary in the
Confidentiality Agreement, but subject to Section 14.1.1, in the event that the
Recipient wishes to disclose this Agreement or the Disclosing Party’s
Proprietary Information to actual or potential investors, lenders, acquirers,
merger partners, or professional advisors who have a reasonable need to know
such information, the Recipient shall provide prior written notice thereof to
the Disclosing Party, and the Parties shall promptly meet (in person or via
telephone) and confer prior to any such disclosure for the purpose of avoiding
any inappropriate disclosure of the Disclosing Party’s Proprietary Information. 
Following such meeting, if the Disclosing Party has provided its express prior
written consent to such disclosure, which consent shall not be unreasonably
withheld or delayed, the Recipient may disclose the Disclosing Party’s
Proprietary Information to such Third Party; provided that (i) the Recipient
shall only disclose such amount of the Disclosing Party’s Proprietary
Information as is reasonably necessary; and (ii) the Recipient has entered into
a confidentiality agreement, with terms of confidentiality at least as
restrictive as the terms and conditions set forth in this Article 14 and the
Confidentiality Agreement, with such Third Party (other than attorneys and
accountants of Recipient who are bound to confidentiality under applicable
ethical and professional rules) before disclosing any of the Disclosing Party’s
Proprietary Information.   In the event that the Disclosing Party has not
consented to such disclosure, the Recipient may engage an independent Third
Party consultant reasonably acceptable to the Disclosing Party and subject to
confidentiality obligations at least as restrictive as the terms and conditions
set forth in this Article 14 and the Confidentiality Agreement, to evaluate the
Parties’ rights and obligations hereunder and such independent Third Party
consultant shall be permitted to

 

19

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

 

disclose to such Third Party confirmation solely regarding the adequacy of such
rights and obligations and the performance hereunder.  For the avoidance of
doubt, the independent Third Party consultant shall not be permitted to disclose
any Proprietary Information of the Disclosing Party to any Third Party.  The
Parties agree that the process set forth in this Section 14.1.6 shall not apply
to Customer’s use or exercise of the license rights under Sections 9.3.2.1,
9.3.2.2 or 9.3.2.3, provided that Customer complies with the provisions of the
applicable Sections 9.3.2.1, 9.3.2.2 or 9.3.2.3.  In addition, in the event that
Customer exercises the license rights under Section 9.3.2.3, the Parties further
agree that the process set forth in this Section 14.1.6 shall continue to apply
prior to disclosure of this Agreement or any Proprietary Information to any
actual or potential investor, lender, acquirer, merger partner or professional
advisor.

 

14.2                           Remedies.  Each Party shall be entitled, in
addition to any other right or remedy it may have, at law, in equity or under
this Agreement, to seek temporary, preliminary and permanent injunctions,
enjoining or restraining the other Party and its Affiliates from any violation
or threatened violation of this Article 14.

 

15.                               LIMITATION OF LIABILITY

 

15.1                           EXCEPT IN CONNECTION WITH (A) A BREACH OF ARTICLE
14 AND (B) ARTICLE 10, IN NO EVENT WILL EITHER PARTY OR ITS AFFILIATES,
SUBCONTRACTORS OR SUPPLIERS BE LIABLE FOR ANY INDIRECT, INCIDENTAL, SPECIAL OR
CONSEQUENTIAL DAMAGES (INCLUDING LOST PROFITS, LOST DATA, OR LOSS OF USE)
ARISING OUT OF THIS AGREEMENT, INCLUDING ANY PRODUCT OR SERVICE PROVIDED UNDER
THIS AGREEMENT OR THE USE THEREOF, ANY PERFORMANCE, OR FAILURE TO PERFORM UNDER
THIS AGREEMENT, REGARDLESS OF WHETHER SUCH DAMAGES ARE BASED ON TORT, WARRANTY,
CONTRACT OR ANY OTHER LEGAL THEORY, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH
DAMAGES.  THIS EXCLUSION IS INDEPENDENT OF ANY OTHER REMEDY SET FORTH IN THIS
AGREEMENT.  NOTWITHSTANDING THE FOREGOING, AGILENT SHALL PAY ALL SETTLEMENT
AMOUNTS AND COURT AWARDED DAMAGES IN ACCORDANCE WITH SECTION 9.8, PROVIDED THAT
THE PARTIES HAVE COMPLIED WITH THE INDEMNIFICATION PROCESS SET FORTH IN SECTION
10.3.

 

15.2                           EXCEPT IN CONNECTION WITH (A) A BREACH OF ARTICLE
14; (B) THIRD PARTY CLAIMS UNDER SECTION 9.8; AND (C) DAMAGES CAUSED BY
AGILENT’S GROSS NEGLIGENCE OR WILLFUL MISCONDUCT, TO THE FULLEST EXTENT
PERMITTED BY LAW, AGILENT’S LIABILITY TO CUSTOMER UNDER THIS AGREEMENT IS
LIMITED TO THE AGGREGATE AMOUNTS PAID BY CUSTOMER TO AGILENT  IN RESPECT OF THE
RELEVANT BATCH FROM WHICH THE CLAIM AROSE.

 

15.3                           NOTWITHSTANDING ANY OTHER PROVISION OF THIS
AGREEMENT, IN NO EVENT SHALL AGILENT BE LIABLE FOR ANY COSTS WHATSOEVER TO
PROCURE, SUPPLY OR REPLACE PEG, REGARDLESS OF WHETHER SUCH COSTS ARE BASED ON
TORT, CONTRACT, WARRANTY, LATENT DEFECT, INDEMNITY OBLIGATIONS OR ANY OTHER
LEGAL THEORY, EXCEPT TO THE EXTENT THAT SUCH COSTS ARE SOLELY AND DIRECTLY
CAUSED BY AGILENT’S GROSS NEGLIGENCE OR WILLFUL MISCONDUCT.

 

16.                               MISCELLANEOUS

 

a.              Notices.  All notices required or permitted to be given under
this Agreement must be in writing and delivered to the other Party as set forth
below.  Notices are validly given upon the earlier of confirmed receipt by the
receiving Party or three (3) days after dispatch by a reputable courier or

 

20

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

 

certified mail, return receipt requested.  Either Party may change its
designated contact and address for purposes of notice by giving notice to the
other Party in accordance with these provisions.

 

Agilent Technologies, Inc.

Ophthotech Corporation

5555 Airport Blvd.

214 Carnegie Center

Suite 100

Suite 302

Boulder, CO 80301

Princeton, NJ 08540

Attn: General Manager

Attn: Chief Business Officer

 

 

With a copy to:

 

 

 

Agilent Technologies, Inc.

Ophthotech Corporation

5301 Stevens Creek Blvd.

One Penn Center, 19th Floor

Santa Clara CA 95051

New York, NY 10119

Attn: General Counsel

Attn: General Counsel

 

b.              Escalated Dispute Resolution.  In the event that the Parties are
unable to agree upon any disputes arising under this Agreement, including
without limitation any claims of breach that may give rise to termination, the
Parties’ relationship managers agree to negotiate in good faith to resolve any
such disputes.  If such negotiations and meetings do not resolve the dispute
within [**] days after notice of the dispute, then a senior executive from each
Party will meet face to face within [**] days or as mutually agreed between them
to attempt to resolve such dispute.  If the dispute is not resolved to the
satisfaction of these executives within [**] days, then either Party may pursue
all available legal remedies.  Notwithstanding the foregoing, either Party may
seek injunctive relief with respect to any disputed matter without following the
dispute resolution procedure set forth above.

 

c.               Exhibits.  The following Exhibits attached to this Agreement
are deemed a part of this Agreement and incorporated by reference herein:

 

EXHIBIT A          PRODUCT

 

EXHIBIT B          INITIAL ORDERS

 

EXHIBIT C          QUALITY AGREEMENT

 

EXHIBIT D          MEMORANDUM OF INSURANCE

 

EXHIBIT E          STATEMENTS OF WORK

 

EXHIBIT F           LIST OF PATENTS

 

EXHIBIT G          CONFIDENTIALITY AGREEMENT

 

EXHIBIT H          PROCESS OVERVIEW

 

EXHIBIT I           COMMERCIAL SUPPLY AGREEMENT TERMS

 

EXHIBIT J           PRICING

 

d.              Independent Contractors.  The relationship of the Parties
established under this Agreement is that of independent contractors and neither
Party is a partner, employee, agent or joint venturer of or with the other.

 

21

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

 

e.               Assignment.   Except as otherwise provided in this Section
16(e), neither this Agreement nor any part hereof may be assigned or transferred
by either Party, whether by operation of law or otherwise, without the other
Party’s prior written consent.  Either Party shall have the right to assign this
Agreement, without the other Party’s consent, in the event of a sale or transfer
of the business as to which this Agreement relates, whether such sale or
transfer occurs by merger, reorganization, asset and/or stock purchase, or by
any other means, provided that the assignee agrees in writing to assume all of
the assignor’s obligations under this Agreement.  The assigning Party shall
notify the non-assigning Party in writing as soon as possible of any sale or
transfer of its business.  Any assignment or purported assignment in violation
hereof shall be void.  This Agreement will be binding upon and inure to the
benefit of the Parties and their permitted successors and assigns.

