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CONFIDENTIAL
EXECUTION VERSION

AMENDED AND RESTATED DEVELOPMENT AND COMMERCIALIZATION LICENSE AGREEMENT
This Amended and Restated Development and Commercialization License Agreement
(the “Agreement”) is entered into as of May 12, 2020 (the “Amendment Execution
Date”) and is made effective as of January 1, 2020 (the “Amendment Effective
Date”), by and between Pfizer Inc., a Delaware corporation with offices located
at 235 East 42nd Street, New York, New York 10017 (“Pfizer”) and OPKO Ireland
Ltd., an entity organized and existing under the laws of Ireland (“OPKO”).
Pfizer and OPKO are referred to herein individually as a “Party” and
collectively as the “Parties.”
RECITALS
WHEREAS, OPKO and Pfizer are parties to that certain Development and
Commercialization Agreement, dated December 13, 2014 (the “Original Execution
Date”), as amended by those certain letter agreements between OPKO and Pfizer
dated as of December 13, 2018 and December 19, 2018 (as amended, the “Original
Agreement”), whereby, inter alia, OPKO granted an exclusive license of Licensed
Technology owned or otherwise Controlled by OPKO in the Territory to Pfizer
(each as defined therein); and
WHEREAS, OPKO and Pfizer now wish to amend and restate the Original Agreement in
its entirety to make such changes as set forth herein, with the effect that the
Original Agreement shall be superseded and replaced in its entirety by this
Agreement.
NOW, THEREFORE, in consideration of the mutual covenants and agreements provided
herein, the Parties hereby agree that the Original Agreement is superseded and
replaced in its entirety by this Agreement as of the Amendment Effective Date as
follows:
1. DEFINITIONS.
1.1. “AAA” has the meaning set forth in Schedule 11.14.
1.2. “Accounting Standards” means GAAP and International Financial Reporting
Standards or other applicable international accounting standard in use, in each
case as applicable and consistently applied by the relevant Person.
1.3. “Additional Pediatric Indication” has the meaning set forth in
Section 3.10.3(b)(i).