 

f.                Headings; Construction; Interpretation.  Headings used herein
are for convenience only and shall not in any way affect the construction of or
be taken into consideration in interpreting this Agreement.  The terms of this
Agreement represent the results of negotiations between the Parties and their
representatives, each of which has been represented by counsel of its own
choosing, and neither of which has acted under duress or compulsion, whether
legal, economic or otherwise.  Accordingly, the terms of this Agreement shall be
interpreted and construed in accordance with their usual and customary meanings,
and each of the Parties hereto hereby waives the application in connection with
the interpretation and construction of this Agreement of any rule of law to the
effect that ambiguous or conflicting terms or provisions contained in this
Agreement shall be interpreted or construed against the Party whose attorney
prepared the executed draft or any earlier draft of this Agreement.  Any
reference in this Agreement to an Article, Section, subsection, paragraph,
clause or Exhibit shall be deemed to be a reference to any Article, Section,
subsection, paragraph, clause or Exhibit, of or to, as the case may be, this
Agreement.  Except where the context otherwise requires, (i) any definition of
or reference to any agreement, instrument or other document refers to such
agreement, instrument other document as from time to time amended, supplemented
or otherwise modified (subject to any restrictions on such amendments,
supplements or modifications set forth herein or therein); (ii) any reference to
any law refers to such law as from time to time enacted, repealed or amended;
(iii) the words “herein,” “hereof” and “hereunder,” and words of similar import,
refer to this Agreement in its entirety and not to any particular provision
hereof; (iv) the words “include,” “includes,” “including,” “exclude,”
“excludes,” and “excluding,” shall be deemed to be followed by the phrase “but
not limited to,” “without limitation” or words of similar import; and (v) all
references in this Agreement to “days” will, unless otherwise specified herein,
mean calendar days.

 

g.               No Third Party Beneficiaries.  No provisions of this Agreement
are intended to confer or give, or will be construed to confer or give, to any
person or entity other than Agilent and Customer any rights, remedies or other
benefits under or by reason of this Agreement.

 

h.              Severability.  If any provision of this Agreement is determined
by a court of competent jurisdiction to be invalid or unenforceable in any
respect, such determination will not impair or affect the validity, legality or
enforceability of the remaining provisions hereof, and each provision is hereby
declared to be separate, severable and distinct.  To the extent that any such
provision is found to be invalid, illegal or unenforceable, the Parties will
negotiate in good faith to substitute for such provision, to the extent
possible, a new provision that most nearly effects the Parties’ original intent
in entering into this Agreement or to provide an equitable adjustment in the
event no such provision can be added.  The other provisions of this Agreement
will remain in full force and effect.

 

i.                  Hierarchy Of Documents.  Unless otherwise specifically
agreed to by the Parties, in the event of any conflict between the terms of this
Agreement and its Exhibits, and a Purchase Order, the order of precedence is as
follows: (i) the terms of this Agreement; (ii) its Exhibits; and (iii) the terms
of

 

22

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

 

the accepted Purchase Order.  The Parties acknowledge and agree that the
pre-printed provisions on any Purchase Order will be deemed deleted and of no
effect whatsoever.

 

j.                 Entire Agreement.  This Agreement constitutes the entire
agreement between the Parties with respect to the subject matter hereof and
supersedes all prior communications, representations or agreements, whether oral
or written.  No modifications, amendments, or waiver of any term, condition or
provision of this Agreement will be binding on either Party unless in writing
and signed by an authorized representative of each Party.

 

k.              Governing Law.  This Agreement is made under and will be
construed in accordance with the laws of New York without giving effect to that
jurisdiction’s choice of law rules.  The United Nations Convention on Contracts
for the International Sale of Goods will not apply to this Agreement or to
transactions processed under this Agreement.

 

l.                  Counterparts.  This Agreement may be executed in
counterparts each of which, when executed and delivered, shall be original, but
all such counterparts shall constitute one and the same document.  The Parties
agree that signatures transmitted via portable document format (PDF) shall be
deemed originals until originals replace such copies.

 

APPROVED AND AGREED TO:

 

 

 

 

 

 

 

 

 

 

 

 

 

AGILENT TECHNOLOGIES, INC.

 

OPHTHOTECH CORPORATION

 

 

 

 

 

 

 

 

 

 

By:

/s/ Nelson Thune

 

By:

/s/ Bruce Peacock

 

 

 

 

 

Typed Name:

Nelson Thune

 

Typed Name:

Bruce Peacock

 

 

 

 

 

Title:

General Manager

 

Title:

Chief Financial and Business Officer

 

 

 

 

 

Date:

02 May 2014

 

Date:

May 2, 2014

 

23

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

 

EXHIBIT A

 

PRODUCT

 

Fovista (pegpleranib sodium, X01E)

 

[**].

 

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

 

EXHIBIT B

 

INITIAL ORDERS

 

Agilent

 

 

 

 

SOW/Document

 

 

 

 

Number

 

Date

 

Title

Q09-12-77

 

SEP 21, 2012

 

[**]

Q01-13-31

 

JAN 15, 2013

 

[**]

Q05-13-74C

 

JUL 18, 2013

 

[**]

Q08-13-110

 

SEP 20, 2013

 

[**]

 

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

 

 

OPHTHOTECH

 

Purchase order

PO#

001-0032.

 

PO Date:

12 Oct 2012

 

Phone:

[**]

 

Contact:

[**]

 

To:

Invoice & Ship To:

Agilent Technologies, Inc.

[**]

5555 Airport Blvd, Suite #100

Ophthotech Corp.

Boulder, CO 80301

5 Vaughn Drive, Suite 106

Attn: [**]

Princeton, NJ, 08540

Tel: [**]

Tel: [**]

Fax: [**]

Fax: [**]

 

Invoices submitted against this PO will be paid within [**] days of receipt.

 

Further to Agilent Quote # Q09-12-77, please supply and deliver the goods or
services below as described in the quote:

 

Item

 

Quantity

 

Description

 

Unit Price

 

Total Price

 

1

 

[**]

 

[**]

 

[**]

 

[**]

 

2

 

[**]

 

[**]

 

[**]

 

[**]

 

3

 

[**]

 

[**]

 

[**]

 

[**]

 

4

 

 

 

 

 

 

 

 

 

9

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Subtotal

 

$

[**]

 

 

 

 

 

 

 

Tax

 

 

 

 

 

 

 

 

 

Total

 

$

[**]

 

 

1.              Please send two copies of your invoice.

2.              Enter this order in accordance with the prices, terms, delivery
dates, and specifications listed above.

3.              Please notify us immediately if you are unable to ship/deliver
as specified.

 

Authorized Signature:

/s/ Bruce Peacock

 

Date

12 Oct 2012

 

 

 

 

 

Name:

Bruce Peacock

 

 

 

 

 

 

 

 

Title:

CBO

 

 

 

 

This order is not valid unless it is signed. Please acknowledge receipt of this
order.

 

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

 

OPHTHOTECH

 

Purchase order

PO#

001-0035

 

PO Date:

24Jan2013

 

Phone:

[**]

 

Contact:

[**]

 

To:

Invoice & Ship To:

Agilent Technologies, Inc.

[**]

5555 Airport Blvd, Suite #100

Ophthotech Corp.

Boulder, CO 80301

5 Vaughn Drive, Suite 106

Attn: [**]

Princeton, NJ, 08540

Tel: [**]

Tel: [**]

 

Fax: [**]

 

Invoices submitted against this PO will be paid within [**] days of receipt

 

Per Agilent Quote #: Q01-13-31 with the following exceptions
·              Release and In-process Specifications to be finalized
·              Any credit with regard to the expedite fee from Agilent Quote
Q09-12-77 to be discussed

 

Item

 

Quantity

 

Description

 

Unit Price

 

Total Price

 

1

 

[**]

 

[**]

 

[**]

 

[**]

 

2

 

 

 

 

 

 

 

 

 

3

 

 

 

 

 

 

 

 

 

4

 

 

 

 

 

 

 

 

 

5

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Subtotal

 

$

[**]

 

 

 

 

 

 

 

Tax

 

 

 

 

 

 

 

 

 

Total

 

$

[**]

 

 

1.              Please send two copies of your invoice.

2.              Enter this order in accordance with the prices, terms, delivery
dates, and specifications listed above.

3.              Please notify us immediately if you are unable to ship/deliver
as specified.

 

Authorized Signature:

/s/ Samir Patel

 

Date

24 Jan13

 

 

 

 

 

Name:

Samir Patel

 

 

 

 

 

 

 

 

Title:

CEO

 

 

 

 

This order is not valid unless it is signed. Please acknowledge receipt of this
order.

 

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

 

EXHIBIT C

 

QUALITY AGREEMENT

 

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

 

 

[g141821kg09i001.jpg]

[g141821kg09i002.gif]

 

Quality Agreement

 

Use as an exhibit to service and supply agreement

 

Customer:

Ophthotech Corporation

 

 

One Penn Plaza

 

 

New York, NY 10119

 

 

 

 

Supplier:

Agilent Technologies, Inc.

 

 

5555 Airport Boulevard

 

 

Boulder, Colorado 80301

 

 

 

 

Product(s):

E10030 (PEGylated oligonucleotide) CSN API

 

 

 

 

Services:

Laboratory Testing

 

 

· Manufacturing Support and Finished API Release and Stability (CTX)

 

 

· Finished Drug Product Release and Stability Testing (CTL)

 

 

 

 

Version:

00

 

 

Approvals:

 

/s/ Nelson Thune

 

11/4/13

Agilent Technologies General Manager

 

Date

 

 

 

 

 

 

/s/ illegible

 

06 Nov 13

Agilent Manufacturing

 

Date

 

 

 

 

 

 

/s/ Celeste O’Connor

 

08 Nov 13

Agilent Technologies Quality Assurance

 

Date

 

 

 

 

 

 

/s/ Douglas Brooks

 

06-Nov-2013

Ophthotech Manufacturing

 

Date

 

 

 

 

 

 

/s/ Douglas Kollmorgen

 

05-Nov-2013

Ophthotech Quality Assurance

 

Date

 

 

 

 

 

 

 

 

 

Other

 

Date

 

Ophthotech: QA-AGR-0001 V00

Agilent:        QA-CON-0021

CONFIDENTIAL

 

 

29

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

 

Sections: (aligned to May 2013 FDA DRAFT Guidance)

 

1.                                      Purpose and Scope

2.                                      Terms

2.1.                            (3) Definitions

2.2.                            (21) Audits and Inspections

2.3.                            (2) Roles and Communications

2.4.                            (19) Subcontracting

2.5.                            (17) Complaints, returns and recalls

2.6.                            (22) Quality Agreement Modifications

3.                                      Quality Dispute Resolution

4.                                      Responsibilities, including
communication mechanisms and contacts

4.1.                            (4) General Responsibilities

4.2.                            Quality Unit Responsibilities

4.3.                            Facilities and Equipment

4.3.1.                  (12) Facility

4.4.                            Materials Management

4.4.1.                  (8) Raw Materials

4.4.2.                  (18) Reprocessing and Reworking

4.5.                            Product Specific Terms

4.5.1.                  (10) Manufacturing

4.5.2.                  (11) Qualification and Validation

4.6.                            Laboratory Controls

4.6.1.                  (15) Reference Standards

4.6.2.                  (9) Specifications and Test Methods

4.6.3.                  (14) Samples

4.6.4.                  (16) Stability

4.6.5.                  (13) Packaging, Labeling, Testing and Release of GMP API

4.7.                            Documentation

4.7.1.                  (7) Documentation

4.7.2.                  (20) Regulatory Submission

5.                                      Change Control and Revisions

5.1.                            (5) Change Management

5.2.                            (6) Deviation Handling and OOS Investigation

6.                                      (23) Attachments

6.1.                            Contact Information

 

30

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

 

1.                                      Purpose and Scope

 

1.1.                            This Quality Agreement (“Agreement”) for the
clinical and commercial stage manufacturing of Active Pharmaceutical Ingredients
(API), and testing of API and Drug Product under Good Manufacturing Practice
(GMP) is being executed by and between:

 

·                  Ophthotech Corporation hereafter referred to as “Ophthotech”.

 

·                  And, Agilent Technologies, Inc. hereafter referred to as
“Agilent”.

 

1.2.                            Agilent and Ophthotech are parties to
Manufacturing and Supply Agreements as set forth in Attachment 2 (the “Supply
Agreements”), pursuant to which Agilent is to supply Ophthotech API and perform
certain Manufacturing and Laboratory Services with respect to API and Drug
Product. This Agreement will become effective as of the date of the last
signatory herein.

 

1.3.                            Agilent shall operate in accordance with GMP for
manufacturing of GMP APIs and the performance of Manufacturing and Laboratory
Services and such other applicable regulatory requirements as described in this
Agreement and the applicable Supply Agreement.  The purpose of this Agreement is
to clearly define the roles and responsibilities of Agilent and Ophthotech with
regard to quality and GMP compliance issues concerning the production of GMP API
molecules and the performance of certain Manufacturing and Laboratory Services,
including testing of API and Drug Product.

 

1.4.                            The scope of this Agreement includes GMP and
quality compliance associated with the clinical and commercial stage
manufacturing of GMP API molecules and the performance of certain Manufacturing
and Laboratory Services, including testing of API and Drug Product.

 

2.                                      Terms

 

2.1.                            (3) Definitions

 

2.1.1.                  Analytical (Test) Methods — Methods used for analytical
testing, including Standard Test Methods and Compendial Methods.

 

2.1.2.                  Active Pharmaceutical Ingredient (API),—Any substance or
mixture of substances intended to be used in the manufacture of a drug
(medicinal) product and that, when used in the production of a drug, becomes an
active ingredient of the Drug Product as defined in ICH Q 7.  Such substances
are intended to furnish pharmacological activity or other direct effect on the
diagnosis, cure mitigation, treatment, or prevention of disease or to affect the
structure and function of the body.

 

31

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

 

2.1.3.                  Approval — The term “Approval” is defined as concurrence
between Ophthotech and Agilent, as evidenced in writing and signed by both
companies’ Authorized Quality Representatives. In certain cases, Approvals may
be obtained electronically or verbally, followed by a written confirmation.

 

2.1.4.                  Authorized Quality Assurance Representative — An
individual named within this Agreement with the authority to resolve any
disputes or conflicts relating to this Agreement in a timely and equitable
manner and in compliance with all applicable quality and regulatory
requirements.

 

2.1.5.                  Batch — A specific quantity of material produced in a
process or series of processes that is expected to be homogeneous, within
specified limits, and that is produced by Agilent in the same cycle of
manufacture as defined by the applicable batch record and which shall be
packaged and released with a single release and lot number.

 

2.1.6.                  Batch Packet — Relevant documentation to be transferred
by Agilent to Ophthotech to support the release of a Batch. This packet
includes, but is not limited to, copies of:

 

2.1.6.1.                  Executed Batch Records

2.1.6.2.                  all Deviations, including proposed CAPA’s where
appropriate, associated with the manufactured API

2.1.6.3.                  OOS investigations associated with analysis of the API

2.1.6.4.                  In-process results

2.1.6.5.                  Certificate of Analysis (COA)

2.1.6.6.                  Certificate of Compliance (COC)

2.1.6.7.                  QA disposition

 

2.1.7.                  Batch Production Record — An accurate reproduction of a
Master Batch Record used as instruction for and documentation of production
activities.

 

2.1.8.                  CAPA-Corrective action, preventative action.

 

2.1.9.                  Certificate of Analysis (COA) — A document, signed by an
authorized representative of Agilent, describing (i) the Specification; (ii) the
testing methods applied to the API in order to verify compliance with the
Specification, and (iii) the results thereof.

 

2.1.10.           Certificate of Compliance (COC) — A document, signed by an
authorized quality assurance representative of Agilent, attesting that a
particular Batch was manufactured in accordance with cGMP, and the
Specification.  The Certificate of Compliance may be included

 

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within the Certificate of Analysis, or separately, if required by Ophthotech.

 

2.1.11.           cGMP or GMP — Current Good Manufacturing Practices pursuant to
(i) the U.S. Federal Food, Drug, and Cosmetic Act as amended (21 USC 301 et
seq.), (ii) relevant U.S. regulations found in Title 21 of the U.S. Code of
Federal Regulations (including but not limited to Parts 11, 210, 211, 600 and
610), (iii) Commission Directive 2003/94/EEC of 08 October 2003, (iv) the EC
Guide to Good Manufacturing Practice for Medicinal Licensed Products, including
respective guidance documents; (v) any comparable laws, rules or regulations of
other jurisdictions as mutually agreed to by Ophthotech and Agilent, as each may
be amended from time to time; and (vi) the relevant current International
Conference on Harmonization (ICH) guidance documents, including the ICH Guidance
Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients and
ICH Guidance Q11

 

2.1.12.           Controlled Documents - Paper or electronic documents that are
part of the quality system and contain data/information required by cGMPs. These
documents may also be referred to as GMP documents. Such documents must be
initiated and revised through document control and/or change control procedures.
Examples of controlled documents are: SOPs, analytical test methods,
specifications, batch records, validation protocols, forms, etc.

 

2.1.13.           Critical Raw Material — A material (starting materials,
reagents and solvents) whose intended use is in the production of intermediates
or APIs and whose attributes must be controlled within predetermined criteria to
ensure that the API meets its specification.

 

2.1.14.           Deviation —  A departure from written standard where any of
the following is true:  requires investigation and root cause analysis, has the
potential for product, process, or equipment impact, requires CAPA for
prevention of future recurrence, requires a Change Control, or presents a
potential non-conformance with a regulatory filing, specification, or validated
parameter, or requires customer notification.

 

2.1.15.           Disposition — The action of assigning a status of release,
quarantine, reject etc. to a material.

 

2.1.16.           Drug Product — The dosage form in the final immediate
packaging intended for human clinical or commercial use.

 

2.1.17.           Executed Batch Record — A completed Batch Production Record.

 

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2.1.18.           Intermediate- A material produced during steps of the
processing of an API that undergoes further molecular change or purification
before it becomes an API. Intermediates may or may not be isolated.

 

2.1.19.           Master Batch Record (MBR) — The document that defines the
manufacturing methods, materials, and other procedures, directions and controls
associated with the manufacture and testing of the API.

 

2.1.20.           Out-of-Specification (OOS) — A result derived from testing
that is valid but does not comply with the established specification.  In this
case, “result” is defined as the final reportable value as determined according
to the test method.  Such a reportable value may be comprised of multiple
individual determinations (i.e., replicates) as per the test method.  Only
reportable values are compared to specifications; therefore only a reportable
value may constitute an OOS.

 

2.1.21.           Product — Any a) API, or (b) Drug Product comprised of API, or
(c) intermediate(s) of (a) or (b), in each case as specified in the applicable
Scope.

 

2.1.22.           Qualified Supplier — A supplier who has met minimum approval
standards and been qualified by Agilent, to provide required items or services
that may impact API quality.

 

2.1.23.           Raw Material — A general term used to denote starting
materials, reagents, and solvents intended for use in the production of
intermediates or APIs.