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1.4. “Affiliate” means, as of any point in time and for so long as such
relationship continues to exist with respect to any Person, any Person that
controls, is controlled by or is under
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common control with such Person. A Person shall be regarded as in control of
another Person if it (a) owns or controls at least fifty percent (50%) of the
equity securities of the subject Person entitled to vote in the election of
directors or (b) possesses, directly or indirectly, the power to direct or cause
the direction of the management or policies of any such Person (whether through
ownership of securities or other ownership interests, by contract or otherwise);
provided, however, that where an entity owns a majority of the voting power
necessary to elect a majority of the board of directors or other governing board
of another entity, but is restricted from electing such majority by contract or
otherwise, such entity will not be considered to be in control of such other
entity until such time as such restrictions are no longer in effect.
1.5. “AGHD,” or “Adult Growth Hormone Deficiency” means growth hormone
deficiency in adult patients, whether as a result of adult onset or childhood
onset causes.
1.6. “Agreement” has the meaning set forth in the Preamble.
1.7. “Amendment Effective Date” has the meaning set forth in the Preamble.
1.8. “Amendment Execution Date” has the meaning set forth in the Preamble.
1.9. “Applicable Law” means any law (including common law), statute, rule,
regulation, order, judgment, or ordinance of any Governmental Authority,
including those concerning environmental, health, and safety matters.
1.10. “Approved CRO” has the meaning set forth in Section 3.1.11(a).
1.11. “Approved Indication” means, with respect to a Licensed Product, a
specific human disease or condition for which the treatment or prevention has
received Regulatory Approval.
1.12. “Approved Vendor” has the meaning set forth in Section 3.1.11(b).
1.13. “Audited Party” has the meaning set forth in Section 5.8.2.
1.14. “Auditing Party” has the meaning set forth in Section 5.8.2.
1.15. “Auditing Plan” has the meaning set forth in Section 4.7.1.
1.16. “Bankruptcy Code” has the meaning set forth in Section 9.4.1.
1.17. “Bankruptcy Event” has the meaning set forth in Section 9.4.1.
1.18. “Binding Obligation” means, with respect to a Party, (a) any oral or
written agreement or arrangement that binds or affects such Party’s operations
or property, including any assignment, license agreement, loan agreement,
guaranty, or financing agreement, (b) the provisions of such Party’s charter,
bylaws, or other organizational documents, or (c) any order, writ, injunction,
decree, or judgment of any court or Governmental Authority entered against such
Party or by which any of such Party’s operations or property are bound.
1.19. “Biosimilar Product” means a pharmaceutical product which, with respect to
a Licensed Product (a) has been licensed as a biosimilar or interchangeable
product by the FDA pursuant to Section 351(k) of the Public Health Service Act
(42 U.S.C. § 262(k)), as may be amended, or any subsequent or superseding law,
statute or regulation, (b) has been authorized as a similar biological medicinal
product in the EU pursuant to Directive 2001/EC/83, as may be amended, or any
subsequent or superseding law, statute or regulation, or (c) has otherwise
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achieved analogous regulatory approval based upon reference to a Licensed
Product from another applicable Regulatory Authority.
1.20. “BLA” means a Biologics License Application for Regulatory Approval filed
with the FDA in the United States pursuant to Section 351(a) of the Public
Health Service Act (42 U.S.C. 262(a) or any successor statutes or regulations),
or any foreign equivalent thereof.
1.21. “Brief” has the meaning set forth in Schedule 11.14.
1.22. “Business Day” means a day other than a Saturday, Sunday or bank or other
public holiday in New York, New York.
1.23. “Calendar Quarter” means the respective periods of three consecutive
calendar months ending on March 31, June 30, September 30 and December 31.
1.24. “CDA” has the meaning set forth in Section 11.18.
1.25. “Chairperson” has the meaning set forth in Section 3.2.2.
1.26. “Clinical Data Package” has the meaning set forth in Section 3.4.2.
1.27. “Clinical Dataset” has the meaning set forth in Section 3.4.3(a).
1.28. “Clinical Investigator” means the principal investigator at each Site.
1.29. “Clinical Investigator Meeting” has the meaning set forth in Section
4.2.2(a).
1.30. “Clinical Trial Agreement” has the meaning set forth in Section 4.2.1(b).
1.31. “Clinical Trial Registries” has the meaning set forth in Section 3.3.4(a).
1.32. “CMC Information” means the chemistry, manufacturing and control
information required for the submission of a BLA.
1.33. “Commercialize” means all activities required or directed to market,
promote, distribute, offer for sale, sell, have sold, import, have imported,
export, have exported or otherwise commercialize a pharmaceutical product or
device, including activities ***. When used as a noun, “Commercialization” means
any and all activities involved in Commercializing.
1.34. “Commercially Reasonable Efforts” means, with respect to the efforts to be
expended by a Party with respect to any objective, subject to Section 11.6,
those reasonable, good faith efforts and resources to accomplish such objective
as such Party and its Affiliates would normally use to accomplish a similar
objective under similar circumstances, in each case taking into account all
Relevant Factors in effect at the time such efforts are to be expended. With
respect to any efforts relating to the Development, Regulatory Approval and/or
Commercialization of a Compound or Licensed Product, generally or with respect
to any particular country in the Territory, such Party will be deemed to have
exercised Commercially Reasonable Efforts if such Party has exercised those
efforts normally used by such Party and its Affiliates, in the relevant country,
with respect to a compound, product or product candidate Controlled by such
Party and/or its Affiliates which is of ***, in each case taking into account
all Relevant Factors in effect at the time such efforts are to be expended***.
1.35. “Compliance” means the adherence by the Parties in all material respects
to all Applicable Laws, in each case with respect to the activities to be
conducted under this Agreement.
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1.36. “Compound” means any human growth hormone (hGH) polypeptide ***.
1.37. “Confidential Information” has the meaning set forth in Section 7.1.
1.38. “Control” means, with respect to any Intellectual Property Right or
material (including any Patent Right, Know-How or other data, information or
material), the ability (whether by sole, joint or other ownership interest,
license or otherwise) to, without violating the terms of any agreement with a
Third Party, grant the relevant license or sublicense or provide or provide
access or other right in, to or under such Intellectual Property Right or
material.
1.39. “Cost of Goods Sold” or “COGS” means, for Genotropin Products or Licensed
Products, as the case may be, as reasonably determined on a *** basis, (a) with
respect to product Manufactured by the Party reporting Net Sales, the
Manufacturing Cost of such product; (b) with respect to product purchased by the
Party reporting Net Sales from the other Party, the Manufacturing Cost of such
product; (c) with respect to product purchased by the Party reporting Net Sales
from a Third Party, such Party’s cost of acquisition of such product; and (d)
with respect to product Manufactured by the Party reporting Net Sales and sold
to a Third Party, the Manufacturing Cost of such product, together in the case
of (a), (b), (c) and (d) with other costs incurred by such Party and allocable
to such product in accordance with Accounting Standards, including the costs of
quality assurance and storage. For clarity, Pfizer agrees to allocate all
aforementioned costs on a *** basis consistent with its internal accounting
policy, such that *** are only applied as a reduction of Net Sales in that same
*** (i.e., *** apply only to Net Sales in the *** and are not applied to reduce
the Net Sales in the *** or ***).
1.40. “CRO” means a contract research organization.
1.41. “CRO Agreement” has the meaning set forth in Section 3.1.11(a).
1.42. “CTA” means a Clinical Trial Application submitted to a Regulatory
Authority, the submission and approval of which is necessary to initiate or
conduct clinical testing of a pharmaceutical product in humans in such
jurisdiction.
1.43. “CTP Technology” means any Intellectual Property Rights, compositions,
compounds or products including or relating to or directed towards the fusion
with or conjugation of a polypeptide to at least one C-terminal peptide (CTP),
or fragment thereof sufficient to increase the half-life of the polypeptide.
1.44. “Data Management Plan” has the meaning set forth in Section 4.5.2(a).
1.45. “Develop” or “Developing” means to discover, research or otherwise develop
a process, compound, device or product, including conducting non-clinical and
clinical research and development activities. When used as a noun, “Development”
means any and all activities involved in Developing.
1.46. “Development Budget” has the meaning set forth in Section 3.1.5.
1.47. “***” has the meaning set forth in Section 3.1.13.
1.48. “Development Plan” has the meaning set forth in Section 3.1.1(a).
1.49. “Device” means a proprietary delivery system for subcutaneous delivery of
any Compound.
1.50. “DG44 Materials” has the meaning set forth in Section 8.4.7.
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1.51. “Diligence Issue” has the meaning set forth in Section 3.10.2.
1.52. “Disclosed Third Party Agreement” has the meaning set forth in Section
8.3.11.
1.53. “Disclosing Party” has the meaning set forth in Section 7.2.
1.54. “EMA” means the European Medicines Agency and any successor agency or
authority thereto.
1.55. “EU Regulatory Approval” means the first approval of an MAA for a Licensed
Product in the EU.
1.56. “***” means the *** as of the Original Execution Date and to the extent
*** following the Original Effective Date, ***.
1.57. “***” means that period beginning on the *** on termination of this
Agreement in its entirety or termination of this Agreement for the *** as
permitted pursuant to ***.
1.58. “European Union” or “EU” or “E.U.” means the member states of the European
Union, as may exist from time to time, which as of the Original Execution Date
include Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark,
Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia,
Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania,
Slovakia, Slovenia, Spain, Sweden and the United Kingdom and all other countries
that accede to the European Union during the term of this Agreement. For
clarity, ***.
1.59. “Existing Trials” has the meaning set forth in Section 3.12.
1.60. “FDA” means the United States Food and Drug Administration and any
successor agency or authority thereto.
1.61. “Field” means all human therapeutic uses of human growth hormone (hGH) for
long-lasting (not daily) administration.
1.62. “Financial Disclosure Form” has the meaning set forth in Section 4.2.1(c).
1.63. “First Commercial Sale” means, on a Licensed Product-by-Licensed Product
and country-by-country basis, the first sale by Pfizer or an Affiliate or
permitted sublicensee of Pfizer to a Third Party in such country or for end use
or consumption of such Licensed Product in a country, after such Licensed
Product has been granted Regulatory Approval (for clarity, including Price
Approval) by the appropriate Regulatory Authority(ies) for such country. A First
Commercial Sale excludes any sale or other distribution for use in a clinical
trial or other Development activity, promotional use (including samples), or for
compassionate use or on a named patient basis.
1.64. “Force Majeure” has the meaning set forth in Section 11.7.
1.65. “Franchise Gross Profit” means *** applied on a *** basis in the Territory
in the applicable calendar year (prorated for any partial calendar year).
1.66. “Franchise Net Sales” means *** in the Territory in the applicable
calendar year (prorated for any partial calendar year).
1.67. “GAAP” means United States generally accepted accounting principles,
consistently applied.
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1.68. “Genotropin” has the meaning set forth in Section 1.70.
1.69. “Genotropin Divestment” means the event upon which *** in which case, any
and all ***. For the purposes of this definition, divestment shall include any
transaction that ***.
1.70. “Genotropin Products” means the pharmaceutical products listed on
Schedule 1.70 (“Genotropin”) *** in the first *** following the First Commercial
Sale of Licensed Product for PGHD.
1.71. “Good Clinical Practices” or “GCP” means all applicable good clinical
practice standards for the design, conduct, performance, monitoring, auditing,
recording, analyses and reporting of clinical trials, including, as applicable,
(a) the International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (“ICH”) Harmonised Tripartite
Guideline for Good Clinical Practice (CPMP/ICH/135/95) and any other guidelines
for good clinical practice for clinical trials on medicinal products in the EU;
(b) the Declaration of Helsinki (2004), as last amended at the 52nd World
Medical Association General Assembly in October 2000, and any further amendments
or clarifications thereto; and (c) the equivalent Applicable Laws in any
relevant country, each as may be amended and applicable from time to time and,
in each case, that provide for, among other things, assurance that the clinical
data and reported results are credible and accurate and protect the rights,
integrity, and confidentiality of trial subjects.
1.72. “Government Official” means (a) any elected or appointed government
official (e.g., a member of a ministry of health), (b) any employee or Person
acting for or on behalf of a government official, Governmental Authority, or
other enterprise performing a governmental function, (c) any political party,
candidate for public office, officer, employee, or Person acting for or on
behalf of a political party or candidate for public office, and (d) any employee
or Person acting for or on behalf of a public international organization (e.g.,
the United Nations). For clarity, healthcare providers employed by
government-owned hospitals will also be considered Government Officials.
1.73. “Governmental Authority” means any court, agency, department, authority or
other instrumentality of any national, state, county, city or other political
subdivision.
1.74.  “HSR Act” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976,
as amended, and the rules and regulations promulgated thereunder.
1.75. “HSR Filing” means filings by OPKO and Pfizer with the United States
Federal Trade Commission and the Antitrust Division of the United States
Department of Justice of a Notification and Report Form for Certain Mergers and
Acquisitions (as that term is defined in the HSR Act) with respect to the
matters set forth in this Agreement, together with all required documentary
attachments thereto.
1.76. “IDMC” has the meaning set forth in Section 4.10.
1.77. “IDMC Charter” has the meaning set forth in Section 4.10.
1.78. “IND” means an Investigational New Drug Application submitted under the
United States Federal Food, Drug, and Cosmetic Act, as amended, and the rules
and regulations promulgated thereunder, or an analogous application or
submission with any analogous agency or Regulatory Authority outside of the
United States for the purposes of obtaining permission to conduct clinical
trials.
1.79. “Indemnified Party” has the meaning set forth in Section 10.4.1.
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1.80. “Indemnifying Party” has the meaning set forth in Section 10.4.1.
1.81. “Informed Consent” has the meaning set forth in Section 4.3.2.
1.82. “Infringement Claim” has the meaning set forth in Section 6.6.1.
1.83. “Intellectual Property Rights” means all copyrights, trade secrets,
trademarks, moral rights, Patent Rights, Know-How and any and all other
intellectual property or proprietary rights now known or hereafter recognized in
any jurisdiction.
1.84. “Invoicing Party” has the meaning set forth in Section 3.1.6(a).
1.85. “IRB” means institutional review board.
1.86. “***” means the ***.
1.87. “***” means that period beginning on the ***, and ending on termination of
this Agreement in its entirety or termination of this Agreement for the ***.
1.88. “Japan Regulatory Approval” means the first approval by a PMDA for a
Licensed Product in Japan.
1.89. “JDC” has the meaning set forth in Section 3.2.1.
1.90. “Joint Developed IP” has the meaning set forth in Section 6.1.2(c).
1.91. “Know-How” means any invention, discovery, development, data, information,
process, procedure (including training procedures), method, technique, material
(including any chemical, biological material or other compositions of matter),
technology, result, cell line, compounds, probe, sequence, device or other
know-how, but not any Patent Rights.
1.92. “Liability” has the meaning set forth in Section 10.2.
1.93. “LIBOR” means the rate of interest per annum determined on the basis of
the rate for deposits in U.S. Dollars for a period of thirty (30) days as
published by the Wall Street Journal. If the thirty (30) day LIBOR has been
permanently discontinued, then it will be replaced by a comparable or successor
quoting service mutually agreed to by the Parties and the definition of “LIBOR”
as used herein shall be deemed to be referring to such quoting service.
1.94. “Licensed Activities” has the meaning set forth in Section 6.5.1.
1.95. “Licensed hGH-Specific Patents” means those certain Licensed Patent
Rights, the claim(s) of which claim, recite, pertain to or are directed to a
human growth hormone (hGH) polypeptide ***.
1.96. “Licensed Know-How” means any Know-How that (a) is Controlled by OPKO or
any of its Affiliates as of the Original Effective Date or comes into the
Control of or is developed by OPKO or any of its Affiliates during the Term
(other than through the grant of a license by Pfizer) to the Compound or
Licensed Products; and (b) is directed to any Compound or Licensed Product or to
the Development, Manufacture, Commercialization or use of any of the foregoing.
1.97. “Licensed OPKO Core Patents” means those certain Licensed Patent Rights
including (a) at least one claim that claims, recites, encompasses or is
directed to a human growth hormone (hGH) polypeptide ***. Without limiting the
foregoing, Licensed OPKO Core
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Patents include the Patent Rights set forth on Schedule 1.98(b) as it may be
updated by OPKO from time to time.
1.98. “Licensed Patent Rights” means any Patent Right that (a) is owned by OPKO
as of the Original Effective Date (including the Patent Rights listed in
Schedule 1.98) or comes into the Control of OPKO during the Term (other than
through the grant of a license by Pfizer) and (b) (i) claims or recites any
Compound or Licensed Product (including the composition of matter thereof) or
Licensed Know-How, (ii) claims a method of making any Compound or Licensed
Product, or (iii) claims a method of using any Compound or Licensed Product. For
the avoidance of doubt, Licensed Patent Rights shall include ***.
1.99. “Licensed Product” means any pharmaceutical product containing one or more
Compounds. The Licensed Product may be used with or accompanied by a Device.
1.100. “Licensed Product CMC Activities” means those activities set forth in the
Development Plan under “CMC Development” and relating to the Licensed Product.
1.101. “Licensed Technology” means Licensed Patent Rights and Licensed Know-How.
1.102. “Litigation Conditions” has the meaning set forth in Section 10.4.2.
1.103. “MAA” means Marketing Authorization Application.
1.104. “Major EU Country” means any of France, Germany, Italy, Spain or the
United Kingdom.
1.105. “Major Market Country” means any of ***.
1.106. “Manufacture” or “Manufacturing” means to make, produce, manufacture,
process, fill, finish, package, label, perform quality assurance testing on,
release, ship or store a compound, device or product or any component thereof.
When used as a noun, “Manufacture” or “Manufacturing” means any and all
activities involved in Manufacturing a compound or product or any component
thereof.
1.107. “Manufacturing Activities” has the meaning set forth in
Section 3.1.2(f)(i).
1.108.  “Manufacturing Cost” means***
***
***
1.109. “MEDDEV Guidelines” means those guidelines published by the European
Commission promoting a common approach by manufacturers and notified bodies
involved in the conformity assessment procedures according to the relevant
annexes of the Medical Device Directive and other applicable EU directives, and
by the competent authorities charged with safeguarding public health.
1.110. “Medical Device Directive” means the directive 93/42/EEC, as amended from
time to time.
1.111. “Monitoring Plan” has the meaning set forth in Section 4.8.
1.112. “Net Sales” means, with respect to a Genotropin Product or a Licensed
Product, gross amounts invoiced for sales by Pfizer and its Affiliates and
sublicensees of such Genotropin Product or Licensed Product to Third Parties in
the Territory, less in each case (i) bad debts and uncollectable invoiced
amounts relating to sales of Licensed Product that are actually written off
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in accordance with GAAP, consistently applied throughout Pfizer and its
Affiliates, provided that any such amounts shall be capped at up to *** of Net
Sales per Pfizer Year and any subsequently collected amounts will be included in
the current Net Sales or Gross Profit calculation, as the case may be, (ii)
sales returns and allowances actually paid, granted or accrued, including trade,
quantity and cash discounts and other adjustments, including those granted on
account of price adjustments, returns, rebates, chargebacks or similar payments
granted or given to wholesalers or other institutions, (iii) adjustments arising
from consumer discount programs or other similar programs, (iv) customs or
excise duties, valued-added taxes, sales taxes, consumption taxes and other
taxes (except income taxes) or duties relating to sales, any payment in respect
of sales to the United States government, any state government or any foreign
government, or to any other governmental authority, or with respect to any
government-subsidized program or managed care organization, each to the extent
not already reflected in the amount invoiced, and (v) freight and insurance for
the Licensed Product to the extent included in the amount invoiced. Net Sales
shall be calculated by Pfizer using a method of value allocation consistent with
the method used with Pfizer’s other collaborations. Net Sales shall be
determined from books and records maintained in accordance with the Accounting
Standards, as consistently applied by Pfizer with respect to sales of the
Genotropin Product or Licensed Product.
1.113. “***” means the *** described in ***.
1.114. “***” means those activities set forth in the Development Plan under “CMC
Development” and relating to the ***.
1.115. “New Trials” has the meaning set forth in Section 3.13.
1.116. “Notice of Dispute” has the meaning set forth in Section 11.13.1.
1.117. “OLE Studies” means all ongoing and completed open label extension
studies for the Licensed Product set forth in the Development Plan (as it may be
amended from time to time, including amendments for additional open label
extension studies), ***.
1.118. “OPKO” has the meaning set forth in the Preamble.
1.119. “OPKO Developed IP” has the meaning set forth in Section 6.1.2(b).
1.120. “OPKO Indemnified Party” has the meaning set forth in Section 10.2.
1.121. “OPKO Prosecuted IP” has the meaning set forth in Section 6.3.1(a).
1.122. “OPKO Review Period” has the meaning set forth in Section 7.8.1.
1.123. “OPKO Third Party Agreement” means any agreement between OPKO (or any of
its Affiliates) and any Third Party that could give rise to a Third Party’s
claim on or otherwise relates to OPKO’s ownership of OPKO’s right, title or
interest in or to any Licensed Technology necessary for the Development,
Manufacturing or Commercialization of Licensed Products.
1.124. “Original Agreement” has the meaning set forth in the Recitals.
1.125. “Original Effective Date” means January 28, 2015.
1.126. “Original Execution Date” has the meaning set forth in the Recitals.
1.127. “Partial Termination” has the meaning set forth in Section 9.5.1.
1.128. “Party” and “Parties” have the meaning set forth in the Preamble.
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1.129. “Patent Rights” means any and all (a) issued patents, (b) pending patent
applications, including all provisional applications, substitutions,
continuations, continuations-in-part, divisions and renewals, and all patents
granted thereon, (c) patents-of-addition, reissues, reexaminations and
extensions or restorations by existing or future extension or restoration
mechanisms, including patent term adjustments, patent term extensions,
supplementary protection certificates or the equivalent thereof, (d) inventor’s
certificates, (e) other forms of government-issued rights substantially similar
to any of the foregoing and (f) United States and foreign counterparts of any of
the foregoing.
1.130. “Payments” means all of the payments made by Pfizer and/or its Affiliates
to OPKO and/or its Affiliates pursuant to Article 5 of this Agreement, including
without limitation the upfront payment, regulatory milestone payments, royalty
payments, profit share payments and any adjustments.
1.131. “Pediatric O&E Study” means that certain Trial entitled “A Phase 3,
Randomized, Multicenter, Open-Label, Crossover Study Assessing Subject
Perception of Treatment Burden with Use of Weekly Growth Hormone (Somatrogon)
Versus Daily Growth Hormone (Genotropin®) Injections in Children with Growth
Hormone Deficiency,” as the same may be amended from time to time in accordance
with requests, requirements or other instructions received from any applicable
Regulatory Authority.
1.132. “Pending Phase III PGHD Study” means that certain Trial entitled “Phase
3, open-label, randomized, multicenter, 12 months, efficacy and safety study of
weekly MOD-4023 compared to daily Genotropin® - therapy in pre-pubertal children
with growth hormone deficiency,” as the same may be amended from time to time in
accordance with requests, requirements or other instructions received from any
applicable Regulatory Authority.
1.133. “Person” means an individual, sole proprietorship, partnership, limited
partnership, limited liability partnership, corporation, limited liability
company, business trust, joint stock company, trust, incorporated association,
joint venture or similar entity or organization, including a government or
political subdivision or department or agency of a government.
1.134. “Pfizer” has the meaning set forth in the Preamble.
1.135. “Pfizer Developed CTP IP” has the meaning set forth in Section 2.4.
1.136. “Pfizer Developed IP” has the meaning set forth in Section 6.1.2(a).
1.137. “Pfizer Indemnified Party” has the meaning set forth in Section 10.3.
1.138. “Pfizer Prosecuted IP” has the meaning set forth in Section 6.3.2(a).
1.139. “Pfizer Quarter” means each of the four (4) thirteen (13) week periods
(a) with respect to the United States, commencing on January 1 of any Pfizer
Year and (b) with respect to any country in the Territory other than the United
States, commencing on December 1 of any Pfizer Year.
1.140. “Pfizer Review Period” has the meaning set forth in Section 7.8.2.
1.141. “Pfizer Year” means the twelve (12) month fiscal periods observed by
Pfizer (a) commencing on January 1 with respect to the United States and (b)
commencing on December 1 with respect to any country in the Territory other than
the United States.
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1.142. “PGHD,” or “Pediatric Growth Hormone Deficiency” means growth failure in
pediatric patients due to an inadequate secretion of endogenous growth hormone.
1.143. “Pharmacovigilance Agreement” has the meaning set forth in Section
3.14.1.
1.144. “Phase III Clinical Trial” means a human clinical trial of a compound or
product for an indication on a sufficient number of subjects that is designed to
establish that the compound or product is safe and efficacious for its intended
use, and to determine warnings, precautions, and adverse reactions that are
associated with the compound or product in the dosage range to be prescribed,
and to support Regulatory Approval of the compound or product for such
indication or label expansion of the compound or product. For clarity, the term
“Phase III Clinical Trials” includes early access and compassionate use
programs.
1.145. “Phase IV Clinical Trial” means a human clinical trial conducted after
Regulatory Approval of a product, designed either (a) to extend or expand the
label of indications for which that product is approved or (b) to obtain
additional information regarding the risks, benefits and optimal use of that
product.
1.146. “PMDA” means the Pharmaceuticals and Medical Devices Agency, Japan and
any successor agency or authority thereto.
1.147. “Post-Amendment Effective Date Period” has the meaning set forth in
Section 3.1.2(b).
1.148. “Price Approval” means, in any country or jurisdiction where a
Governmental Authority authorizes reimbursement for, or approves or determines
pricing for, pharmaceutical products, receipt (or, if required to make such
authorization, approval or determination effective, publication) of *** pricing
approval ***.
1.149. “Profit Share Term” means one or more of the *** as the context may
require.
1.150. “PSGA,” or “Pediatric Short for Gestational Age” means growth failure in
children born small for gestational age who fail to manifest catch-up growth by
age two (2) years.
1.151. “Quality Agreement” has the meaning set forth in Section 3.6.2.
1.152. “Receiving Party” has the meaning set forth in Section 7.2.
1.153. “***” or “***” means ***.
1.154. “Regulatory Approval” means, as relevant, each or all regulatory,
technical, medical and scientific licenses, registrations, authorizations and
approvals (including approvals of BLAs, supplements and amendments, pre- and
post- approvals and Price Approvals) necessary for offering for sale, marketing
and sale of a pharmaceutical product and/or device in a regulatory jurisdiction.
1.155. “Regulatory Authority” means, with respect to a particular country, ***,
or jurisdiction, the Governmental Authority having responsibility for granting a
specific Regulatory Approval in such country, ***, or jurisdiction. For clarity,
Regulatory Authority shall, as applicable, include any notified body with
respect to any Device.
1.156. “Regulatory Exclusivity” means any exclusive marketing rights or data
exclusivity rights conferred by any Regulatory Authority with respect to a
Licensed Product in a country, Region, or jurisdiction in the Territory, other
than a Patent Right, including orphan drug
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exclusivity, pediatric exclusivity, rights conferred in the European Union under
Directive 2001/EC/83, or rights similar thereto in other countries or
jurisdictions in the Territory.
1.157. “Regulatory Materials” means, with respect to a Licensed Product for any
particular indication in any particular jurisdiction, regulatory applications
and submissions (and any supplements or amendments thereto), and any
notifications, communications, correspondence, registrations, drug master files,
Regulatory Approvals and/or other filings made to, received from or otherwise
conducted with a Regulatory Authority, including BLAs and INDs, as applicable,
that relate to such Licensed Product in such jurisdiction. Regulatory Materials
also include presentations, responses, and applications for Regulatory
Approvals.
1.158. “Regulatory Milestone” has the meaning set forth in Section 5.2.
1.159. “Regulatory Milestone Payment” has the meaning set forth in Section 5.2.
1.160. “Relevant Factors” means all relevant factors that may affect the
Development, Regulatory Approval or Commercialization of a Compound or Licensed
Product, including (as applicable): actual and potential issues of safety,
efficacy or stability; product profile ***.
1.161. “***” means ***.
1.162. “Representatives” means, with respect to a Party, such Party, its
Affiliates, its sublicensees and each of their respective officers, directors,
employees, consultants, contractors and agents.
1.163. “***” has the meaning set forth in Section 3.1.7(a).
1.164. “Residual Knowledge” means knowledge, techniques, experience and Know-How
that (a) are, or are based on, any Confidential Information Controlled by the
Disclosing Party and (b) are incidentally and unintentionally retained in the
unaided memory of any authorized Representative of the Receiving Party after
having access to such Confidential Information. An individual’s memory will be
considered to be incidentally and unintentionally unaided if the individual has
not intentionally memorized the Confidential Information for the purpose of
retaining and subsequently using or disclosing it. In no event, however, will
Residual Knowledge include any knowledge, techniques, experience and Know-How to
the extent (at any time, for such time) within the scope of any issued, valid
and enforceable patent claim Controlled by the Disclosing Party.
1.165. “Responsible Party” has the meaning set forth in Section 3.1.6(a).
1.166. “Royalty Term” means, with respect to any particular Licensed Product in
any particular country in the Territory, the period (a) commencing, on a
country-by-country and Licensed Product-by-Licensed Product basis, on the First
Commercial Sale of such Licensed Product in such country and (b) expiring on the
date of the earlier of (x) the *** anniversary of the First Commercial Sale of
such Licensed Product in a country, and (y) the commencement of the *** Profit
Share Term, *** Profit Share Term ***. For the avoidance of doubt, the Royalty
Term for a given Licensed Product in a given country in the Territory, if not
previously expired, will expire immediately upon expiration or termination of
this Agreement. On a Licensed Product-by-Licensed Product and country-by-country
basis, the royalty rates for the Royalty Term *** within such country.
1.167. “Safety Stock” has the meaning set forth in Section 3.8.3.
1.168. “sBLA” has the meaning set forth in Section 3.10.3(a).
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1.169. “Site” has the meaning set forth in Section 4.2.1(b).
1.170. “SOPs” has the meaning set forth in Section 4.1.
1.171. “Specimens” has the meaning set forth in Section 4.6.
1.172. “Statistical Analysis Plan” has the meaning set forth in Section 4.5.6.
1.173. “Subject” has the meaning set forth in Section 4.3.2.
1.174. “Subject Recruitment Plan” has the meaning set forth in Section 4.3.1.
1.175. “Supply Agreement” has the meaning set forth in Section 3.6.2.
1.176. “Term” has the meaning set forth in Section 9.1.
1.177. “***” has the meaning set forth in Section 9.5.1.
1.178. “Territory” means all countries of the world other than countries in any
*** that have been terminated under this Agreement pursuant to Article 9. For
clarity, Territory includes each of the remaining *** under this Agreement
(which until the termination of a ***, includes ***).
1.179. “Third Party” means any Person other than Pfizer, OPKO or their
respective Affiliates.
1.180. “Third Party Claim” has the meaning set forth in Section 10.4.1.
1.181. “Third Party Infringement” has the meaning set forth in Section 6.4.1.
1.182. “Trademark” means any trademark, trade name, service mark, service name,
brand, domain name, trade dress, logo, slogan or other indicia of origin or
ownership, including the goodwill and activities associated with each of the
foregoing.
1.183. “Transition Plan” has the meaning set forth in Section 2.8.1.
1.184. “Treaty” has the meaning set forth in Section 5.7.1.
1.185. “Trial” means all clinical trials, including methodology and
non-interventional trials, whether initiated prior to or following the Original
Execution Date, to be conducted pursuant to the Development Plan.
1.186. “Trial Database” has the meaning set forth in Section 4.5.3(a).
1.187. “Trial Master File” has the meaning set forth in Section 4.5.4.
1.188. “United States” or “U.S.” means the United States of America and all its
territories and possessions. For clarity, the United States of America includes
Puerto Rico.
1.189. “Upfront Payment” has the meaning set forth in Section 5.1.
1.190. “***” means the *** comprised of the ***.
1.191. “***” means that period beginning on the *** and ending on termination of
this Agreement in its entirety ***.
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1.192. “U.S. Regulatory Approval” means the first achievement of Regulatory
Approval of a BLA for a Licensed Product for an Approved Indication.
1.193. “Valid Claim” means, with respect to a particular country, a claim of a
Licensed Patent Right that: (a) is (i) issued or, (ii) as to a claim in a
pending patent application which claim was filed in good faith, has been pending
for a period of *** years or fewer from its first office action; (b) has not
been held permanently revoked, unenforceable or invalid by a decision of a court
or other Governmental Authority of competent jurisdiction, which decision is
unappealable or unappealed within the time allowed for appeal; and (c) has not
expired or been cancelled, withdrawn, abandoned, disclaimed or admitted to be
invalid or unenforceable through reissue, disclaimer or otherwise. For clarity,
any pending claim in an application in any country that has not been granted
within *** years from its first office action shall not be included as a Valid
Claim until such claim is granted and the provisions of (b) and (c) above are
satisfied.
1.194. “VAT” has the meaning set forth in Section 5.7.1.
1.195. “Vendor” means any Third Party with whom a Party may contract for the
procurement of services, equipment, tools, materials and/or supplies.
1.196. “Vendor Agreement” has the meaning set forth in Section 3.1.11(b).
1.197. “Vendor Oversight Plan” has the meaning set forth in Section 4.8.
1.198. Interpretation. Except where the context expressly requires otherwise,
(a) the use of any gender herein shall be deemed to encompass references to
either or both genders, and the use of the singular shall be deemed to include
the plural (and vice versa), (b) the words “include”, “includes” and “including”
shall be deemed to be followed by the phrase “without limitation”, (c) the word
“will” shall be construed to have the same meaning and effect as the word
“shall”, (d) any definition of or reference to any agreement, instrument or
other document herein shall be construed as referring to such agreement,
instrument or 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), (e) any reference herein to any Person shall
be construed to include the Person’s successors and assigns, (f) the words
“herein”, “hereof” and “hereunder”, and words of similar import, shall be
construed to refer to this Agreement in its entirety and not to any particular
provision hereof, (g) the word “days” shall mean calendar days, (h) all
references herein to Articles, Sections, Exhibits or Schedules shall be
construed to refer to Articles, Sections, Exhibits or Schedules of this
Agreement, and references to this Agreement include all Exhibits and Schedules
hereto, (i) the word “notice” means notice in writing (whether or not
specifically stated) and shall include notices, consents, approvals and other
written communications contemplated under this Agreement, (j) provisions that
require that a Party, the Parties or any committee hereunder “agree,” “consent”
or “approve” or the like shall require that such agreement, consent or approval
be specific and in writing, whether by written agreement, letter, approved
minutes or otherwise (but excluding e-mail and instant messaging), (k)
references to any specific law, rule or regulation, or article, section or other
division thereof, shall be deemed to include the then-current amendments thereto
or any replacement or successor law, rule or regulation thereof, and (l) the
term “or” shall be interpreted in the inclusive sense commonly associated with
the term “and/or” unless the context dictates otherwise because the subjects of
the conjunction are mutually exclusive.
2. LICENSES.
2.1. Exclusive License Grant. Subject to the terms of this Agreement, including
Section 2.2 and Article 4, as of the Original Effective Date, OPKO hereby grants
to Pfizer an
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exclusive royalty-bearing license (even as to OPKO and its Affiliates) under the
Licensed Technology to use, have used, Develop, have Developed, Manufacture,
have Manufactured, Commercialize, and have Commercialized Compounds and Licensed
Products in the Territory.
2.2. Non-Exclusive Grant-Back License. Subject to the terms of this Agreement,
as of the Original Effective Date, Pfizer hereby grants to OPKO and its
Affiliates a fully-paid non-exclusive sublicense, with the right to sublicense,
under the Licensed Technology and Pfizer’s rights in any Pfizer Developed IP to
Develop and have Developed Compounds and Licensed Products (including any Device
used with or that accompanies Licensed Products) in the Territory, solely to the
extent necessary for performance by OPKO of its obligations pursuant to Section
2.8 and Articles 3 and 4 of this Agreement. The foregoing sublicense is further
sublicenseable to the extent useful or reasonably necessary for OPKO to fulfill
its obligations hereunder.
2.3. Sublicenses for Pfizer Development and Commercialization.
2.3.1. Pfizer may not sublicense the rights granted under Section 2.1 in whole
or in part without the prior written consent of OPKO; provided, however, that
Pfizer may, subject to the requirements of this Section 2.3, without the prior
written consent of OPKO:
(a) ***
(b) ***
In the event that Pfizer or its Affiliates need to grant a sublicense reasonably
required for Pfizer to perform its obligations under this Agreement in
connection with the Development, Manufacture and Commercialization of Licensed
Products throughout the Territory, and the sublicense is not specifically
permitted under Sections 2.3.1(a) or 2.3.1(b), then OPKO agrees to not
unreasonably withhold its consent to such sublicense.
2.3.2. With respect to a permitted sublicense, (i) the relevant Third Party
sublicensee(s) must be reasonably capable of assisting Pfizer in exploiting the
market opportunity in the Territory for the Licensed Product based on the
Development planned for the Licensed Product at the time of sublicense and must
agree in writing to assume Pfizer’s obligations with respect to the Licensed
Product hereunder, (ii) Pfizer shall provide OPKO not less than *** days’ prior
written notice of such sublicense and shall promptly respond to any reasonable
inquiries by OPKO with respect thereto, and (iii) Pfizer shall provide to OPKO