 

2.1.24.           Regulatory Authority-means any competent authority of the US,
Europe, Japan, or other regulated region which regulates the manufacture of the
API in accordance with ICH guidelines.

 

2.1.25.           Significant Change — Any change that: has the potential to
(a) impact the quality, safety, identity, strength, efficacy, potency or purity
of the API; (b) impact the regulatory commitments and/or reporting requirements
of the API; (c) require re-qualification or re-validation of the process,
methods, reference standards approved by Ophthotech; and/or (d) result in
changing or modifying Ophthotech’s approved Specifications, test methods or any
document approved by Ophthotech.

 

2.1.26.           Significant Deviation — A deviation that has been shown to
adversely impact final API, stability study, drug product or a critical raw
material.

 

2.1.27.           Specification — The Specification for the Product as set forth
in the Statement of Work, which Specification may be amended from time to time
in accordance with this agreement.

 

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2.1.28.           Subcontractor - Any manufacturer, packager, or other API
support service provider who performs processing, packaging, or testing of an
API or any intermediate step of manufacture, or other API support service on
behalf of Agilent.

 

2.2.                            (21) Audit and Inspections

 

2.2.1.                  Agilent agrees to allow the FDA and any other Regulatory
Authority to conduct any inspection related to the manufacture of the API which
the FDA or such Regulatory Authority requires and Agilent agrees to reasonably
cooperate with the FDA or such Regulatory Authority in connection with such
inspection. Agilent agrees to promptly notify Ophthotech of any inspections or
actions by a Regulatory Authority which could potentially impact the production
or distribution of the GMP API; provided that Agilent shall provide notice to
Ophthotech of any such inspection or action that relates to the API or Product
testing within [**] hours.  Ophthotech may be present during any regulatory
inspections involving their Product.  Agilent agrees to provide Ophthotech
(i) copies of any report issued and notice of any regulatory actions resulting
from such inspections within [**] business days of any written action from such
Regulatory Authority and (ii) within [**] days after Agilent’s receipt of such
regulatory action, a plan to make corrective actions to remedy such regulatory
action (which plan Agilent shall promptly implement and diligently pursue).

 

2.2.2.                  Ophthotech reserves the right to conduct compliance
audits of Agilent’s records and relevant areas of the Agilent facility that are
involved in the production, testing, or storage of the API and Intermediates.
Agilent requires a minimum of [**] business day notice for compliance audits.
During audits, Agilent shall provide Ophthotech with all relevant documentation
for the sole purpose of assuring API quality and compliance with agreed-upon
manufacturing procedures.

 

2.2.3.                  Ophthotech is entitled to one routine on-site GMP audit
per [**] period provided active manufacturing occurs during this period. A
request for audit due to a specific issue (‘for-cause’ audit) may be conducted
at any time with a minimum of a [**] business day notice and must be focused
only on the subject of the ‘for-cause’ audit.

 

2.2.4.                  During an audit by Ophthotech, any non-conformances will
be noted and documented in a report issued by Ophthotech within ([**] business
days. Agilent will formally respond in writing within [**] business days
following receipt of the report [**].

 

2.2.5.                  Ophthotech reserves the right, at Ophthotech’s expense,
to conduct PAI readiness and mock audit exercises at Agilent.

 

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2.3.                            (2) Roles and Communication

 

2.3.1.                  Ophthotech and Agilent will each appoint a Primary
Contact for communications between the two parties and who will jointly be
responsible for the coordination and management of the project, including
communication of quality and regulatory matters pursuant to this Agreement.

 

2.3.2.                  Both primary contacts will be included on all
communications between Agilent and Ophthotech.  For verbal communications
regarding quality and regulatory matters, the initiating party will summarize
the discussion in a written record, which will then be distributed by the
respective primary contact.

 

2.3.3.                  Ophthotech and Agilent will each appoint an Authorized
Quality Assurance (QA) Representative who will serve as the primary contact for
quality related notifications between the two parties.

 

2.3.4.                  Responsible personnel are identified in Attachment
23.1.  Either party may change its Project Manager or Authorized Quality
Assurance Representative by providing the other party written notice and
Attachment 23.1 shall be updated to reflect any such change(s).

 

2.4.                            (19) Subcontracting

 

2.4.1.                  Agilent shall use approved subcontractors according to
internal procedures.  Agilent will not subcontract any activities related to the
GMP manufacturing or testing using non-approved subcontractors of API without
prior approval of Ophthotech.

 

2.4.2.                  Agilent shall ensure that any quality impacting changes
proposed at a subcontractor site utilized for Ophthotech testing are assessed
and Ophthotech notified prior to the change being made.

 

2.5.                            (17) Complaints, Returns, and Recalls

 

2.5.1.                  Customer Complaints - Agilent agrees to maintain
appropriate systems for documenting and investigating any customer complaints
associated with the GMP API.  Agilent will assist Ophthotech with
investigational work to resolve the complaint. Agilent will respond within one
business day for any serious or patient safety related API complaints. In the
case of an emergency Agilent will rely upon site procedures to respond.

 

2.5.2.                  GMP API Returns — Agilent will maintain records for
returned products including batch number, quantity and reason.

 

2.5.3.                  Recalls — Ophthotech will be responsible for the recall
of any marketed Drug Products. Agilent is responsible for notifying

 

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Ophthotech of any GMP API that is the subject of a recall.  During a Product
recall, withdrawal, or field correction, Agilent shall keep accurate drug
accountability and distribution records, fully cooperate with Ophthotech in
notifying customers, and conducting the necessary recall and investigational
activities.  Agilent shall provide assistance in the investigation reasonably
required to determine the cause and extent of the problem necessitating the
recall.

 

2.6.                            (22) Quality Agreement Revisions

 

2.6.1.                  Any revision to this Quality Agreement or any related
attachments must be approved in advance by both parties. Revisions will be
documented as written addendums that are attached to the original Quality
Agreement.  Each addendum will minimally be approved by the Primary Contact and
the Quality Assurance representatives from both companies.

 

2.6.2.                  The Quality Agreement shall be updated and will
minimally be approved by the Primary contact and the Quality Assurance
representatives from both companies at the initiation of Ophthotech every [**]
years.

 

3.                                      Quality Dispute Resolution

 

3.1.                            In the event of a dispute as to whether (i) the
Product has a Latent Defect or (ii) the Product was not in Good Condition at the
time of delivery, the parties shall follow the dispute resolution procedure set
forth the applicable Supply Agreement.  In the unlikely event a dispute arises
regarding any other issue affecting product quality that cannot be resolved, the
parties agree to resolve the dispute in the following manner.

 

3.1.1.                  The parties agree to establish the basis of the dispute
in writing within [**] days of the origin of the dispute.

 

3.1.2.                  The parties agree to the description content and detail
of the dispute by signing and dating the dispute description document.

 

3.1.3.                  The document is escalated to the next higher comparable
level in both organizations wherein parties from both companies are tasked with
resolving the dispute as written.

 

3.1.4.                  In the event the escalation does not resolve the dispute
the parties agree to follow the dispute resolution procedure set forth for
Escalated Dispute Resolutionin the applicable Supply Agreement.

 

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4.                                      Responsibilities, including
communication mechanisms and contacts

 

4.1.                            (4) General Responsibilities

 

4.1.1.                  Agilent agrees to manufacture, test, and deliver the GMP
API in accordance with cGMP and other applicable compliance standards.

 

4.1.2.                  Agilent agrees to test and perform stability studies on
either API or Drug Product as denoted in applicable Statements of Work.

 

4.1.3.                  Agilent agrees to maintain and operate under a quality
system consistent with US and EU cGMP, including maintaining standard operating
procedures (“SOPs”), training and root cause analysis and corrective &
preventive actions.

 

4.1.4.                  Agilent agrees to ensure that personnel involved in the
manufacture, testing and disposition of the GMP API have the education, training
and experience, or any combination thereof, to enable those persons to perform
their assigned responsibilities. Training extends to the particular operations
that the employee performs and to the applicable GMP’s as they relate to API and
Drug Product and the employee’s functions. Training records shall be maintained
by Agilent as required by GMP and made readily available for the personnel
working on API and Drug Product. All training relative to a specific task will
be completed prior to the initiation of the task. Training will be conducted
with sufficient frequency to assure familiarity with requirements applicable to
the position and function.  Agilent will ensure that any necessary GMP or
technical training has been performed and is documented.

 

4.2.                            Quality Unit Responsibilities

 

4.2.1.                  The quality unit shall have the responsibility and
authority to approve or reject all components, drug product containers,
closures, in-process materials, packaging material, labeling, and drug products,
and the authority to review production records to assure that no errors have
occurred or, if errors have occurred, that they have been fully investigated.
The responsibilities and procedures applicable to the quality unit shall be in
writing; and the written procedures shall be followed.

 

4.2.2.                  The quality unit shall be responsible to assure adequate
testing facilities are available and utilized for the testing of raw materials,
components, API containers, closures, packaging materials, in-process materials,
and drug products.

 

4.2.3.                  The quality unit shall have the responsibility for
approving or rejecting all procedures or specifications impacting on the
identity, strength, quality, and purity of the drug product.

 

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4.3.                            (12) Facilities and Equipment

 

4.3.1.                  Agilent will manufacture the Ophthotech API only at the
Agilent facility located at 5555 Airport Blvd. Boulder, CO 80301. (“Facility”)

 

4.3.2.                  All critical measuring and monitoring devices used in
processing equipment will be calibrated according to a pre-determined documented
schedule. As appropriate, calibrations will be conducted using standards that
are traceable to NIST or an appropriate, traceable standard.