no fewer than *** days after execution a copy of each such sublicense, provided
that Pfizer may redact confidential information from such sublicense agreement
that is not reasonably necessary to demonstrate Pfizer’s compliance with the
obligations set forth in this Section 2.3. Notwithstanding anything to the
contrary, the prior written consent of OPKO shall be required for sublicenses to
any Third Party that includes a right of Commercialization of any or all of the
Major Market Countries.
2.3.3. Pfizer shall remain fully responsible to OPKO for the performance of all
such permitted sublicensees, including if it has delegated Development,
Manufacturing or Commercialization activities to, or otherwise contracted with,
a Third Party Manufacturer, as if Pfizer had not so delegated and/or contracted
with respect to such responsibilities. Sublicensees shall not have a right to
further sublicense other than to their Affiliates. Pfizer shall not have any
rights to grant any sublicenses under the Licensed Technology except as
otherwise granted in this Section 2.3.
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2.4. Licenses to Pfizer Developed IP. To the extent any of the Pfizer Developed
IP relates to or is directed to CTP Technology or any derivatives, variants or
improvements thereof (such Intellectual Property Rights, collectively, the
“Pfizer Developed CTP IP”) and is useful outside of its use in connection with
the Licensed Products, then upon the request of OPKO and subject to the terms
and conditions of this Agreement, Pfizer and OPKO shall negotiate in good faith
to seek to agree upon commercially reasonable terms for an exclusive or
non-exclusive (at the option of OPKO) licensing arrangement with respect to such
Pfizer Developed CTP IP; provided that neither Party will have any obligation to
enter into any such licensing arrangement.
2.5. Direct Licenses to Affiliates. Pfizer may, from time to time, request that
OPKO grant licenses directly to Affiliates of Pfizer by giving written notice,
upon receipt of which OPKO agrees to enter into and sign a separate direct
license agreement with such designated Affiliate of Pfizer. All such direct
license agreements shall be consistent with the terms and conditions of this
Agreement, except for such modifications as may be required by Applicable Laws
in the country in which the direct license will be exercised. The Parties
further agree to make such amendments to this Agreement that are necessary to
conform the combined terms of such direct licenses and this Agreement to the
terms of this Agreement. All costs of making such direct license agreement(s),
including OPKO’s reasonable attorneys’ fees, under this Section 2.5 shall be
borne by Pfizer.
2.6. Right of Reference. OPKO hereby grants to Pfizer a “Right of Reference,” as
that term is defined in 21 C.F.R. § 314.3(b) (or any analogous Applicable Law
recognized outside of the United States), to all data Controlled by OPKO or its
Affiliates that relates to any Compound or Licensed Product, and OPKO shall
provide a signed statement to this effect, if requested by Pfizer, in accordance
with 21 C.F.R. § 314.50(g)(3) (or any analogous Applicable Law recognized
outside of the United States).
2.7. No Implied Rights; Retained Rights. Except as expressly provided in this
Agreement, neither Party shall be deemed to have granted the other Party (by
implication, estoppel or otherwise) any right, title, license or other interest
in or with respect to any Intellectual Property Rights or information Controlled
by such Party. For the avoidance of doubt, OPKO retains the right to use the
Licensed Technology in order to use, have used, Develop, have Developed,
Manufacture, have Manufactured, Commercialize, and have Commercialized products
other than Licensed Products, on its own or with any other party throughout the
world, and to use, have used, Develop, have Developed, Manufacture, have
Manufactured, Commercialize and have Commercialized products incorporating the
CTP Technology in connection with any polypeptide or other compound which is not
a Compound.
2.8. Transfer Activities.
2.8.1. Transition Plan. OPKO shall cooperate with and provide timely assistance
to Pfizer to ensure the smooth transition and to facilitate the transfer of the
Licensed Technology to Pfizer, including taking the actions specified in a
transition plan to be agreed by the Parties (the “Transition Plan”). If there is
an inconsistency between the Transition Plan and this Agreement, the terms of
this Agreement shall prevail.
2.8.2. Initial Disclosure and Knowledge Transfer. As soon as reasonably
possible, *** after the Original Effective Date, OPKO shall *** transfer to
Pfizer true, accurate and complete copies of all Licensed Know-How and material
documentation related to Licensed Patent Rights, in each case to the extent
developed by OPKO on or prior to the Original Effective Date, by download of
digital files to a secure website or e-room designated and controlled by Pfizer.
To the extent that any material Licensed Know-How *** as of the Original
Effective Date, OPKO shall have *** such Licensed
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Know-How in a reasonably organized and complete form, and *** to Pfizer. Such
Licensed Know-How shall include information to assist Pfizer to develop
processes and procedures, including training, to Manufacture the ***.
2.8.3. Continuing Disclosure and Knowledge Transfer. On a ***, or more
frequently at the reasonable request of a Party during the Term, each Party
shall provide the JDC a written summary of all Know-How and Patent Rights that
it develops to the extent such Know-How and/or Patent Rights are or are to be
licensed or assigned to the other Party. During the Term, each Party shall make
appropriate personnel available to the other Party at reasonable times and
places and upon reasonable prior notice for the purpose of assisting the other
Party to understand and use such Know-How and Patent Rights.
3. DEVELOPMENT AND COMMERCIALIZATION.
3.1. Development.
3.1.1. Development Plan.
(a) Generally. Subject to the terms and conditions of this Agreement, each of
OPKO and Pfizer shall Develop Licensed Products in accordance with the amended
and restated development plan attached hereto as Exhibit A (as the same may be
further amended from time to time in accordance with Section 3.1.8, the
“Development Plan”). The Development Plan, which is effective as of the
Amendment Effective Date, replaces, in its entirety, the former Development Plan
attached to the Agreement at the Original Execution Date, as such Development
Plan may have been amended prior to the Amendment Effective Date.
(b) Development Activities for PGHD. The Parties acknowledge and agree that, as
further set forth in the Development Plan and to the extent relating to the
Development of Licensed Products for PGHD, OPKO will be responsible for
conducting all activities, including all clinical and associated regulatory
activities, as set forth in the Development Plan, subject to oversight by the
JDC; provided, however, that, notwithstanding the foregoing, Pfizer will be
responsible for (i) conducting ***, as set forth in the Development Plan,
(ii) conducting the CMC Activities, including the Licensed Product CMC
Activities and ***, as set forth in the Development Plan, (iii) supplying
Licensed Product and Genotropin to OPKO for use in connection with OPKO
conducting its activities under the Development Plan, as may be set forth in the
Supply Agreement and the Quality Agreement and (iv) preparing, seeking,
submitting and maintaining all regulatory filings for the BLA and all subsequent
supplemental filings and Regulatory Approvals for all Compounds and Licensed
Products as further set forth in Section 3.3. Further, notwithstanding any
provision of this Agreement to the contrary, (A) *** over (1) all regulatory
submissions and decisions in connection with any Trial for which it is serving
as regulatory sponsor in accordance with the Development Plan, and (2) all
regulatory submissions and decisions for the BLA and all subsequent supplemental
filings and Regulatory Approvals for all Compounds and Licensed Products in
accordance with Section 3.3, and (B) *** shall have sole control over all
regulatory submissions and decisions in connection with any Trial for which it
is serving as regulatory sponsor in accordance with the Development Plan.
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3.1.2. Allocation of Costs and Expenses for PGHD. As between the Parties, the
following costs for the Development of Licensed Products for PGHD shall be
allocated as follows:
(a) Pre-Amendment Effective Date Period. Subject to the remainder of this
Section 3.1.2, Pfizer and OPKO hereby acknowledge that, as of the Amendment
Execution Date, Pfizer has invoiced OPKO for all costs and expenses incurred by
Pfizer prior to the Amendment Effective Date with respect to the Development of
Licensed Products under the Development Plan for which OPKO is responsible and
OPKO has paid for all such costs and expenses.
(a) Post-Amendment Effective Date Period. Subject to the remainder of this
Section 3.1.2, with respect to the period of time occurring after the Amendment
Effective Date (the “Post-Amendment Effective Date Period”), the Parties shall
equally share all costs (including costs incurred by Pfizer in conducting the
Manufacturing Activities as set forth in Section 3.1.2(f)) of Developing a
Licensed Product for PGHD in accordance with the Development Plan;
(b) Post-Marketing Commitments. Subject to the remainder of this Section 3.1.2,
following the Post-Amendment Effective Date Period, the Parties shall equally
share all costs of conducting any *** for a Licensed Product for PGHD ***;
(c) ***. Notwithstanding any provisions of this Section 3.1.2 to the contrary,
the Parties shall equally share all costs of *** in accordance with the
Development Plan, including all costs of the ***;
(d) ***. The Parties shall equally share all costs associated with conducting
the *** in accordance with the Development Plan;
(a) Manufacturing Activities.
(i) Division of Manufacturing Activity Costs. With respect to Developing a
Licensed Product for PGHD in accordance with the Development Plan, all costs
incurred by Pfizer during the Post-Amendment Effective Date Period in connection
with Pfizer (A) *** for use by OPKO in connection with conducting its activities
under the Development Plan and (B) *** ((A) and (B) collectively, the
“Manufacturing Activities”), shall be equally shared by the Parties.
(ii) Calculation of Manufacturing Activity Costs. Pfizer shall calculate its
costs incurred in conducting the Manufacturing Activities as follows (A)
Licensed Products will be supplied by Pfizer in connection with the Development
Plan and Development Budget *** and (B) the Licensed Product CMC Activities
shall be provided at ***; provided that in no event shall OPKO be obligated to
*** for such activities.
(b) Costs to be Reimbursed to Pfizer. The Parties shall equally share all costs
incurred by Pfizer in connection with ***.
3.1.3. Allocation of Costs and Expenses for AGHD. As more fully set forth in
Section 3.10.3(a), the Parties *** in preparing and submitting a sBLA for a
Licensed
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Product for AGHD in the United States; provided that, *** (which ***) for
inclusion in such submission.
3.1.4. Allocation of Costs and Expenses for Additional Pediatric Indication. As
more fully set forth in Section 3.10.3(b), if the JDC approves an amended
Development Plan and corresponding amended Development Budget for the Additional
Pediatric Indication, then the costs of Developing such Licensed Product for the
Additional Pediatric Indication shall be shared equally by the Parties.
3.1.5. Estimated Budget. The amended and restated budget attached hereto as
Exhibit B sets forth the cost anticipated to be incurred in connection with the
implementation of the Development Plan (the “Development Budget”), and replaces,
in its entirety, the former Development Budget attached to the Agreement at the
Original Execution Date, as such Development Budget may have been amended prior
to the Amendment Effective Date. The Parties acknowledge and agree that (a) ***
and (b) the Development Budget *** under Section 3.1.2 or Section 3.10.3, except
as expressly set forth therein. The Parties shall update the Development Budget
as necessary based on any amendments to the Development Plan approved by the JDC
pursuant to Section 3.1.8.
3.1.6. Invoicing and Payments.
(a) Invoicing. No later than *** after the end of each Calendar Quarter during
which a Party (the “Invoicing Party”) has incurred any costs that are the
responsibility of the other Party under Section 3.1.2 or, to the extent
applicable, Section 3.10.3 (the “Responsible Party”), the Invoicing Party shall
submit to the Responsible Party an invoice setting forth the amounts (or the
portion of such amounts, as applicable) for which the Responsible Party is
responsible. Each invoice shall be accompanied with reasonable supporting
explanation for such invoiced amounts. The Responsible Party shall pay all
undisputed amounts invoiced within *** of receipt of such invoice. Any
adjustments with respect to any previously submitted invoice by the Invoicing
Party shall be reflected in the next such invoice delivered by the Invoicing
Party to the Responsible Party, such adjustments to be made in a manner
consistent with the internal accounting policies of the Invoicing Party. At the
end of each Calendar Quarter, or as otherwise agreed by the JDC, each Party
shall submit to the JDC a report setting forth the status of the costs and
expenses incurred by the Party in respect of its activities under the
Development Plan in comparison to the related budget for such activities as set
forth in the Development Budget.
(b) Invoice Disputes. If a Party reasonably and in good faith disputes any
invoice (or portion thereof) submitted by the other Party, then the disputing
Party shall notify the Invoicing Party in writing of such dispute within *** of
the disputing Party’s receipt of the relevant invoice and the disputing Party
shall only be obligated to pay to the Invoicing Party the undisputed portion of
such invoice. A written notice of dispute may also include a request for any
additional information or supporting documentation that the disputing Party
reasonably and in good faith believes is necessary to determine whether it is
responsible for the invoiced amounts. The Invoicing Party shall reasonably and
in good faith respond to such request in writing within *** of receipt thereof
with the requested information and documentation or an explanation as to why
such requested information and documentation is not available. The Parties shall
resolve such payment dispute in accordance with the dispute resolution
provisions set forth in
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Sections 11.13 and 11.14. If, following final resolution of such dispute, it is
determined that the disputed amounts were properly owed to the Invoicing Party,
then the disputing Party shall pay such disputed amounts (plus interest
calculated pursuant to Section 3.1.6(c)) to the invoicing Party within *** of
final resolution of such dispute.
(c) Interest. With respect to amounts due under Section 3.1.6(a) that are not
paid when due, such amounts shall accrue interest (i) if such amount is *** past
due, at a rate equal to the thirty (30) day U.S. Dollar *** and (ii) if such
amount is more than *** past due, at a rate equal to the thirty (30) day U.S.
Dollar ***.
3.1.7. Payment ***.
(a) Funding of ***; Withdrawals. Subject to the balance of this Section 3.1.7,
if, *** (or portion thereof) delivered by Pfizer in accordance with
Section 3.1.6(a), then upon the written request of Pfizer, ***. If OPKO fails to
pay Pfizer for any undisputed invoice (or portion thereof) within *** days of
OPKO’s receipt of such invoice as set forth in Section 3.1.6(a), then (i) (A) if
the *** Pfizer may upon written notice to OPKO *** which amount shall bear
interest in accordance with Section 3.1.6(c) through the date *** and (B)
following any *** and receipt of written notice from Pfizer of such ***, then,
consistent with the first sentence of this Section 3.1.7(a), the *** to Pfizer
and, *** Pfizer’s and OPKO’s rights and responsibilities with respect to *** and
payment shall be as set forth in subclause (i) hereof. Upon Pfizer’s receipt of
any payment from *** for amounts *** pursuant to this Section 3.1.7(a), Pfizer
shall ***.
(b) Remittance of ***. Within sixty (60) days following ***, if any.
3.1.8. Changes to the Development Plan. During the Term, any changes or other
amendments to the Development Plan (excluding any country-specific appendices
required by Applicable Laws or any changes made in response to any
communications with any Regulatory Authorities that require a submission to a
Regulatory Authority, an IRB or other ethics committee, each of which shall be
added to and implemented in the Development Plan in accordance with Applicable
Law or instructions from Regulatory Authorities, as applicable) shall require
the JDC’s approval, subject to the tie-breaking provisions and limitations on
tie-breaking authority set forth in Section 3.2.5. If the JDC agrees to change
or otherwise amend the Development Plan so that a Party shall perform new
Development or Manufacturing activities, then the Parties shall meet and
discuss, in good faith, an appropriate allocation of costs with respect to such
activities and shall amend the Development Budget to reflect the agreed to
allocation of costs.
3.1.9. Approvals Under the Development Plan. Each Party will be responsible for
obtaining all necessary Regulatory Approvals or other approvals as may be
required for the implementation of those parts of the Development Plan allocated
to them as their responsibility (including as required by Applicable Law) prior
to commencing any Trial, and each Party will reasonably cooperate with the other
Party in such regard.
3.1.10. Sponsor.
(a) Sponsorship and Responsibilities. During the Term for the Development of the
Licensed Product for PGHD, OPKO will be the regulatory
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sponsor of a Trial in all countries in the Territory where any Trial is
conducted as specified in the Development Plan, except (i) to the extent that
the JDC has determined that Pfizer should be the regulatory sponsor or (ii) with
respect to the *** in which case Pfizer will be such regulatory sponsor, and
except as otherwise provided herein, OPKO (or Pfizer where relevant) will have
all responsibilities of such regulatory sponsor as specified under Applicable
Laws and OPKO and Pfizer will have such other responsibilities as are described
in the Development Plan.
(b) Compliance with the Development Plan and Applicable Laws. During the Term,
OPKO shall use Commercially Reasonable Efforts to perform its obligations under
the Development Plan and this Agreement in compliance with all Applicable Laws
and obligations imposed by any Regulatory Authorities (including GCP) and the
terms of this Agreement. During the Term, Pfizer shall use Commercially
Reasonable Efforts to perform its obligations under this Agreement in compliance
with all Applicable Laws and obligations imposed by any Regulatory Authorities
(including GCP) and the terms of this Agreement.
3.1.11. Approved CROs and Approved Vendors.
(a) Approved CROs. Except as otherwise provided herein, OPKO may delegate any of
its responsibilities described in Section 3.1.10 to one (1) or more CROs
determined by the JDC (an “Approved CRO”) pursuant to a written agreement
between OPKO and such Approved CRO (a “CRO Agreement”). Each CRO Agreement will
enable OPKO to comply with the terms hereof, including, but not limited to, in
respect of Section 3.1.10(b), the terms pertaining to ownership of intellectual
property and publications and treatment of Confidential Information.
(b) Approved Vendors. Except as otherwise provided herein, OPKO will be
permitted to contract with one or more Vendors determined by the JDC (an
“Approved Vendor”) pursuant to a written agreement between OPKO and such
Approved Vendor (a “Vendor Agreement”). Each Vendor Agreement will enable OPKO
to comply with the terms hereof, including, but not limited to, in respect of
Section 3.1.10(b), the terms pertaining to ownership of intellectual property
and publications and treatment of Confidential Information.
(c) Responsibility. For clarity, OPKO will remain responsible for all its
obligations under this Agreement, including if it has delegated such to an
Approved CRO and/or contracted with an Approved Vendor (except to the extent any
Vendor Agreement has been assigned to Pfizer or a Third Party designee of
Pfizer), as if OPKO had not so delegated and/or contracted with respect to such
responsibilities.
(d) Applicability to Pfizer. The terms of this Section 3.1.11 shall also apply
to Pfizer in circumstances where Pfizer is a regulatory sponsor of a Trial, ***.
3.1.12. Reporting. During the conduct of the Development Plan, at JDC meetings
and as otherwise requested by a Party, each Party shall provide the other Party
with updates in writing with respect to its progress under the Development Plan.
Each such update shall include a summary of activities under the Development
Plan performed by the reporting Party since the previous JDC meeting or request,
including (as applicable) a
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summary of: results, information, and data generated, activities planned with
respect to Development going forward (including updates regarding regulatory
matters and current and future Development or regulatory plans and activities),