 

4.3.3.                  All GMP manufacturing operations will occur in equipment
and facilities that are fully qualified per the Agilent Validation Master Plan
and are subject to formal maintenance, calibration, and cleaning procedures.

 

4.3.4.                  The facility will be maintained according to procedure
to ensure a state of compliance and maintain a validated state relative to the
manufacturing of GMP APIs and in the performance of Manufacturing and Laboratory
Services.

 

4.3.5.                  Any proposed change in the facility that has the
potential to impact the quality of the Ophthotech API will be communicated to
Ophthotech prior to the change being made.

 

4.4.                            Materials Management

 

4.4.1.                  (8) Raw Materials

 

4.4.1.1.                                It is the responsibility of Agilent to
handle procurement, delivery, inspection, testing and storage of raw materials
(including components) that are used to produce the GMP API except as specified
in 4.4.1.6.  Materials will be tested and/ or examined against approved
specifications.

 

4.4.1.2.                                Materials of animal origin will be
certified BSE/TSE free as per Agilent internal procedures.

 

4.4.1.3.                                All Critical Raw Material suppliers will
be qualified as appropriate to the stage of development and the regulatory
status of the GMP API as per Agilent internal procedures. Agilent will select
suppliers for non-critical raw materials and components in accordance with the
use and after assessment by Agilent Quality.

 

4.4.1.4.                                The testing procedures for the Critical
Raw Materials will be performed per compendial methods or other test methods
developed by Agilent if a compendial testing is not available or applicable.

 

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4.4.1.5.                                Agilent shall use only those suppliers
of Critical Raw Materials that have been approved by Agilent. If Ophthotech
requests a specific supplier that is not a current Agilent qualified supplier,
Agilent and Ophthotech will work together to qualify that supplier.

 

4.4.1.6.                                Except as otherwise agreed to by the
Parties in writing, if Ophthotech supplies material to Agilent for API
manufacture, it is Ophthotech’s responsibility to qualify that supplier and
provide qualification documentation to Agilent, including BSE/TSE certification
and such qualification and audit records as agreed to by the Parties.

 

4.4.1.7.                                Agilent will maintain a Supplier
Qualification program that may be assessed by Ophthotech during a quality audit.

 

4.4.1.8.                                Agilent will maintain samples of
Critical Raw Materials, API and finished Drug Product in accordance with ICHQ7.
All materials shall be handled and stored in accordance with the approved
specifications.

 

4.4.1.9.                                Under no circumstances shall any
materials which may present a potential hazard to the raw materials utilized in
API be stored in the Facility, or in proximity to the area where raw materials
utilized in API are maintained. If such materials are stored in the Facility,
the Parties must agree to their separation and segregation.

 

4.4.2.                  (18) Reprocessing and Reworking

 

4.4.2.1.                                If either Ophthotech or Agilent
determines that reprocessing or reworking of the GMP API is necessary due to
OOS, manufacturing deviation, unmet Specifications, or otherwise, the procedure
will be documented and approved by Agilent Chemical Development, Agilent
Manufacturing, Agilent QA  and Ophthotech QA, provided that Agilent shall not
reprocess or rework the GMP API without the prior written consent of Ophthotech.

 

4.5.                            Product Specific Terms

 

4.5.1.                  (10) Manufacturing

 

4.5.1.1.                                Master Batch Record (MBR) - GMP APIs
will be manufactured in accordance with written MBRs that have been drafted by
Agilent and approved by Ophthotech.  MBRs will be reviewed and approved by the
Agilent QA

 

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department prior to use.  Executed Batch Records will be reviewed and approved
by the Agilent QA department prior to disposition to Ophthotech.

 

4.5.1.2.                                Waste Handling — Any waste generated by
the process will be disposed of according to Agilent procedures and in a secure
and legal manner which prevents unauthorized use and/or environmental compliance
problems.

 

4.5.2.                  (11) Qualification and Validation

 

4.5.2.1.                                Agilent will be responsible for the
qualification and validation of manufacturing and testing equipment and
processes, as mutually defined by Agilent and Ophthotech.

 

4.5.2.2.                                Agilent will perform qualification
and/or validation, when applicable, of any analytical test methods as required
by Ophthotech. Agilent will be responsible for generating protocols to
qualify/validate the test methods which will be reviewed and approved by both
Agilent and Ophthotech, if required.  Agilent will provide a final report to
Ophthotech for method transfer, qualification, and/or validation.

 

4.5.2.3.                                Agilent will not make a Significant
Change to any Ophthotech specific test method without prior approval from
Ophthotech. Compendial updates to methods are acceptable and will not require
Ophthotech pre-approval. Ophthotech will be notified of changes to generic
methods (other than compendial methods) used for the Ophthotech process and
copies provided on request.

 

4.5.2.4.                                Ophthotech is responsible for providing
Agilent with sufficient quantities of an appropriately qualified API reference
standard along with a reference standard qualification certificate or
appropriately tested reference material. Agilent can also be requested to
prepare an API reference standard as described in section 4.6.1.2

 

4.6.                            Laboratory Controls

 

4.6.1.                  (15) Reference Standards/ Materials

 

4.6.1.1.                                Any reference standards / materials that
are supplied by Ophthotech or obtained from an official source will be stored
and used in accordance with established Agilent procedures and any written
instructions provided by Ophthotech.

 

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4.6.1.2.                                Any reference standards/ materials
produced in-house at Agilent for Ophthotech will be appropriately documented and
tested to ensure appropriate characterization of the material.

 

4.6.1.3.                                (Copy of foregoing section) Ophthotech
is responsible for providing Agilent with sufficient quantities of an
appropriately qualified API reference standard along with a reference standard
qualification certificate or appropriately tested reference material. Agilent
can also be requested to prepare an API reference standard as described in
section 4.6.1.2

 

4.6.2.                  (9) Specifications and Test Methods

 

4.6.2.1.                                Agilent will follow written quality
system procedures for the identification, quarantine, handling, sampling,
testing and approval or rejection of materials. Agilent will perform testing per
established methods/procedures and review results against the Specifications. 
Changes to these methods and procedures will be consistent with the Change
Management section of this Agreement.  Deviations to the test methods and
procedures and OOS results will be handled in a manner consistent with the
Deviation and OOS sections of this agreement.

 

4.6.2.2.                                Critical Raw Materials — Agilent will
make recommendations for any change in Critical Raw Material Specifications and
test methods as necessary to assure quality and compliance. The establishment of
formal Critical Raw Material Specifications and test methods will occur per
Agilent’s internal procedures.

 

4.6.2.3.                                In-Process — Ophthotech and Agilent will
agree on in-process Specifications and test methods used during development.   
The establishment of in-process Specifications and test methods for validation
and commercial manufacturing will occur per Agilent’s internal procedures and
shall be subject to approval by Ophthotech.

 

4.6.2.4.                                Analytical Data Reporting Requirements -
Copies of all analytical QC raw data (including chromatograms) and reports
generated by Agilent will be provided to Ophthotech with the Batch Packet for
in-process and final API analysis following manufacture.  Copies of data related
to method transfer or validation will be available

 

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for on-site review by Ophthotech and provided to Ophthotech as required.

 

4.6.3.                  (14) Samples / Reserve

 

4.6.3.1.                                Raw Materials — Agilent agrees to sample
and retain sufficient amounts and stored under controlled conditions, of all
materials used in processing and testing, except water, compressed gasses and
any highly volatile compounds and compounds that are not stable. In addition to
the above, it is the responsibility of Agilent to retain Critical Raw Material
samples with appropriate labeling, storage and duration according to Agilent
procedures.

 

4.6.3.2.                                In-Process — Agilent will retain
in-process samples until the Batch has been approved for release or as requested
by Ophthotech in writing.

 

4.6.3.3.                                Final GMP API - Agilent will obtain
retain samples of the final GMP API in accordance as requested by Opthotech in
writing, but at a minimum, in sufficient amount to comply with ICH Q7 guidance
for API sample retains.  These retention samples will be packaged and stored in
accordance with ICH Q7 and the Agilent specification. Agilent will notify
Ophthotech prior to disposing of retain samples as per Agilent internal
procedures.

 

4.6.4.                  (16) Stability

 

4.6.4.1.                                Stability testing, both accelerated and
long-term, will be conducted as contracted by Ophthotech. Ophthotech will be
responsible for determining appropriate retest/expiry dates, storage conditions,
and packaging materials.

 

4.6.4.2.                                Stability testing will be conducted
under protocols written by Agilent and approved by Ophthotech and Agilent QA
prior to commencement of the stability study.

 

4.6.4.3.                                Both parties agree to inform the other
of the results of any stability testing for which they are responsible. This
includes notification of any stability results that are deemed OOS or
out-of-trend per established specifications and/ or Agilent internal procedures
per section 5.2 of this agreement.

 

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4.6.5.                  (13) Packaging, Labeling, Testing and Release of GMP API

 

4.6.5.1.                                The final packaging, labeling, and
testing of each GMP API Batch will be conducted in accordance with written
procedures, and with packaging and labeling requirements and test specifications
provided by Ophthotech.

 

4.6.5.2.                                Each batch will be internally released
by the Agilent QA department as per established internal procedures which will
include a review of associated batch records and analytical data.

 

4.6.5.3.                                A Certificate of Analysis (COA) will be
issued by Agilent for each Batch of API confirming that the API has been tested
in accordance with the Specification using approved methods. The COA will
contain results for all API analyses that have a Specification. Agilent will
provide an Analytical Data Report Form for any additional analyses not listed on
the Specification.

 

4.6.5.4.                                A Certificate of Compliance (COC) will
be issued by Agilent for each Batch of API confirming that the API has been
manufactured, packaged and tested in full compliance with GMP, ICH Q7 and local
Regulatory requirements. The COC will attest to the accuracy of the
manufacturing records and provide limited detail on the occurrence and
resolution of deviations that may have occurred during Batch processing and
testing. BSE/TSE certification for any animal derived raw materials, packaging
components and processing aids is also provided.

 

4.6.5.5.                                Final release authority for shipment of
each Batch of GMP API to Ophthotech will reside with Agilent’s QA department.

 

4.7.                            Documentation

 

4.7.1.                  (7) Documentation

 

4.7.2.                  The Agilent Primary Contact will provide and receive all
controlled documents to and from the Ophthotech Primary Contact.

 

4.7.3.                  Agilent will generate any internal Controlled Documents
necessary to support GMP API production and will be responsible for the
retention and storage of all Batch Packet documentation in a secure QA archive
according to Agilent’s record retention policy. Ophthotech shall be notified
prior to destruction of any Controlled Documents supporting a batch production
record and have the option of making

 

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arrangements for continued retention or the return of such documents to
Ophthotech.

 

4.7.4.                  A Certificate of Analysis (COA), Certificate of
Compliance (COC), BSE/ TSE Certification, and Material Safety Data Sheet or
Safety Data Sheet (MSDS/SDS) will be provided by Agilent with every GMP API
shipment.  Copies of completed Batch Packets documents will be provided to
Ophthotech as defined in Section (2).

 

4.7.5.                  Controlled Documents specific to the manufacture of
E10030 will be reviewed and approved by Ophthotech prior to Agilent making the
documents effective.

 

4.8.                            (20) Regulatory Interactions and Submissions

 

4.8.1.                  Regulatory Contacts. Unless otherwise required by
applicable law, Ophthotech will be solely responsible for all contacts and
communications with any regulatory authorities with respect to matters relating
to the API or any of the Manufacturing and Laboratory Services under a Statement
of Work. Agilent will notify Ophthotech immediately, and in no event later than
[**] days, after Agilent receives any contact or communication from any
regulatory authority relating in any way to the API or Product testing or the
Manufacturing and Laboratory Services under a Statement of Work and will provide
Ophthotech with copies of any such communication within [**] of receipt of such
communication by Agilent.  Agilent will consult with Ophthotech regarding the
response to any inquiry or observation from any regulatory authority relating in
any way to the API or Product testing or the Manufacturing and Laboratory
Services under a Statement of Work and will allow Ophthotech at Opthotech’s
discretion to participate in any further contacts or communications relating to
such Services.  Agilent will comply with all reasonable requests and take into
consideration all comments by Ophthotech with respect to all contacts and
communications with any regulatory authority relating in any way to the API the
Manufacturing and Laboratory Services under a Statement of Work.

 

4.8.2.                  Submissions. Agilent will provide to Ophthotech at
Ophthotech’s expense, input, data and written content regarding the
manufacturing and controls for the API as may be required for regulatory
submissions. As the drug sponsor, it is the responsibility of Ophthotech to
provide an appropriate template and specific content requests to Agilent.

 

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5.                                      Change Control and Revisions

 

5.1.                            (5) Change Management

 

5.1.1.                  Agilent will utilize a documented change control system
as defined by internal procedures to control changes to raw materials, packaging
materials, suppliers, equipment, manufacturing procedures, material
specifications, facilities, sampling procedures, analytical methods, a process
or method validated state or standard operating procedures.

 

5.1.2.                  Any Significant Change or other change  proposed by
Agilent to the MBR, Facility, Utilities, Equipment, Specifications and/or SOPs,
including but not limited to the manufacturing process, materials and/or
analytical methods which may affect the quality or performance of the API over
its shelf-life,  acceptance criteria not met for post-validation batches or
affect commitments made in regulatory filings (a) shall be made only as
permissible under the applicable Supply Agreement and this Quality Agreement;
and (b) must be approved by Ophthotech, in writing, prior to implementation for
routine production or release of any affected batch.

 

5.1.3.                  Ophthotech will use reasonable efforts to respond to any
written request for change from Agilent within [**] business days. If the change
request is part of an initiated manufacturing campaign, Ophthotech will use
reasonable efforts to respond within [**]. No Significant Change shall be
implemented by Agilent without the prior written approval of Ophthotech.

 

5.1.4.                  Ophthotech initiated requests for changes shall be
communicated to Agilent’s Quality management in writing using Ophthotech’s
change control documentation.  Agilent will use reasonable efforts to respond to
any written request for change from Ophthotech within [**] business days.  Such
Ophthotech requested changes shall, upon mutual agreement of the Parties, be
implemented by Agilent using Agilent’s current approved change management
procedures. Agilent shall not unreasonably withhold, condition or delay its
approval of any such change and any such changes required in order to comply
with applicable laws, rules or regulations shall not require such approval,
without reasonable justification.

 

5.2.                            (6) Deviation Handling and OOS Investigations

 

5.2.1.                  Any deviations from approved manufacturing, testing, or
storage procedures that occur in the course of batch production will be managed
according to Agilent’s internal procedures for deviation handling, and the
extent of investigation will be determined by Agilent and shall be commensurate
with the severity of the deviation and the potential API quality impact. Agilent
must notify Ophthotech within [**] business days from the observation of
Deviations ([**] with respect to Significant Deviations).  All deviations will
be investigated and fully documented by Agilent. This documentation will be
retained

 

46

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

 

as part of the batch documentation for the batch affected. When deemed
necessary, Ophthotech reserves the right to request additional or more in-depth
investigation of the Deviation by Agilent.  Ophthotech prior approval shall be
obtained in writing for any planned Significant Deviation. Agilent shall not
release any Batch which includes a Deviation.

 

5.2.2.                  All deviations will be assessed for potential API
quality impact according to Agilent internal procedures and will be fully
documented by Agilent. Investigations will include appropriate justification,
scientific rationale and supporting data.

 

5.2.3.                  Agilent will notify Ophthotech of confirmed OOS results
within [**] business day of notification to Agilent QA that the OOS has
occurred. Agilent will perform the OOS investigation as per Agilent internal
procedures. Agilent shall provide Ophthotech written notice of any changes to
its SOPs or other internal procedures relating to OOS investigations and shall,
upon Ophthotech’s request, make such changed procedures available for Ophthotech
review

 

6.                                      (23) Attachments

 

6.1.                            Contact Information

 

47

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

 

 

6.1.1       ATTACHMENT 1 — CONTACT INFORMATION

 

Ophthotech Mailing Address:

 

Ophthotech Corporation

One Penn Plaza, 35th Floor

New York, New York 10119

 

Ophthotech Contact Information

 

Name

 

Title

 

Phone

 

E-Mail

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

 

Agilent Technologies Mailing Address

 

Agilent Technologies, Incorporated

5555 Airport Blvd.

Boulder, CO  80301

 

Agilent Technologies Contact Information

 

Name

 

Title

 

Phone

 

E-Mail

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

 

48

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

 

6.2.                            Attachment 2

 

6.2.1.                  Manufacturing and Supply Agreements to be added as they
are agreed

 

49

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

 

EXHIBIT D

 

MEMORANDUM OF INSURANCE

 

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

 

 

MEMORANDUM OF INSURANCE

 

MEMORANDUM OF INSURANCE

DATE
10-Apr-2014

 

This Memorandum is issued as a matter of information only to authorized viewers
for their internal use only and confers no rights upon any viewer of this
Memorandum. This Memorandum does not amend, extend or alter the coverage
described below. This Memorandum may only be copied, printed and distributed
within an authorized viewer and may only be used and viewed by an authorized
viewer for its internal use. Any other use, duplication or distribution of this
Memorandum without the consent of [**] is prohibited. “Authorized viewer” shall
mean an entity or person which is authorized by the insured named herein to
access this Memorandum via [**]. The information contained herein is as of the
date referred to above. [**] shall be under no obligation to update such
information.

 

PRODUCER

[**]

COMPANIES AFFORDING COVERAGE

Co A  [**]

 

 

INSURED

Co B

 

Agilent Technologies, Inc.

5301 Stevens Creek Blvd.

Co C

 

M/S 1B-08, Santa Clara

California 95051

United States

Co D

 

 

COVERAGES

 

 

 

THE POLICIES OF INSURANCE LISTED BELOW HAVE BEEN ISSUED TO THE INSURED NAMED
ABOVE FOR THE POLICY PERIOD INDICATED. NOTWITHSTANDING ANY REQUIREMENT, TERM OR
CONDITION OF ANY CONTRACT OR OTHER DOCUMENT WITH RESPECT TO WHICH THIS
MEMORANDUM MAY BE ISSUED OR MAY PERTAIN, THE INSURANCE AFFORDED BY THE POLICIES
DESCRIBED HEREIN IS SUBJECT TO ALL THE TERMS, EXCLUSIONS AND CONDITIONS OF SUCH
POLICIES. LIMITS SHOWN MAY HAVE BEEN REDUCED BY PAID CLAIMS.