challenges anticipated, timeline adjustments, budget updates required by Section
3.1.5 and updates regarding intellectual property issues relating to any
Compound or Licensed Product.
3.1.13. Pfizer Retained Rights. Except for Development activities for which OPKO
is responsible under the Development Plan or as otherwise expressly set forth in
the Development Plan, Pfizer shall have sole authority over and control of the
Development of Compounds and Licensed Product. *** acting in good faith, ***,
then Pfizer shall have the right to provide OPKO with written notice thereof,
including an explanation of the basis for Pfizer’s belief. If OPKO, acting in
good faith, reasonably disputes the contents of Pfizer’s notice, OPKO shall have
the right to deliver to Pfizer a Notice of Dispute within thirty (30) days after
Pfizer’s written notice. Upon Pfizer’s receipt of such Notice of Dispute, the
Parties shall comply with the dispute resolution provisions set forth in
Sections 11.13 and 11.14 ***. If (i) *** (ii) OPKO does not deliver to Pfizer a
Notice of Dispute within thirty (30) days after receipt of Pfizer’s written
notice or (iii) the dispute resolution process results in the confirmation ***
provided that OPKO *** in accordance with Section 3.1.2 or Section 3.10.3.
3.2. Governance of Development Activities; Notifications to the JDC.
3.2.1. Joint Development Committee. The Parties hereby establish a joint
development committee (the “JDC”) to oversee and coordinate the overall conduct
and progress of the activities set forth in the Development Plan. The JDC will
continue to operate during the term of the Development Plan and ***. The JDC
shall provide a forum for sharing the activities conducted, progress against
timelines and results achieved under the Development Plan. Each Party, through
its representatives on the JDC, shall be permitted to provide advice and
commentary with respect to activities performed pursuant to the Development
Plan. The JDC may establish other committees, including a joint manufacturing
committee to oversee activities. Each Party shall take such advice and
commentary into good faith consideration. More specifically, the JDC shall,
subject to the provisions of Section 3.1.8:
(a) oversee, review and coordinate activities and budgets pursuant to the
Development Plan, CMC and supply activities for clinical supply and related
regulatory strategy, including (i) discussing and making suggestions in response
to any notifications described in Section 3.2.4 and (ii) discussing the reports
submitted by each Party to the JDC in accordance with this Agreement and
otherwise monitoring the costs incurred by each Party in the conduct of their
respective activities under the Development Plan;
(b) review and approve amendments and modifications to the Development Plan as
contemplated herein;
(c) exchange and review Development, regulatory, Manufacturing and
Commercialization updates and information, as well as disclosures of developed
intellectual property; and
(d) perform, or delegate to a Party (in the JDC’s discretion), such other duties
as are specifically assigned to the JDC under this Agreement.
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3.2.2. Membership. The JDC shall be composed of *** employees from each of
Pfizer and OPKO (or such other equal number as the Parties may agree) ***. The
JDC shall have at least one (1) representative from each Party with relevant
decision-making authority, such that the JDC is able to effectuate decisions
within the scope of its authority. Any member of the JDC may designate a
substitute to attend JDC meetings upon prior written notice to the other Party.
The chairperson of the JDC shall be an employee of Pfizer (the “Chairperson”).
The Chairperson will be responsible for arranging meetings of the JDC, setting
the agenda for such meetings and organizing and overseeing such meetings. Ad hoc
guests who are subject to written confidentiality obligations commensurate in
scope to the provisions in Section 7.2 may be invited to the JDC meetings, as
mutually agreed, so long as the number of guests is reasonable and does not
disrupt or delay JDC activities. Each Party may replace its JDC members with
other of its employees, at any time, upon written notice to the other Party.
3.2.3. Meetings. During the performance of the Development Plan pursuant to
Section 3.1, the JDC shall meet, in person (at a location mutually agreeable to
the Parties), by teleconference, or by video-teleconference, at least one (1)
time per ***.
3.2.4. Notifications to be Provided to the JDC.
(a) Trial Information. With regard to both New Trials and Existing Trials, OPKO
shall *** summarize for the JDC for its review and input, including status and
any issues related to (i) standard operating procedures, (ii) clinical sites and
investigators, (iii) a subject recruitment plan, (iv) the investigator’s
brochure, (v) case report forms and a data management plan (and compliance
therewith), (vi) an auditing plan, (vii) a monitoring plan (and compliance
therewith), (viii) IND and CTA submissions and approvals, (ix) IRB approvals,
and (x) reporting mechanisms.
(b) Unusual or Unforeseen Events. Each Party will promptly notify the JDC of any
unforeseen or unusual events that occur in connection with the implementation of
the Development Plan, including any events that may affect any of the timelines
set forth therein or that may have a material impact on the success of any BLA
submissions hereunder by Pfizer.
(i) Urgent Safety Measures or Serious Breaches. If either Party becomes aware of
(a) any urgent safety measures taken by a Clinical Investigator to protect
Subjects against any immediate hazard or (b) any serious breaches of the
Development Plan or any Applicable Laws (including GCP guidelines), such Party
will immediately inform the JDC.
(ii) Regulatory Inspections. Each Party will promptly notify the JDC within ***
of any inspection by any Governmental Authority, including any Regulatory
Authority, in connection with Manufacture or any Trial. Each Party will promptly
forward to the JDC copies of any inspection findings relating to Licensed
Product or this Agreement that a Site receives from any Regulatory Authority and
each Party will have a right to comment on any proposed responses related to
such inspections to be made to any Governmental Authorities before such
responses are made.
(iii) Government Investigations. Each Party will promptly notify the JDC upon
learning of any investigations by any Governmental Authority involving any Third
Party conducting activities with respect to
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the Development Plan, including any Approved CRO or Approved Vendor.
(iv) Notification of Error. If either Party learns of an error or omission in
the conduct of the activities under the Development Plan that could call into
question the validity, or otherwise compromise the quality and/or integrity, of
part or all of any of such activities, or other activities conducted in
connection therewith, such Party will inform the JDC in writing within *** hours
of such Party learning of such error and/or omission. The members of the JDC
will discuss in good faith a remediation plan to address such error within ***
days of such written notification. Such remediation plan will not be effective
unless and until approved by the JDC in accordance with Section 3.2.5. If the
JDC approves such remediation plan, the JDC will provide the responsible Party
with written notice thereof, specifying the dates on which, and the detail with
which, such responsible Party will be required to update the JDC of its progress
with respect thereto.
(v) Compliance with Laws. With respect to each of the foregoing Sections
3.2.4(b)(i)-(iv), the Party responsible for notifying the JDC will notify the
Person to whom notice is required to comply with all Applicable Laws.
3.2.5. Decision-Making; Limitations on JDC.
(a) General. Decisions of the JDC shall be made by consensus, with the
representatives of each Party having collectively one (1) vote in all decisions.
Notwithstanding the creation of the JDC, each Party shall retain the rights,
powers and discretion granted to it hereunder, and the JDC shall have only such
rights, powers and discretion as are specifically assigned to it in this
Agreement, and such rights, powers and discretion shall be subject to the terms
and conditions set forth herein. Without limiting the generality of the
foregoing, the JDC shall have no power to amend, modify or waive compliance with
this Agreement, or take any action which, under the terms of this Agreement,
requires the consent or agreement of either or both of the Parties, without
having received such consent or agreement.
(b) Final Decision-Making Authority. In the event that the JDC is unable to
reach a consensus decision on a matter that is within its decision-making
authority within *** Business Days after it has met and used its best efforts to
reach consensus with respect to such decision then, except as expressly provided
to the contrary in this Agreement, including in Sections 3.1.1 and 3.10.3, such
decision shall be made by the representatives of Pfizer unilaterally, and
provided that Pfizer shall not have power to unilaterally resolve a dispute:
***. For all purposes under this Agreement, any decision made pursuant to this
Section 3.2.5 shall be deemed to be the decision of the JDC.
3.3. Regulatory Matters. Except as contemplated by the Development Plan or
pursuant to this Article 3, Pfizer shall have the sole authority over and
control of all regulatory plans and strategies in respect of Compounds and
Licensed Products and will own, have sole authority for, and be responsible for
preparing, seeking, submitting and maintaining all regulatory filings for the
BLA and all subsequent supplemental filings and Regulatory Approvals for all
Compounds and Licensed Products, including preparing all reports necessary as
part of a
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regulatory filing, Regulatory Approval or Regulatory Exclusivity. To the extent
requested by Pfizer from time to time, OPKO shall cooperate with Pfizer and take
such reasonable actions to assist Pfizer in making regulatory filings and
seeking and maintaining Regulatory Approval and Regulatory Exclusivity. With
respect to regulatory activities of OPKO contemplated by the Development Plan:
3.3.1. Communications with Regulatory Authorities. With respect to Trials
conducted by OPKO, OPKO shall promptly provide Pfizer access to a copy of any
written communication received by OPKO or its representatives from any
Regulatory Authority with respect to any Compound or Licensed Product. OPKO will
have primary responsibility to respond to such communications; however, if any
planned written responses or meetings with Regulatory Authorities relates to
information that may affect any of the timelines set forth in the Development
Plan or that may have a material impact on the success of any BLA submission by
Pfizer, then OPKO shall also notify Pfizer in advance of all such responses or
meetings with the Regulatory Authorities, whether in person or by telephone or
videoconference and Pfizer shall be entitled to attend and, if appropriate and
permitted under Applicable Law, participate in all such meetings with Regulatory
Authorities, whether in person or by means of telecommunication; further
provided, however, that where such communications concern the CMC Information,
Pfizer will have primary responsibility to prepare responses to such
communications as described further in this Section 3.3.1. During the
preparation and submission of BLAs, to the extent practical, and provided that
Pfizer will not be required to incur a substantive delay, OPKO shall be provided
with prior notice as reasonably practicable of all proposed communications and
meetings by Pfizer with Regulatory Authorities and afforded the opportunity to
promptly comment on such communications (and Pfizer shall reasonably take into
account such comments) and attend such meetings (unless the Parties shall
reasonably determine that such participation would decrease the likelihood of
obtaining any requisite Regulatory Approval); provided, further, that
notwithstanding anything set forth above, Pfizer will have the sole decision
making authority and responsibility with respect to any such communications and
meetings with Regulatory Authorities. During the preparation and submission of
BLAs, OPKO will provide reasonable support in the preparation of the relevant
sections related to OPKO’s clinical activities (including Modules 1 and 2) and
provide support to the rapid response team for queries. Each Party will promptly
provide the JDC with access to copies of all regulatory communications and, in
circumstances during the Trials conducted by OPKO where such communications
require a response that pertains to the CMC Information, OPKO will provide
Pfizer with a copy of such communication promptly (and in no event more than ***
Business Days) following receipt thereof so that, after having considered any
OPKO comments thereto, at Pfizer’s discretion, Pfizer can provide OPKO with the
relevant response, which OPKO will submit to the applicable Regulatory Authority
in whole without any changes, additions or deletions, except with respect to
translations to local language required by Applicable Law or with Pfizer’s
consent, not to be unreasonably withheld. For clarity, during preparation and
submission of the BLAs, if Pfizer receives any correspondence from any
Regulatory Authorities, including that relates to the CMC Information, Pfizer
will provide OPKO a full and complete copy, of such communication.
3.3.2. Pfizer Approval of Regulatory Filings. During the Trial activities set
out in the Development Plan (other than Trial activities with respect to the
***), OPKO will be the sponsor of all INDs and CTAs and will have responsibility
to submit any report or filing to any Regulatory Authority under such IND or
CTA. However, if any such report or filing includes any information that may
affect any of the timelines set forth in the Development Plan or that may have a
material impact on the success of any BLA
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submissions by Pfizer, OPKO shall provide the JDC with a copy of all such
reports or filings prior to its intended date of submission and the JDC shall
have the right to review, modify and approve all such reports or filings.
3.3.3. INDs and CTAs.
(a) Subject to Section 3.3.4(a) below, OPKO will be responsible for preparing,
submitting and maintaining the INDs and CTAs required by Applicable Law to
conduct each Trial *** and Pfizer will reasonably cooperate with OPKO in such
regard. OPKO will maintain any INDs and CTAs prepared and submitted in
connection with the Trial during the Term until transferred to Pfizer, pursuant
to Section 3.7.
(b) In all countries where the Sites are located, Pfizer will prepare and
provide to OPKO the CMC information required for all INDs and CTAs and any
updates to this information after having considered any OPKO comments thereto.
OPKO will submit the CMC information to the Regulatory Authorities as provided
by Pfizer without any modification thereto, except with respect to translations
to the local language as required by Applicable Law.
3.3.4. Clinical Trial Registries.
(a) Subject to Section 3.6, from and after the Original Effective Date, OPKO
will be responsible, in consultation with Pfizer, for registering, maintaining
and updating any registries pertaining to any Trial *** to the extent required
by any Applicable Laws, including without limiting the foregoing,
www.clinicaltrials.gov, www.clinicalstudyresults.org, and EUDRACT (collectively,
the “Clinical Trial Registries”) in all countries in the Territory.
(b) For clarity, OPKO will ensure that the information on all Clinical Trial
Registries is correct, consistent and in compliance with Applicable Law.
3.3.5. IND. Subject to Section 3.6, OPKO will be responsible for opening and
maintaining the IND and subsequent amendments for Trials *** set out in the
Development Plan.
3.3.6. Regulatory Exclusivity. Pfizer shall use Commercially Reasonable Efforts
to obtain all applicable Regulatory Approvals and Regulatory Exclusivities in
each Major Market Country.
3.4. Cooperation by the Parties.
3.4.1. Generally.
(a) Each Party will, upon request, cooperate with and assist the other Party in
preparing and maintaining any INDs, CTAs and BLAs for the Licensed Product, and
any other submissions and/or communications with the Regulatory Authorities.
Such cooperation will extend to consultation by telephone or at the cooperating
Party’s normal business location and the provision of information Controlled by
a Party, but will not include submissions to any Regulatory Authority for the
other Party. Notwithstanding anything to the contrary herein, each Party will
provide the other Party with reasonable advance notice of any assistance that it
needs in connection with such submissions.
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(b) For clarity, upon Pfizer’s request, OPKO will participate in any meetings
with any Regulatory Authorities in connection with any BLA for the Licensed
Product. In addition, at scheduled time intervals specified in Section 4.12,
OPKO will provide Pfizer with copies of and access to the Clinical Data Package
or portions thereof for use by Pfizer in connection with preparing and
maintaining BLAs for the Licensed Product, and any other submissions and/or
communications with the Regulatory Authorities. Subject to Article 3, Pfizer
will be solely responsible for all such interactions with the Regulatory
Authorities in all countries in the Territory, provided that Pfizer shall
provide OPKO with a copy of any BLA reasonably in advance of filing to enable
OPKO to comment thereon, and Pfizer, at its sole discretion, shall reasonably
take into account such comments.
3.4.2. Clinical Data Package. The “Clinical Data Package” is defined as all
information in OPKO’s possession or control, and all information available
through access provided to Pfizer that can be obtained by OPKO using
Commercially Reasonable Efforts including all non-clinical trial and clinical
trial data that relates to the Development of any Compound or Licensed Product,
including provision of the following to Pfizer by OPKO (a) the definitions and
attributes that comprise the Clinical Data Package, (b) the data quality
management and validation processes that underlie the clinical trials in the
Clinical Data Package and any database in which such Clinical Data Package is
maintained, (c) the methodologies that have been utilized in converting source
data into output (derived) data in connection with the Clinical Data Package,
(d) the relevant statistical analysis assumptions or plans for the clinical
trials in the Clinical Data Package, (e) audit history of the clinical trials in
the Clinical Data Package and the database in which it is maintained, (f) all
data, including appropriately de-identified subject-level records, raw datasets,
compiled data (derived statistical data sets) and trial master files (including
other documentation as determined by Pfizer clinical data management, including
versions of medical coding dictionaries used, statistical programs to produce
tables, listings, and figures, Statistical Analysis Plan, Data Management Plan,
statistical programming plan and other Trial Master File documents) and (g) all
databases, including the safety database and non-clinical and clinical databases
used for development through the clinical trials.
3.4.3. Transfer of the Data Package.
(a) Clinical Datasets. A “Clinical Dataset” is defined as a dataset that
consists of identifier-stripped versions of all study data at the time of
transfer. OPKO will transfer Clinical Datasets in the form of SAS
Export/Transport file format (XPT) files.
(b) Ancillary Documents. In order to make use of the Clinical Datasets, Pfizer
will also need the following ancillary documents, which OPKO will provide, as
they become available, as Portable Document Format (PDF) files:
(i) An electronic data dictionary consisting of all versions of the case report
forms used in the study, annotated with the variable names and corresponding
datasets; and
(ii)  Other documentation as determined by Pfizer clinical data management,
including versions of medical coding dictionaries used, statistical programs to
produce tables/listing/graphs (TLGs), raw and
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derived datasets, SAP, Data Management Plan, statistical programming plan and
other Trial Master File documents.
(c) Test Data Transfer. Within *** months after study initiation, OPKO will
transfer a set of test data to Pfizer. Pfizer will perform certain qualification
steps to determine if the transmission meets Pfizer requirements in content and
process and if the data will load successfully into the target Pfizer database.
OPKO will work with Pfizer if changes are needed in the data formatting or
transmission process to ensure data quality and usability. OPKO will transfer
additional sets of test data if needed after such changes are made and again if
there are any changes in the study variables or data collection tools during the
study.
(d) Data Cleaning and Validation. After each transfer of a Clinical Dataset,
Pfizer and OPKO will collaborate to ensure that the data meets appropriate
quality standards. This may include data queries from Pfizer that OPKO will
investigate and resolve.
(e) Transfer Schedule. The anticipated content and timing of data transfers will
be agreed to by the JDC and documented in a data transfer plan.
3.4.4. Collaboration on Preparations for BLA Regulatory Submissions.