 

CO
LTR

 

TYPE OF
INSURANCE

 

POLICY
NUMBER

 

POLICY
EFFECTIVE
DATE

 

POLICY
EXPIRATION
DATE

 

LIMITS
LIMITS IN USD UNLESS OTHERWISE INDICATED

 

 

 

 

 

 

 

 

 

 

 

A

 

GENERAL

 

[**]

 

[**]

 

[**]

 

GENERAL AGGREGATE

 

 

 

LIABILITY

 

 

 

 

 

 

 

PRODUCTS - COMP/OP AGG

[**]

 

 

Commercial

 

 

 

 

 

 

 

PERSONAL AND ADV INJURY

[**]

 

 

General

 

 

 

 

 

 

 

EACH OCCURRENCE

[**]

 

 

Liability

 

 

 

 

 

 

 

FIRE DAMAGE (ANY ONE FIRE)

[**]

 

 

Occurrence

 

 

 

 

 

 

 

MED EXP (ANY ONE PERSON)

[**]

 

 

 

 

 

 

 

 

 

 

 

 

A

 

AUTOMOBILE

 

[**]

 

[**]

 

[**]

 

COMBINED SINGLE LIMIT

[**]

 

 

LIABILITY

 

 

 

 

 

 

 

BODILY INJURY (PER PERSON)

 

 

 

Any Auto

 

 

 

 

 

 

 

BODILY INJURY (PER ACCIDENT)

 

 

 

 

 

 

 

 

 

 

 

PROPERTY DAMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

EXCESS

 

 

 

 

 

 

 

EACH OCCURRENCE

 

 

 

LIABILITY

 

 

 

 

 

 

 

AGGREGATE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GARAGE

 

 

 

 

 

 

 

AUTO ONLY (PER ACCIDENT)

 

 

 

LIABILITY

 

 

 

 

 

 

 

OTHER THAN AUTO ONLY:

 

 

 

 

 

 

 

 

 

 

 

EACH ACCIDENT

 

 

 

 

 

 

 

 

 

 

 

AGGREGATE

 

 

 

 

 

 

 

 

 

 

 

 

 

A

 

WORKERS

 

[**]

 

[**]

 

[**]

 

 

 

 

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

 

 

 

COMPENSATION

 

 

 

 

 

 

 

WORKERS COMP LIMITS

Statutory

 

 

/ EMPLOYERS

 

 

 

 

 

 

 

EL EACH ACCIDENT

[**]

 

 

LIABILITY

 

 

 

 

 

 

 

EL DISEASE - POLICY LIMIT

[**]

 

 

THE PROPRIETOR /

 

 

 

 

 

 

 

EL DISEASE - EACH EMPLOYEE

[**]

 

 

PARTNERS / EXECUTIVE OFFICERS ARE Included

 

 

 

 

 

 

 

 

 

 

The Memorandum of Insurance serves solely to list insurance policies, limits and
dates of coverage. Any modifications here to are not authorized.

 

MEMORANDUM OF INSURANCE

DATE
10-Apr-2014

 

This Memorandum is issued as a matter of information only to authorized viewers
for their internal use only and confers no rights upon any viewer of this
Memorandum. This Memorandum does not amend, extend or alter the coverage
described below. This Memorandum may only be copied, printed and distributed
within an authorized viewer and may only be used and viewed by an authorized
viewer for its internal use. Any other use, duplication or distribution of this
Memorandum without the consent of [**] is prohibited. “Authorized viewer” shall
mean an entity or person which is authorized by the insured named herein to
access this Memorandum via [**] The information contained herein is as of the
date referred to above. [**] shall be under no obligation to update such
information.

 

PRODUCER

[**]

INSURED

Agilent Technologies, Inc.

5301 Stevens Creek Blvd.
M/S 1B-08, Santa Clara

California 95051

United States

 

ADDITIONAL INFORMATION

Work Comp/Employers Liability

 

<br /> All states coverage except [**]

 

<br /> Work Comp excludes: [**]

 

The Memorandum of Insurance Serves solely to list insurance policies, limits and
dates of coverage. Any modifications hereto are not authorized.

 

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

 

 

EXHIBIT E

 

STATEMENTS OF WORK

 

Agilent

 

 

 

 

SOW/Document

 

 

 

 

Number

 

Date

 

Title

Q07-08-56

 

JUL 9, 2008

 

[**]

Q01-10-19B

 

JAN 22, 2010

 

[**]

Q02-10-23B

 

MAR 1, 2010

 

[**]

Q03-10-37

 

APR 7, 2010

 

[**]

Q04-11-58B

 

JUN 24, 2011

 

[**]

Q07-11-82

 

JUL 29, 2011

 

[**]

Q09-11-106

 

OCT 6, 2011

 

[**]

Q04-12-30

 

APR 19, 2012

 

[**]

Q07-12-49

 

JUN 24, 2012

 

[**]

Q08-11-92C

 

SEP 18, 2012

 

[**]

Q03-13-52B

 

MAY 17, 2013

 

[**]

Q03-13-55

 

MAR 21, 2013

 

[**]

Q12-12-24C

 

MAR 21, 2013

 

[**]

Q02-13-39

 

APR 2, 2013

 

[**]

Q11-12-12D

 

APR 29, 2013

 

[**]

Q08-13-99

 

AUG 13, 2013

 

[**]

Q08-13-109

 

AUG 23, 2013

 

[**]

Q08-13-101

 

SEP 11, 2013

 

[**]

Q08-13-116

 

SEP 30, 2013

 

[**]

Q12-13-15B

 

Jan 14, 2014

 

[**]

Q11-13-05B

 

Jan 27, 2014

 

[**]

Q01-14-26

 

Feb 11, 2014

 

[**]

Q02-14-34

 

Feb 12, 2014

 

[**]

Q01-14-23D

 

Feb 18, 2014

 

[**]

 

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

 

EXHIBIT F

 

LIST OF PATENTS

 

Pursuant to Section 9.6.1 of the Agreement, the following Patents that cover the
Process are [**]

 

[**]

 

Country/Treaty

 

Patent/Application #

 

Title

 

Filing Date

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

Country/Treaty

 

Patent/Application #

 

Title

 

Filing Date

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

[**]

 

[**]

 

[**]

 

[**]

 

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

 

EXHIBIT G

 

CONFIDENTIALITY AGREEMENT

 

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

 

[g141821kg17i001.jpg]

 

CONFIDENTIALITY AGREEMENT

 

This Agreement dated 22 March, 2011 (the “Effective Date”), between Ophthotech
Corporation, a Delaware corporation (“Ophthotech”) with offices at 5 Vaughn
Drive, Suite 106, Princeton, New Jersey, 08540, and Agilent Technologies , a
Delaware corporation (“Agilent”) with office at 5555 Airport Blvd # 100,
Boulder, CO 80301-2648

 

1.                                      Background.  Ophthotech and Agilent
(hereinafter collectively referred to as the “Parties”, respectively as the
“Party”) intend to engage in discussions relating to the development,
manufacture, and testing of Ophthotech Drug Substance and Drug Products
including E10030 and ARC1905 and other, as mutually agreed to between the
Parties (the “Purposes”).  In the course of these discussions it is anticipated
that each Party will disclose or deliver to the other Party and to the other
Party’s contractors and designees,(collectively, the “Representatives”) certain
of its trade secrets or confidential or proprietary information for the purposes
of enabling the other Party to perform its obligations under the Purposes.  The
Parties have entered into this Agreement in order to assure the confidentiality
of such trade secrets and confidential or proprietary information in accordance
with the terms of this Agreement.  As used in this Agreement, the Party
disclosing Proprietary Information (as defined below) is referred to as the
“Disclosing Party”; the Party receiving such Proprietary Information is referred
to as the “Recipient”.

 

2.                                      Proprietary Information.  As used in
this Agreement, the term “Proprietary Information” shall mean all trade secrets
or confidential or proprietary information designated as such in writing by the
Disclosing Party, whether by letter or by the use of an appropriate proprietary
stamp or legend, prior to or at the time any such trade secret or confidential
or proprietary information is disclosed by the Disclosing Party or the
Disclosing Party’s Representatives to the Recipient or the Recipient’s
Representatives.  Notwithstanding the foregoing, information which is orally or
visually disclosed to the Recipient by the Disclosing Party, or is disclosed in
writing without an appropriate letter, proprietary stamp or legend, shall
constitute Proprietary Information if (i) it would be apparent to a reasonable
person, familiar with the Disclosing Party’s business and the industry in which
it operates, that such information is of a confidential or proprietary nature
the maintenance of which is important to the Disclosing Party or if (ii) the
Disclosing Party, within [**] days after such disclosure, delivers to the
Recipient a written document or documents describing such Proprietary
Information and referencing the place and date of such oral, visual or written
disclosure and the names of the Representatives of the Recipient to whom such
disclosure was made.  In addition, the term “Proprietary Information” shall be
deemed to include: (a) any notes, analyses, compilations, studies,
interpretations, memoranda or other documents prepared by the Recipient or its
Representatives which contain, reflect or are based upon, in whole or in part,
any Proprietary Information furnished to the Recipient or its Representatives
pursuant hereto; and (b) the existence or status of, and any information
concerning, the discussions between the Parties concerning the possible
establishment of a business relationship.

 

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

 

3.                                      Scope of Agreement.  This Agreement
shall apply to all Proprietary Information disclosed between the Parties hereto
from the Effective Date until third anniversary of the Effective Date.