(a) At the request of the JDC, OPKO will provide to Pfizer all information
required for Pfizer to meet its responsibility for BLA/MAA regulatory
submissions including:
(i) Modules M1, M2 or equivalents;
(ii) Integrated Safety Database (mapped to CDISC);
(iii) Pre-inspection Visits and Interviews with OPKO during inspections;
(iv) Rapid response to queries from regulatory authorities;
(v) Clinical Dataset Transfer (test and final transfers); and
(vi) Complete Study Reports for all Phase 1, 2 and 3 Trials.
3.5. Pfizer’s Right to Cross Reference. Upon Pfizer’s written request, OPKO will
provide each applicable Regulatory Authority with a letter of authorization for
each Regulatory Authority to access any submissions of INDs or CTAs to any
Regulatory Authorities made by, or on behalf of, OPKO hereunder in connection
with reviewing any regulatory submission or application to any Regulatory
Authority made by or behalf of Pfizer or any Third Party designated by Pfizer.
3.6. Clinical Supply of Licensed Product; Manufacturing for Clinical Supply.
3.6.1. Supply of Licensed Product; ***; Assignment of *** Agreement. For the
conduct of all Existing Trials and as set forth in the Development Plan, OPKO
shall be responsible for the supply of requisite quantities of Licensed Product.
The Parties acknowledge and agree that OPKO may use *** to supply or have
supplied to OPKO such quantities of Licensed Product. In addition, at any time
that Pfizer may request, OPKO shall assign all of its rights, title and
interests in and to the *** Agreement. In the
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event of such an assignment, Pfizer shall thereafter be responsible for the
supply of requisite quantities of Licensed Product in all Existing Trials.
3.6.2. Pfizer Supply of Licensed Product for Trials. Except as otherwise set
forth in the Development Plan, for the conduct of any Trials initiated following
the Original Execution Date that are conducted by ***, *** will supply or have
supplied to *** such quantities of Licensed Product *** that are necessary for
*** to conduct the activities that it is responsible for under the Development
Plan as provided in (a) a Supply Agreement containing customary terms to be
mutually agreed upon by the Parties (the “Supply Agreement”); provided that all
(i) Licensed Product will be supplied by *** in connection with the Development
Plan and Development Budget *** provided that in no event shall *** for such
Licensed Product and (ii) *** will be supplied by *** at *** and (b) a quality
agreement reasonably acceptable to each Party in form and substance (the
“Quality Agreement”). *** shall also supply Licensed Product and ***. OPKO will
provide the JDC at each JDC meeting with quarterly reports regarding inventory
of Licensed Product and the reasonably anticipated needs for Licensed Product to
ensure that Pfizer can supply OPKO with such quantities of Licensed Product at
such times as required by OPKO to conduct all activities required to be
conducted by OPKO under the Development Plan in compliance with the timelines
set forth therein. For clarity, any use of Licensed Product that is not
described in the Development Plan will be Pfizer’s sole right and responsibility
and OPKO will have no rights or obligations with respect thereto.
3.6.3. Diligence. If Pfizer is responsible for providing clinical supply of
Licensed Product in accordance with Section 3.6.2, Pfizer shall use Commercially
Reasonable Efforts with respect to the Manufacture of such Licensed Product to
permit the Parties to perform their respective Development obligations in the
Development Plan and hereunder without unnecessary expense or delay.
3.6.4. Use of Licensed Product. OPKO will (i) only use Licensed Product supplied
by *** as agreed by the Parties, Pfizer or such Third Parties designated by
Pfizer as a supplier of Licensed Product in connection with conducting
activities under the Development Plan, and (ii) only use Licensed Product, and
provide Licensed Product to permitted Third Party transferees, for the sole
purpose of conducting activities under the Development Plan, and in accordance
with the terms of this Agreement.
3.6.5. Complaints Related to Licensed Product, Devices and/or Compounds. As may
be further set forth in the Supply Agreement and Quality Agreement, each Party
will promptly forward to the JDC any complaints that it receives related to any
Compound, Device or Licensed Product. OPKO shall notify Pfizer if it receives
any complaints that may impact product safety, quality purity and effectiveness
of any Compound, Device or Licensed Product used or to be used in connection
with activities conducted under the Development Plan, including any Trials in
respect thereof, which could result in a product recall. OPKO will respond to
any complaints of which OPKO becomes aware relating to any Compound, Device or
Licensed Product; provided, that Pfizer will provide reasonable cooperation in
connection therewith. Notwithstanding the foregoing, if a complaint pertains to
the Manufacturing, appearance or general physical characteristics of any
Licensed Product or other processes at any Manufacturing facility, Pfizer will
be solely responsible for responding to such complaint.
3.6.6. Recall of Licensed Products Prior to Regulatory Approval. If the Licensed
Product is recalled prior to Regulatory Approval in any jurisdiction in the
Territory, OPKO will be responsible for the operational execution of such recall
in
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connection with the activities it has conducted under the Development Agreement
(but not in connection with Licensed Product being Commercialized by Pfizer or
any other Licensed Product, for which Pfizer will be responsible at its
expense). Pfizer will cooperate with OPKO in connection therewith. The costs for
such a recall will be at Pfizer’s expense, unless such recall and/or costs were
based on the material breach of this Agreement, intentional misconduct, gross
negligence or negligence by OPKO and/or any Third Party conducting activities on
behalf of OPKO, in which case, OPKO will bear the expense of any such recall.
3.7. Regulatory Filings and Other Data.
3.7.1. Transfer of Regulatory Filings and Other Data. At Pfizer’s request
following such time as Regulatory Approval is granted to Pfizer, its Affiliates
and/or sublicensees, for an Approved Indication in AGHD, PGHD or the Additional
Pediatric Indication, for any Licensed Product in the ***, as applicable, or at
such earlier time, as Pfizer may reasonably request, OPKO shall, as permitted
under Applicable Laws, (i) promptly transfer to Pfizer or a designated Affiliate
of Pfizer all such Regulatory Materials and right, title and interest in such
Regulatory Materials, as requested by Pfizer, and (ii) thereafter provide such
support and assistance to Pfizer or such Affiliate in connection with such
matters regarding such Regulatory Materials as may be reasonably requested by
Pfizer or such Affiliate from time to time. OPKO shall provide such Regulatory
Materials in a format reasonably requested by Pfizer or such Affiliate. All
Regulatory Approvals for Licensed Products for which Regulatory Approval has
been granted shall be obtained and held in the name of Pfizer or a designated
Affiliate of Pfizer, and Pfizer or such Affiliate shall maintain all right,
title and interest in and to all such Regulatory Materials.
3.7.2. Submitting and Maintaining Regulatory Approvals. Notwithstanding anything
in this Agreement or the Development Plan to the contrary, Pfizer shall have
sole authority for and be responsible for promptly preparing, seeking, and
submitting and for maintaining all regulatory filings and Regulatory Approvals
for such Licensed Product in such jurisdiction for such Approved Indication. To
the extent requested by Pfizer from time to time, OPKO shall cooperate with
Pfizer and take such reasonable actions to assist Pfizer in making regulatory
filings and maintaining Regulatory Approval for such Licensed Product.
3.8. Commercial Supply of Licensed Product; Manufacturing for Commercial Supply.
3.8.1. Pfizer Supply of Licensed Product. During the Term, Pfizer shall have the
exclusive right to Manufacture Licensed Products for Commercialization itself or
through one or more Affiliates or Third Parties selected by Pfizer in its sole
discretion. Pfizer shall use Commercially Reasonable Efforts with respect to the
Manufacture of Licensed Products as necessary to perform its Commercialization
obligations hereunder.
3.8.2. Capacity. In the event that the materials and/or Manufacturing capacity
required to Manufacture the Licensed Products is not sufficient to meet current
or anticipated demand, Pfizer shall notify OPKO of such shortage and *** meet to
discuss the shortage, including the proposed measures Pfizer intends to take to
address such lack of capacity.
3.8.3. Safety Stock. From and after the Amendment Effective Date, unless
otherwise agreed in writing by the parties, Pfizer shall create and adhere to a
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commercially reasonable plan to maintain an inventory of Licensed Product to
seek to meet anticipated demand (the “Safety Stock”). On a *** basis, Pfizer
shall provide OPKO updates as to the status of the Safety Stock.
3.9. Commercialization Activities.
3.9.1. General. Subject to its diligence obligations, Pfizer shall have sole and
exclusive control over all matters relating to the Commercialization of Licensed
Products, including sole and exclusive control over (a) pricing of Licensed
Products and (b) the negotiation of Licensed Product pricing with Regulatory
Authorities and other Third Parties. *** Pfizer will use Commercially Reasonable
Efforts to seek Regulatory Approval, including Price Approvals, if required, for
Licensed Products in each Major Market Country. *** Pfizer will use Commercially
Reasonable Efforts to Commercialize the Licensed Products in the Major Market
Countries ***.
3.9.2. Branding. Pfizer or its designated Affiliates or sublicensees shall
select and own all Trademarks used in connection with the Commercialization of
any and all Licensed Products. OPKO and its Affiliates shall use Commercially
Reasonable Efforts to not register or use, anywhere in the world, any Trademark
which is confusingly similar to any Trademark used by or on behalf of Pfizer,
its Affiliates or sublicensees in connection with any Licensed Product.
3.9.3. Progress Reporting. During the first *** following the date upon which
the JDC is disbanded pursuant to the provisions of Section 3.2.1, Pfizer shall
provide OPKO with written reports, on the ***, summarizing Pfizer’s activities
to Commercialize Licensed Products and providing any other information as OPKO
might reasonably request regarding the Commercialization of Licensed Products.
Any information or written report provided by Pfizer to OPKO pursuant to this
Section 3.9.3 shall be deemed to be Pfizer’s Confidential Information and
subject to the provisions of Section 7.2. Thereafter, Pfizer shall continue to
provide such reports ***.
3.10. Diligence.
3.10.1. Exceptions to Diligence Obligations. Notwithstanding any provisions of
this Agreement to the contrary: (a) if Pfizer, an Affiliate or sublicensee of
Pfizer, OPKO or a Third Party generates any safety, tolerability or other data
reasonably indicating, as measured by Pfizer’s safety and efficacy evaluation
criteria and methodology, or signaling that a Licensed Product has or would have
an unacceptable risk-benefit profile, Pfizer may take any and all actions it
deems necessary or appropriate in its sole discretion to appropriately address
such concerns, including putting on hold or ceasing Development or
Commercialization of any effected Compound or Licensed Product, or terminating
this Agreement in its entirety; and (b) in such event, Pfizer shall not be in
breach of this Agreement or any obligation hereunder as a result of Pfizer
taking such actions so long as Pfizer is using Commercially Reasonable Efforts
to address and, to the extent practicable, remedy the safety issue in order to
permit continued Commercialization.
3.10.2. Assertion of Pfizer Diligence Obligation Claims. Subject to Section
3.9.1, if OPKO reasonably believes that Pfizer is not using Commercially
Reasonable Efforts with respect to its obligations to Commercialize a Licensed
Product in accordance with this Agreement, then OPKO shall promptly provide to
Pfizer written notice documenting in reasonable detail the reasons for such
assertion. Promptly upon Pfizer’s receipt of any notice of a potential alleged
diligence failure (“Diligence Issue”) pursuant
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to this Section 3.10.2, Pfizer and OPKO will meet and discuss the specific
nature of such Diligence Issue and seek to identify an appropriate corrective
course of action. If, no later than *** days after Pfizer’s receipt of such
notice, (a) the Parties have not reached consensus regarding whether Pfizer has
failed to satisfy its obligations pursuant to Sections 3.8-3.10, and (b) the
Parties have not agreed upon an appropriate corrective course of action for such
Diligence Issue, then such Diligence Issue will be escalated and resolved
pursuant to the provisions set forth in Section 11.13.
3.10.3. Diligence Obligations for Additional Indications.
(a) AGHD. Upon receipt of the first Regulatory Approval (excluding any required
Price Approvals) of a Licensed Product for PGHD in the United States, *** be
required to support the filing and subsequent Regulatory Approval by way of a
supplemental BLA (“sBLA”) for a Licensed Product for AGHD in the United States
and, if the FDA is willing to grant such meeting, attend and participate in such
meeting, and ***. Without limiting the foregoing, ***; provided that *** for
AGHD. In the event that Pfizer determines that it will, or is otherwise required
to, file a sBLA for AGHD in the United States, ***. The Parties *** incurred by
Pfizer in preparing and submitting such sBLA. Except as expressly set forth in
this Section, *** obligation *** unless such additional activities are agreed to
by the Parties in writing, in which case, the *** (unless otherwise agreed to in
writing).
(b) Additional Pediatric Indication.
(i) The Parties shall work together to identify one additional pediatric
indication other than PGHD (the “Additional Pediatric Indication”) ***. If the
Parties are *** on an Additional Pediatric Indication before December 1, 2020,
*** following identification of the Additional Pediatric Indication, *** shall
*** for such Additional Pediatric Indication that ***.
(ii) Promptly following submission to the JDC, the *** Licensed Product for the
Additional Pediatric Indication. In connection therewith, the representatives of
each Party to the JDC shall act reasonably and in good faith.
(iii) *** shall be shared equally by the Parties. Additionally, the Parties
acknowledge and agree that Articles 3 and 4 of this Agreement contemplate that,
except for the ***, OPKO shall be designated as the regulatory sponsor for all
Trials set forth in the Development Plan. If the amended Development Plan
approved by the JDC provides that Pfizer will be designated as the regulatory
sponsor for any Trials set forth in the Development Plan, then such Development
Plan will state Pfizer’s obligations as the regulatory sponsor. Notwithstanding
any provision of this Agreement to the contrary, including any decision-making
authority at the JDC, the amended Development Plan including the Additional
Pediatric Indication shall provide that Pfizer will control the preparation,
submission, pursuit and maintenance of all regulatory filings for the BLA and
all subsequent supplemental filings and Regulatory Approvals for the Licensed
Product for the Additional Pediatric Indication in each Major Market Country.
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(iv) If the *** an amended Development Plan or corresponding amended Development
Budget for the Additional Pediatric Indication (provided Pfizer has complied
with its obligations under Section 3.10.3(b)(i) and Section 3.10.3(b)(ii)), ***.
(v) Notwithstanding any provision of this Agreement to the contrary but in all
cases subject to, and without limitation of, the obligation to act reasonably
and in good faith in accordance with this Section 3.10.3(b), in no event ***.
(a) Expedited Arbitration. Any dispute or disagreement arising between Pfizer
and OPKO in respect of this Section 3.10.3 may be referred by either Party for
resolution through expedited arbitration in accordance with Section 11.14.
3.11. Genotropin Products. Pfizer shall have the exclusive right to Develop,
Manufacture and Commercialize Genotropin Products itself or through one or more
Affiliates or Third Parties selected by Pfizer in its sole discretion. For
clarity, and notwithstanding anything in this Agreement to the contrary, Pfizer
shall have no diligence obligations with respect to the Development, Manufacture
and Commercialization of Genotropin Products. ***.
3.12. Existing Trials. Except as otherwise set forth in the Development Plan,
OPKO shall continue to conduct all Trials initiated prior to the Original
Execution Date (such trials, “Existing Trials”) in accordance with the protocol,
standard operating procedures and other development plans established by OPKO
with respect to such Existing Trials prior to the Original Execution Date,
subject to oversight by the JDC. OPKO shall keep Pfizer apprised of the progress
of all such Existing Trials, engage with Regulatory Authorities, and otherwise
perform its Development obligations as provided for in and in accordance with
this Article 3. OPKO will provide access to all documents and electronic
information currently held by OPKO or OPKO’s CROs and other Vendors, related to
all Existing Trials and any completed Trials, and to facilitate site visits by
Pfizer. OPKO will undertake specific actions requested by Pfizer to remediate
incomplete documentation and make amendments to current SOPs if, in Pfizer’s
opinion, these changes are required to meet regulatory requirements or will have
a material impact on the success of any BLA submissions by Pfizer.
3.13. New Trials. Subject to the terms hereof, OPKO shall (and with respect to
the ***) conduct all Trials initiated following the Original Execution Date
(such trials “New Trials”) in accordance with the protocols, standard operating
procedures and other development plans specified by the JDC and set forth in the
Development Plan or as otherwise approved by the JDC.
3.14. Pharmacovigilance and Safety Information Exchange.
3.14.1. The safety reporting units from each of the Parties will meet and will,
within *** days of the Original Effective Date, agree upon the timing for
establishing a written agreement for exchanging adverse event and other safety
information relating to (a) the Licensed Products, and (b) adverse events
attributable to CTP Technology used in other products (the “Pharmacovigilance
Agreement”). The Pharmacovigilance Agreement will ensure that adverse event and
other safety information is exchanged upon terms that will permit each Party to
comply with Applicable Laws and requirements of Regulatory Authorities. This
Pharmacovigilance Agreement will be established in advance of the earlier of (1)
the first Regulatory Filing in any country in the Territory and
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(2) the start of any clinical trial under an IND or CTA sponsored by Pfizer
related to the Licensed Products.
3.14.2. Following the Original Execution Date and until such time as the
Pharmacovigilance Agreement is executed, within *** Business Days of providing
any notification to the JDC pursuant to Section 3.2.4, the notifying Party shall
provide a copy of such notification to the other Party.
3.14.3. OPKO agrees to manage pharmacovigilance obligations for the Licensed
Products in compliance with global requirements, until such time that these
obligations and all needed legacy data can be transferred to Pfizer, as
established in Section 3.14.1.
3.14.4. OPKO agrees to provide the JDC aggregate clinical safety data relating
to the Licensed Products for the purposes of assessing potential benefit and
risk. The frequency and format for this exchange, including responsible parties,
shall be established by the JDC.
4. TRIAL ACTIVITIES AND RESPONSIBILITIES.
4.1. SOPs. Subject to the terms hereof, for New Trials ***, OPKO will conduct,
or ensure that each Approved CRO conducts, all such New Trials in accordance
with standard operating procedures (the “SOPs”), access to electronic copies of
which will be provided by OPKO to the JDC for review prior to the initiation of
each New Trial at a time to be determined by the JDC. For Existing Trials, OPKO
will provide access to electronic copies of all current SOPs within ninety (90)
days following the Original Effective Date. Pfizer, from time to time, may
request OPKO to make amendments to current SOPs if, in Pfizer’s opinion, these
changes are required to meet regulatory requirements or will have a material
impact on the success of any BLA submission by Pfizer. In the event of any
updates to existing SOPs, or in the event that any Trial *** is not being
conducted in compliance with the SOPs (as updated from time to time), OPKO shall
take all such actions as may be necessary to bring such Trial into compliance
with the then-current SOPs as promptly as is practicable.
4.2. Sites and Clinical Investigations.
4.2.1. Selection of Sites and Investigators.
(a) The JDC will approve the study sites to conduct each Trial *** as proposed
by OPKO.
(b) OPKO will enter, and each Approved CRO will enter, into an agreement with
each study site; such an agreement will be substantially in the form to be
agreed upon by the Parties within *** days following approval by the JDC of the
Development Plan (the “Clinical Trial Agreement”) (upon execution of the
Clinical Trial Agreement, such study site will be deemed a “Site”), and will
provide that any Trial *** may be freely transferred or assigned to Pfizer or a
designee of Pfizer without any negotiation of the CTA necessary. If a study site
requires any material changes to such form Clinical Trial Agreement, OPKO will
inform the JDC and seek JDC approval of such change, and the JDC will not
unreasonably withhold such approval. For clarity, each Clinical Trial Agreement
will specify reasonable terms, consistent with industry standards for similar
agreements, and will expressly require during the period which it is effective
the applicable Site and Clinical Investigator to comply with the terms hereof as
if such Site and Clinical Investigator were a Party hereto, including the terms
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pertaining to ownership of intellectual property and publications, treatment of
Confidential Information and that the Site, the Clinical Investigators and other
personnel working on any Trial at each Site have (i) GCP and other appropriate
training and experience to conduct such Trial(s), including training with
respect to the Development Plan; (ii) access to an adequate number of subjects
that satisfy the criteria in the Development Plan to meet subject enrollment
requirements for such Trial(s); (iii) any licenses, certifications and/or
accreditations required by Applicable Laws; and (iv) understand the Development
Plan and their obligation to comply therewith and all Applicable Laws in
conducting such Trial(s). Any such representations and warranties will be made
for the benefit of OPKO and Pfizer as third party beneficiaries.
(c) The Clinical Trials Agreements will also provide that the Clinical
Investigators, any sub-investigators (e.g., research fellows, residents and
associates) and any others required by Applicable Law at each Site complete the
financial disclosure document with respect to Pfizer and OPKO, and such
financial disclosure document will be substantially in the form to be agreed
upon by the Parties within *** days following approval by the JDC of the final
Development Plan (the “Financial Disclosure Form”). For clarity, if any of the
foregoing individuals do not complete such Financial Disclosure Form, such
individuals may not participate in, or do any work in connection with, any
Trial.
4.2.2. Obligations During Trial Conduct.
(a) From and after the Original Effective Date, OPKO will conduct meetings with
the Clinical Investigators (each, a “Clinical Investigator Meeting”), of which
the JDC will be provided with reasonable advance notice and in which Pfizer will
have the right (but not the obligation) to attend and participate (at Pfizer’s
cost). Minutes of Clinical Investigator Meetings will be made available to the
JDC upon request.
(b) OPKO will provide the JDC with copies of all communications relevant to any
Trial *** and provided to all Sites, and upon request of the JDC, provide the
JDC with copies of any other communications between OPKO and any individual
Sites and/or any Affiliate or Approved CRO and any individual Sites.
(c) If OPKO terminates a Site, OPKO will inform the JDC with the reason for such
termination and if reasonably practicable, such notice will be provided
reasonably in advance of such termination.
(d) OPKO will meet its CRO Trial Site Monitoring and Vendor Oversight
responsibilities as established by the JDC as specified in Section 4.8.
4.3. Subjects and Informed Consent.
4.3.1. Subject Recruitment Plan. OPKO will comply with the subject recruitment
plan for each Trial ***, which will be established by OPKO and communicated to
the JDC, for approval by the JDC not to be unreasonably withheld, within a
reasonable period of time after the Original Effective Date not to exceed ninety
(90) days (the “Subject Recruitment Plan”) in recruiting subjects to participate
in such Trial. For clarity, prior to engaging in any recruiting activities, OPKO
will ensure that the
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applicable IRBs and/or other ethics committees approve any related materials and
activities as required by the JDC and all Applicable Laws.
4.3.2. Informed Consent. OPKO will prepare the informed consent document for use
in each Trial ***. OPKO will ensure that the informed consent of each subject
participating in any Trial be obtained in accordance with all Applicable Laws,
including completion of the informed consent document; such informed consent
document for such Trial will be substantially in the form to be agreed upon by
the Parties within *** days following approval by the JDC of the Development
Plan (collectively, “Informed Consent”) (upon obtaining such Informed Consent, a
prospective subject will be deemed a “Subject”). For clarity, the Informed
Consent document that each Subject signs will expressly state that each Subject
understands that Pfizer is providing support for such Trial and will authorize
disclosure of data and results related to such Trial to Pfizer for any purpose,
subject to all Applicable Laws. For clarity, OPKO will be required to obtain
Pfizer’s prior written consent (which shall not be unreasonably withheld) for
any subsequent material amendments to the form initially agreed upon by the
Parties or for translations of such form.
4.3.3. Inclusion and Exclusion Criteria. Neither OPKO nor any of its
Representatives will provide a waiver for any exclusion or inclusion criteria
related to a Trial *** as specified in the Development Plan. Any changes to the
exclusion or inclusion criteria will be subject to an amendment to the
Development Plan to be approved by the JDC pursuant to the terms of this
Agreement.
4.4. Investigator’s Brochure. OPKO will prepare and maintain the investigator’s
brochure for the Licensed Products. OPKO will, promptly following receipt of
written notice from Pfizer of the need for the most recent version of the
investigator’s brochure, provide Pfizer with such version of the investigator’s
brochure.
4.5. Data Collection and Data Management.
4.5.1. CRF. From and after the Original Effective Date, OPKO will be responsible
for preparing the CRF for each Trial *** in accordance with the Development
Plan. OPKO will provide the JDC with access to electronic copies of the CRFs for
review by the JDC. A CRF is to be completed for each Subject and will be in
electronic form, validated and in compliance with all Applicable Laws.
4.5.2. Data Management Plan.
(a) OPKO will comply with the data management plan to be agreed upon by the
Parties within *** Business Days following approval by the JDC of the
Development Plan (the “Data Management Plan”). For clarity, the Data Management
Plan will provide Pfizer the right to review the Development Plan, and OPKO will
agree to make modifications requested by Pfizer if they are considered by Pfizer
to affect any of the timelines set forth in the Development Plan or may have a
material impact on the success of any BLA submissions hereunder by Pfizer. The
Data Management Plan will be agreed upon by the Parties prior to recruitment of
Subjects for any future Trial.
(b) During the Term, with respect to any data collected in connection with any
Trial, OPKO will ensure that such data is held in one or more appropriate
facilities with information security protections (including in accordance with
all Applicable Laws) including: (i) unique accounts for all
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operators; (ii) cancellation of an account when an employee or other personnel
terminates employment; (iii) deactivation of an account when an employee or
other personnel ceases working on the Trial; (iv) required password changes at
frequent intervals; and (v) regular backups of electronic data.
4.5.3. Trial Database.
(a) OPKO will promptly update the applicable trial database for the data
collected from each Site for each Trial *** (each, a “Trial Database”) upon
receiving data for any such Trial from any Site, and OPKO will ensure that the
Sites, promptly following receipt thereof, provide data in connection with such
Trial to OPKO.
(b) OPKO will provide the JDC with access to electronic copies of such data
requested by the JDC at JDC meetings and in accordance with Applicable Laws.
(c) If, at any time following the Original Effective Date, OPKO decides to
change the format of the database for any such Trial, OPKO will so notify Pfizer
and the Parties will cooperate to ensure that the format that OPKO selects
permits Pfizer to incorporate the data from such Trial into its relevant systems
and is in compliance with all Applicable Laws.
(d) OPKO will provide SAS datasets to Pfizer in accordance with specifications
as defined by Pfizer in Section 4.12: (i) at such times as Pfizer may reasonably
request such SAS datasets; (ii) if a safety signal is identified; and/or (iii)
if a request is received from any Regulatory Authority.
(e) OPKO will maintain each Trial Database in accordance with all Applicable
Laws, including ensuring that information included in such Trial Database is
accurate and up-to-date.
4.5.4. Trial Master File. Promptly following the Original Effective Date, OPKO
will establish and maintain a trial master file (to the extent they not already
established and maintained for any applicable Trial) for any Trials *** in the
format as agreed upon by the JDC (each a “Trial Master File”). Notwithstanding
anything to the contrary herein, OPKO will not be permitted to delegate its
rights and obligations pursuant to this Section 4.5.4 to any Third Parties
without the prior approval of the JDC, except OPKO may delegate its rights and
obligations pursuant to this Section 4.5.4 to any of its Affiliates provided
that OPKO retains accountability following such delegation.
4.5.5. Source Data Verification. From and after the Original Effective Date,
OPKO will be responsible for source data verification of data records according
to OPKO’s SOPs related to the Monitoring Plan and Vendor Oversight Plan to be
agreed as specified in Section 4.8. At Pfizer’s request, OPKO will provide
Pfizer with copies of any OPKO reports relating to source data verification and
other types of Trial audits.
4.5.6. Statistical Analysis. From and after the Original Effective Date, except
as may otherwise by determined by the mutual agreement of the JDC without
reference to the tie-breaking provisions of Section 3.2.5(b), OPKO will perform
any statistical analysis required in accordance with the statistical analysis
plan for the Trial ***, a draft of which for any applicable Trial will be
attached as an agreement to the Development Plan upon mutual agreement of the
Parties (the “Statistical Analysis Plan”).
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4.6. Specimens. Unless otherwise requested by Pfizer, from and after the
Original Effective Date, OPKO (or its designated CRO) will test, store, or
manage all biological samples and/or associated slides or blocks (collectively,
“Specimens”).
4.7. Audits.
4.7.1. From and after the Original Effective Date, OPKO will conduct quality
oversight inspections and audits of the facilities and services of any CRO or
other applicable Third Parties in accordance with its SOPs and pursuant to a
quality assurance audit plan (the “Auditing Plan”), and OPKO will provide Pfizer
with copies of all audit reports.
4.7.2. Notwithstanding the foregoing, Pfizer will have the right, but not the
obligation, to co-audit with OPKO any sites (including any Sites), facilities
and services of any CRO or other applicable Third Party pursuant to the Auditing
Plan. OPKO will provide the JDC with written notice of any upcoming audits to
enable Pfizer to so participate. If Pfizer chooses to co-audit pursuant to the
foregoing sentence, Pfizer will provide OPKO with advance written notice
thereof, and OPKO will cooperate with Pfizer with respect to such audit. For
clarity, Pfizer’s participation in any auditing activities will not relieve OPKO
of its obligations hereunder and Pfizer will be limited to acting in a
supporting capacity in any such audit.
4.7.3. From and after the Original Effective Date, Pfizer will conduct quality
oversight inspections and audits of the manufacturing facilities for any
Licensed Products in accordance with its internal policies.
4.8. Monitoring and Vendor Oversight. From and after the Original Effective
Date, OPKO will monitor each Trial***, and share information with the JDC
pertaining to monitoring such Trial, in accordance with the monitoring plan for
such Trial to be agreed upon by the Parties within ninety (90) days following
the Original Effective Date (each a “Monitoring Plan”). Within *** days
following the Original Effective Date the Parties also will enter into a vendor
oversight plan mutually agreeable to the Parties (a “Vendor Oversight Plan”).
4.9. IRBs and Other Ethics Committees.
4.9.1. OPKO will be responsible for obtaining the approval of the IRBs and other
ethics committees required prior to commencing, and during, the Trial *** at
every Site.
4.9.2. OPKO will ensure that IRBs and such other relevant ethics committees have
current registrations and accreditations as required by Applicable Law, and OPKO
will provide all ethics committees, including all IRBs, and Regulatory
Authorities, with all necessary documentation prior to, and during the course
of, each Trial *** as required by Applicable Law.
4.9.3. From and after the Original Effective Date, OPKO will be solely
responsible for responding to all queries from the IRBs and other ethics
committees ***; provided that (a) Pfizer will make itself reasonably available
to assist with any such queries, and (b) if such query relates solely to the CMC
Information, Pfizer will prepare the applicable response and provide OPKO with a
copy thereof.
4.9.4. The ultimate responsibility for fulfillment of all pharmacovigilance
obligations resides with the IND or CTA holder and/or the marketing
authorization holder according to relevant Applicable Laws.
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4.10. Independent Data Monitoring Committee (“IDMC”). OPKO will establish an
IDMC for each Trial *** if not already established, which will be governed by a
charter substantially in the form to be agreed upon by the Parties within ***
days of the Original Effective Date (the “IDMC Charter”). For clarity, the IDMC
Charter will specify the number of members of the IDMC, the qualifications of
such members, the experience of the chairman of the IDMC, details regarding open
and closed sessions, including who can attend any such sessions, and information
that the IDMC may share with the Parties, including that efficacy will not be
disclosed to either Party until the IDMC has approved such data. OPKO will
communicate any decision of the IDMC to the JDC within five (5) Business Days of
such decision. OPKO will ensure that the IDMC is provided with all information
and data that it requires as specified in the IDMC Charter, and Pfizer will
reasonably cooperate with OPKO in such regard. OPKO will ensure that all members
of the IDMC have any licenses, certifications and/or accreditations required by
Applicable Laws; and understand the Development Plan and their obligation to
comply therewith and all Applicable Laws in conducting such Trial(s). Any such
representations and warranties will be made for the benefit of OPKO and Pfizer
as third party beneficiaries. OPKO will ensure that each member completes the
Financial Disclosure Form. For clarity, if any of the foregoing individuals do
not complete such Financial Disclosure Form, such individuals may not
participate in the IDMC.
4.11. Environmental Health and Safety.
4.11.1. In conducting each Trial ***, OPKO will comply with all Applicable Laws,
including those relating to environmental, health and/or safety matters. For
clarity, OPKO will be solely responsible for establishing material and specimen
handling guidelines and for ensuring use of controls, including appropriate
personal protective equipment, that minimize potential worker exposure,
obtaining the material safety data sheets and providing the appropriate training
for workers who will potentially be exposed to any Compound, Device or Licensed
Product.
4.11.2. OPKO will promptly notify the JDC, in writing, of any worker claims of
suspected occupational illnesses related to working with any Compounds, Devices
or Licensed Products, or of any known facts or circumstances which could lead to
such claims, regardless of whether such claims are received during the Term or
any time thereafter. After termination of this Agreement for any reason, or
expiration of this Agreement, each Party will promptly notify the other Party of
any worker claims of suspected occupational illnesses related to working with
any Compounds, Devices or Licensed Products during the Term, of which it has
knowledge.
4.12 Trial Reports; Safety or Efficacy Data. With respect to each Trial ***,
OPKO shall provide Pfizer with access to all clinical data (in a format required
by Regulatory Authorities), the Trial Master File and a “topline” report, an
“interim study” report, if available, and a final complete study report, as well
as any other reports as required by the Development Plan. In the event that
there are any additional safety or efficacy data pertaining to any Trial ***
that come into the possession of OPKO after providing Pfizer with the final
complete study report, OPKO will prepare and promptly provide Pfizer with a
supplement to such report.
5. PAYMENTS.
5.1. Upfront Payment. The Parties hereby acknowledge that, within *** days of
the Original Effective Date, Pfizer made a one-time non-refundable and
non-creditable payment to OPKO of Two Hundred Eighty-Five Million U.S. Dollars
($285,000,000) (the “Upfront Payment”).
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5.2. Regulatory Milestone Payments. Pfizer shall pay to OPKO the amounts set
forth below within *** days following the first occurrence of each event
described below (each event, a “Regulatory Milestone” and each payment, a
“Regulatory Milestone Payment”), which amounts shall be non-refundable and
non-creditable against any other payments due under this Agreement.
Regulatory Milestone
Regulatory Milestone Payment
First achievement of *** of a Licensed Product for an Approved Indication in ***
***
First achievement of *** of a Licensed Product for an Approved Indication in ***
***
First achievement of *** of a Licensed Product for an Approved Indication ***
***
First achievement of *** of a Licensed Product for an Approved Indication in ***
***
First achievement of *** of a Licensed Product for an Approved Indication in ***
***
First achievement of *** of a Licensed Product for an Approved Indication ***
***
First achievement of *** of a Licensed Product for an Approved Indication in ***
***

For the avoidance of doubt: (a) each Regulatory Milestone Payment shall be
payable only once upon first achievement of the applicable Regulatory Milestone
and only on the first occurrence of the corresponding Regulatory Milestone,
regardless of the number of Licensed Products achieving such Regulatory
Milestone; (b) a Regulatory Milestone satisfied by a sublicensee or Affiliate of
OPKO shall be deemed to have been achieved by OPKO for the purposes of this
Section 5.2; and (c) to the extent any ***, which trigger a Regulatory
Milestone, Regulatory Milestone Payments shall be payable in respect of each
such *** as provided above. In addition, and for greater clarity, milestones
shall not be paid on ***.
5.3. Royalty Payments.
5.3.1. Royalties. Subject to the provisions of Section 5.5 ***, Pfizer shall pay
to OPKO royalties in the amount of the marginal rates set forth below of the
aggregate Net Sales resulting from the sales of all Licensed Products in the
Territory during each Pfizer Year of the applicable Royalty Term for each
Licensed Product (pro-rated for any partial Pfizer Year). Each marginal royalty
rate set forth in the table shall apply only to that portion of the Net Sales of
a given Licensed Product in the Territory during a given Pfizer Year that falls
within the indicated range.
Annual Worldwide Net Sales
Marginal Royalty Rate
Annual Worldwide Net Sales up to and including ***
***
Annual Worldwide Net Sales above ***, up to and including ***
***
Annual Worldwide Net Sales above ***
***