 

4.                                      Use and Disclosure of Proprietary
Information.  The Recipient and its Representatives shall use Proprietary
Information only for the Purposes and such Proprietary Information shall not be
used for any other purpose without the prior written consent of the Disclosing
Party.  The Recipient and its Representatives shall hold in confidence, and
shall not disclose Proprietary Information; provided, however, that (i) the
Recipient may make any disclosure of such information to which the Disclosing
Party gives its prior written consent; and (ii) any of the Proprietary
Information may be disclosed by the Recipient to its Representatives who need to
know such information in connection with the Purposes and who are informed of
the confidential nature of such information and of the terms of this Agreement. 
In any event, the Recipient shall be responsible for any breach of this
Agreement by any of its Representatives, and agrees, at its sole expense, to
take reasonable measures to restrain its Representatives from prohibited or
unauthorized disclosure or use of the Proprietary Information.  Notwithstanding
anything contained in this Agreement to the contrary, this Agreement shall not
prohibit the Recipient from disclosing Proprietary Information of the Disclosing
Party to the extent required in order for the Recipient to comply with
applicable laws and regulations, provided that the Recipient provides prior
written notice of such required disclosure to the Disclosing Party.

 

5.                                      Limitation on Obligations.  The
obligations of the Recipient specified in Section 4 and 7 shall not apply, and
the Recipient shall have no further obligations, with respect to any Proprietary
Information to the extent that such Proprietary Information:

 

(a)                                 is generally known to the public at the time
of disclosure or becomes generally known without the Recipient or its
Representatives violating this Agreement;

 

(b)                                 is in the Recipient’s possession at the time
of disclosure;

 

becomes known to the Recipient through disclosure by sources other than the
Disclosing Party without such sources violating any confidentiality obligations
to the Disclosing Party; or

 

(c)                                  is independently developed by the Recipient
without reference to or reliance upon Proprietary Information.

 

6.                                      Ownership of Proprietary Information. 
The Recipient agrees that it shall not receive any right, title or interest in,
or any license or right to use, Proprietary Information or any Disclosing
Party’s patent, copyright, trade secret, trademark or other intellectual
property rights therein, by implication or otherwise.  Each of the Parties
hereto represents, warrants and covenants that the trade secrets herein which it
discloses to the other Party pursuant to this Agreement have not been stolen,
appropriated, obtained or converted without authorization.

 

7.                                      Return of Proprietary Information.  The
Recipient shall, upon the written request of the Disclosing Party, return to the
Disclosing Party all Proprietary Information (and all copies and reproductions
thereof).  In addition, the Recipient shall destroy:  (i) the part of any notes,

 

2

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

 

reports or other documents prepared by the Recipient which contain Proprietary
Information; and (ii) any Proprietary Information (and all copies and
reproductions thereof) which is in electronic form or cannot otherwise be
returned to the Disclosing Party.  Alternatively, upon written request of the
Disclosing Party, the Recipient shall destroy all Proprietary Information from
the Disclosing Party (and all copies and reproduction thereof) and the part of
any notes, reports or other documents prepared by the Recipient which contain
Proprietary Information.  Notwithstanding the return or destruction of the
Proprietary Information, the Recipient and its Representatives will continue to
be bound by their obligations specified in Section 4, 5 and 7.

 

8.                                      Miscellaneous.

 

(a)                                 This Agreement supersedes all prior
agreements, written or oral, between the Patties relating to the subject matter
of this Agreement.  This Agreement may not be assigned modified, changed or
discharged, in whole or in part, except by an agreement in writing signed by the
Parties.

 

(b)                                 This Agreement will be binding upon and
inure to the benefit of the Parties and their respective heirs, successors and
assigns.  Notwithstanding the forgoing, such heirs, successors and assignments
shall not release such assigning Party from any of its obligations under this
Agreement.

 

(c)                                  This Agreement shall be construed and
interpreted in accordance with the internal laws of the State of New Jersey,
without giving effect to the principles of conflicts of law thereof.

 

(d)                                 The provisions of this Agreement are
necessary for the protection of the business and goodwill of the Patties and are
considered by the Parties to be reasonable for such purpose.  The Recipient
agrees that any breach of this Agreement will cause the Disclosing Party
substantial and irreparable injury and, therefore, in the event of any such
breach, in addition to other remedies which may be available, the Disclosing
Party shall have the right to specific performance and other injunctive and
equitable relief.

 

(e)                                  The obligations of the Recipient specified
in Section 4, 5 and 7 imposed by this Agreement shall continue until the [**]
anniversary of the Effective Date.

 

(f)                                   For the convenience of the Parties, this
Agreement may be executed by facsimile and in counterparts, each of which shall
be deemed to be an original, and both of which taken together, shall constitute
one agreement binding on both Parties.

 

3

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

 

EXECUTED as of the day and year first set forth above.

 

AGILENT TECHNOLOGIES

 

OPHTHOTECH CORPORATION

 

 

 

 

 

 

By:

/s/ James Powell

 

By:

/s/ Richard Everett

 

 

 

Name: James Powell

 

Name: Richard Everett

 

 

 

Title: General Manager NASD

 

Title: VP, CMC Operations

 

4

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

 

 

AMENDMENT #1
TO
CONFIDENTIALITY AGREEMENT
BY AND BETWEEN
AGILENT TECHNOLOGIES, INC.
AND
OPHTHOTECH CORPORATION

 

This Amendment # 1 (“Amendment”) amends the Confidentiality Agreement by and
between Agilent Technologies, Inc. (“Agilent”) and Ophthotech Corporation
(“Ophthotech”) dated as of 22 March 2011 (the “Agreement”).

 

Agilent and Ophthotech hereby agree to amend the Agreement as follows:

 

1.                                      Section 3, Scope of Agreement, is hereby
deleted in its entirety and replaced with the following:

 

“This Agreement shall apply to all Proprietary Information disclosed between the
Parties hereto from the Effective Date until the tenth anniversary of the
Effective Date.”

 

2.                                      Section 8(e) is hereby deleted in its
entirety and replaced with the following:

 

“The obligations of the Recipient specified in Section 4, 5 and 7 imposed by
this Agreement shall continue until the [**] anniversary of the expiration or
termination of this Agreement.”

 

3.                                      This Amendment shall take effect as of
22 March 2014.

 

4.                                      This Amendment constitutes the entire
agreement between the parties and incorporates all prior agreements and
amendments by reference.  Except as; expressly amended by this Amendment, all
other terms and conditions of the Agreement shall remain in full force and
effect.  All capitalized terms used in this Amendment but not otherwise defined
herein, shall have the meaning assigned to them in the Agreement.

 

AGREED:

 

 

 

AGILENT TECHNOLOGIES, INC.

OPHTHOTECH CORPORATION

 

 

By:

/s/ Nelson Thune

 

By:

/s/ Barbara A. Wood

 

 

 

 

 

Name:

Nelson Thune

 

Name:

Barbara A. Wood

 

 

 

 

 

Title:

General Manager

 

Title:

SVP, General Counsel and Corporate Secretary

 

 

 

 

 

Date:

02 May 2014

 

Date:

14 April 2014

 

5

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

 

EXHIBIT H

 

[**] PROCESS FLOW

 

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission.

 

A total of two pages were omitted. [**].

 

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

 

EXHIBIT I

 

COMMERCIAL SUPPLY AGREEMENT TERMS

 

Terms used but not defined below shall have the meaning set forth in the
Agreement.

 

Exclusivity.  During the term of the Commercial Supply Agreement and for a
period of five (5) years thereafter (subject to the termination provisions as
mutually agreed to by the Parties), Agilent will only supply Anti-PDGF Aptamer
APIs to Customer and any Affiliate of Customer or Third Party designated by
Customer.

 

Primary Supplier.  During the term of the Commercial Supply Agreement, Customer
will purchase from Agilent at least [**] percent ([**]%) of its requirements of
Product for use in the United States, European Union, and any additional future
jurisdictions as mutually agreed to by the Parties in writing (“Territory”).

 

Capacity.  In the event that the Product gains regulatory approval, Agilent will
provide capacity to manufacture accepted purchase orders for up to [**] Kilos of
Product per calendar year for Ophthotech’s needs.  Should [**] Kilos of Product
no longer be sufficient, the Parties will negotiate in good faith increased
capacity to be dedicated to Ophthotech.

 

Pricing.  Pricing for the Product will be negotiated in good faith by the
Parties.  Pricing for the Product shall be structured on a tiered basis with the
price reduced as the volume ordered increases and the process is scaled up to
produce larger volumes per batch.  Pricing for the Product shall not exceed the
pricing for Product as set forth in Exhibit J except to the extent that the
Manufacturing Standards as of the Effective Date are materially modified
pursuant to the Change Management provisions set forth in the Quality
Agreement.  In the event of any such change in the Manufacturing Standards, any
increase in pricing shall be proportionate to the increase in Agilent’s costs to
manufacture Product based on such modified Manufacturing Standards.

 

Supply Failures.  The Commercial Supply Agreement will include provisions
detailing the rights and obligations in the event that Agilent fails to supply
specified percentages of Product ordered by Customer under the Commercial Supply
Agreement during a defined period of time, which rights will include a release
from Customer’s obligation to purchase [**]% of its requirements of Product for
use in the Territory.

 

Term.  The Commercial Supply Agreement will have an initial term that ends five
(5) years from the date of Customer’s first commercial sale of the approved
Finished Product.  After the initial term, the Commercial Supply Agreement will
renew for an indefinite period.  Either Party may terminate the Commercial
Supply Agreement at the end of the initial term or during the renewal term
provided, however, that it has given the other Party at least eighteen (18)
months prior written notice of termination.

 

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

 

EXHIBIT J

 

PRODUCT PRICING

 

Pursuant to Section 6.1 of the Agreement, the following table provides not to
exceed Product pricing based on quantities ordered via a single Purchase Order.

 

Quantity Ordered

 

Not to Exceed Price

 

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

[**]

 

 

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