At such time as there is a commencement of the *** Profit Share ***, such that
royalties are no longer payable with respect to such *** pursuant to the
provisions of this Section 5.3.1, Pfizer’s payment obligations under this
Section 5.3.1 with respect to those *** which remain eligible for payment of
royalties shall then be calculated based upon
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the applicable table set forth below rather than the table set forth above for
purposes of this Section 5.3.1 (pro-rated for any partial Pfizer Year).

Royalties payable only for ***:
Annual Net Sales in the ***
Marginal Royalty Rate
Annual Net Sales in the *** up to and including ***
***
Annual Net Sales in the *** above ***, up to and including ***
***
Annual Net Sales in the *** above ***
***

Royalties payable only for ***:
Annual Net Sales in ***
Marginal Royalty Rate
Annual Net Sales in *** up to and including ***
***
Annual Net Sales in *** above ***, up to and including ***
***
Annual Net Sales in *** above ***
***

Royalties payable only for ***
Annual Net Sales in ***
Marginal Royalty Rate
Annual Net Sales in *** up to and including ***
***
Annual Net Sales in *** above ***, up to and including ***
***
Annual Net Sales in *** above ***
***

Royalties payable only for *** and ***:
Annual Net Sales in *** and ***
Marginal Royalty Rate
Annual Net Sales in *** and *** up to and including ***
***
Annual Net Sales in *** and *** above ***, up to and including ***
***
Annual Net Sales in *** and *** above ***
***

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Royalties payable only for *** and ***:
Annual Net Sales in *** and ***
Marginal Royalty Rate
Annual Net Sales in *** and *** up to and including ***
***
Annual Net Sales in *** and *** above ***, up to and including ***
***
Annual Net Sales in *** and *** above ***
***

Royalties payable only for *** and ***:
Annual Net Sales in *** and ***
Marginal Royalty Rate
Annual Net Sales in *** and *** up to and including ***
***
Annual Net Sales in *** and *** above ***, up to and including ***
***
Annual Net Sales in *** and *** above ***
***

5.3.2. ***. For each of the *** consecutive *** with respect to which royalties
are payable pursuant to Section 5.3, OPKO shall receive *** for such period for
all countries in the Territory:
Year
***
*** Period
***
*** Period
***
*** Period
***

At such time as there is a commencement of the *** Profit Share Term, such that
royalties are no longer payable with respect to such *** pursuant to the
provisions of this Section 5.3.2, Pfizer’s payment obligations under this
Section 5.3.2 shall be calculated based upon the applicable table set forth
below rather than the table set forth above for purposes of this Section 5.3.2.
For clarity, the tables set forth below are intended only to provide for
alternative *** amounts payable under this Section 5.3.2 for the *** months for
which *** are payable (as compared to the table set forth above), and shall not
be construed to require the payment of any additional amounts of royalty
payments beyond such *** month time period.

        *** payable only for ***:
Year
***
*** Period
***
*** Period
***
*** Period
***

        *** payable only for ***:
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Year
***
*** Period
***
*** Period
***
*** Period
***

        *** payable only for ***:
Year
***
*** Period
***
*** Period
***
*** Period
***

        *** payable only for *** and ***:
Year
***
*** Period
***
*** Period
***
*** Period
***

        
*** payable only for *** and ***:
Year
***
*** Period
***
*** Period
***
*** Period
***

        *** payable only for *** and ***:
Year
***
*** Period
***
*** Period
***
*** Period
***

5.4. Profit Share Payments.
5.4.1. Subject to the provisions of Section 5.5, Pfizer shall pay to OPKO gross
profit payments in the amount of the marginal rates set forth below of the
aggregate Franchise Gross Profit in *** with respect to Licensed Product and
Genotropin Product in *** during the *** Profit Share Term***, as applicable,
determined as set forth below, based on the percentage of annual Franchise Net
Sales attributable to Licensed Product in ***. Each marginal gross profit
payment rate set forth in the table shall apply only to that portion of the
Franchise Net Sales that falls within the indicated range. Franchise Gross
Profits for partial calendar years shall be determined by prorating the annual
aggregate
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thresholds for the relevant ***. An example calculation of gross profit payments
under this Section 5.4 is set forth in Schedule 5.4.
5.4.2. Subject to the caveat in the following sentence, in addition, if there is
a ***, which *** occurs not later than the *** anniversary of the commencement
of the Profit Share Term ***, then following the occurrence of such *** and
continuing until the ***, each threshold dollar amount set forth in the
left-hand-most column of the table set out below in this Section 5.4 applicable
to *** shall be reduced by an amount equal to *** which were realized in ***
during the *** period immediately preceding the occurrence of such ***.
Notwithstanding the foregoing, the reductions in threshold dollar amounts
contemplated by the prior sentence shall not be applicable in the event that
(i) Pfizer directly or indirectly *** with respect to, ***, including through
the effectuation of an *** agreement *** (ii) there is a subsequent ***, and
(iii) such *** period prior to the date of *** that were equal to at least ***
of the worldwide Net Sales of the *** for the same *** period. If, however,
(i) Pfizer directly or indirectly acquires, or obtains rights with respect to,
***, including through the effectuation of an *** agreement ***, (ii) there is a
subsequent ***, and (iii) such *** period prior to the date of *** that were
less than *** for the *** period, then following the occurrence of such *** and
continuing until the ***, each threshold dollar amount set forth in the
left-hand-most column of the table set out below in Section 5.4 applicable to
*** shall be ***.
*** Profit Share:
Annual Aggregate *** Franchise Net Sales
Less than or equal to *** of Annual Aggregate *** Franchise Gross Profit is
Attributable to Licensed Products
More than *** of Annual Aggregate *** Franchise Gross Profit is Attributable to
Licensed Products
Annual Aggregate *** Franchise Net Sales up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***, up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***, up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***
***
***

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 *** Profit Share:
Annual Aggregate *** Franchise Net Sales
Less than or equal to *** of Annual Aggregate *** Franchise Gross Profit is
Attributable to Licensed Products
More than *** of Annual Aggregate *** Franchise Gross Profit is Attributable to
Licensed Products
Annual Aggregate *** Franchise Net Sales up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***, up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***, up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***
***
***

*** Profit Share:
Annual Aggregate *** Franchise Net Sales
Less than or equal to *** of Annual Aggregate *** Franchise Gross Profit is
Attributable to Licensed Products
More than *** of Annual Aggregate *** Franchise Gross Profit is Attributable to
Licensed Products
Annual Aggregate *** Franchise Net Sales up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***, up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***, up to and including ***
***
***
Annual Aggregate *** Franchise Net Sales above ***
***
***

5.5. Royalty and Profit Share Payment Adjustments, Statements and Payments.
5.5.1. Adjustments. The following adjustments shall be made, on a Licensed
Product-by-Licensed Product and country-by-country basis, to the royalties
payable pursuant to Section 5.3 and the gross profit payments payable pursuant
to Section 5.4:
(a) No Adjustment for OPKO Third Party Agreements. Subject to Section 3.1.2,
OPKO shall be solely responsible for (i) all obligations (including any royalty
or other obligations that relate to the Licensed Technology) under its
agreements with Third Parties that are in effect as of the Original Effective
Date or that OPKO enters into during the Term, and (ii) all payments to
inventors (other than inventors that are Representatives of Pfizer) of the
Licensed Technology, including payments under inventorship compensation laws.
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(b) Third Party Patents. If Pfizer, in consultation with OPKO, reasonably (i)
determines it is necessary or reasonably useful to obtain a license from a Third
Party in order to Develop, Manufacture, Commercialize or use a Licensed Product
in a *** in the Territory and to pay a royalty or other consideration under such
license (including in connection with the settlement of a patent infringement
claim), or (ii) is or becomes subject to a final court or other binding order or
ruling requiring any payments, including the payment of a royalty to a Third
Party holder of Patent Rights in respect of sales of any Licensed Product in a
*** in the Territory, then, without limiting OPKO’s obligations under Section
10.3, the amount of Pfizer, its Affiliates or its sublicensee royalty payments
under Section 5.3 with respect to Net Sales for such Licensed Product in such
***, as well as gross profit payments under Section 5.4 with respect to
Franchise Gross Profits in such ***, shall each be reduced by *** of the amounts
payable and actually paid to Third Parties pursuant to any such Third Party
license or such order, such reduction to continue until all such amounts have
been expended, provided the reduction shall not exceed *** of the amounts
payable to OPKO in any Calendar Quarter.
5.5.2. Cumulative Royalties and Gross Profit Payments. The obligation to pay
royalties and/or gross profit payments under this Agreement shall be imposed
only once with respect to any sale of any Licensed Product.
5.5.3. Royalty and Gross Profit Payment Statements and Payments.
(a) Within *** days of the end of each Calendar Quarter, Pfizer shall deliver to
OPKO a report setting forth, for the most recent Pfizer Quarter ending during
such Calendar Quarter, the following information, on a Licensed
Product-by-Licensed Product, Genotropin Product-by-Genotropin Product,
country-by-country, and Territory-wide basis: (a) Net Sales of each Licensed
Product and Genotropin Product, (b) Franchise Gross Profits with respect to each
Licensed Product and Genotropin Product, (c) the basis for any adjustments to
the royalty or gross profit payment payable for the sale of any such Licensed
Product and Genotropin Product and (d) the royalty or gross profit payment due
hereunder for the sale of each such Licensed Product or Genotropin Product. No
such report shall be due for any Licensed Product or Genotropin Products (i)
before the First Commercial Sale of a Licensed Product in the *** or (ii) after
the Royalty Term and Profit Share Term for such Licensed Product has terminated
in *** in the Territory. The total royalty and gross profit payment due and
payable for the sale of all Licensed Products during a Pfizer Quarter shall be
paid within *** days following the end of such Calendar Quarter. Any adjustments
with respect to the calculation of any amount of royalties and/or gross profit
which were included in a previously submitted report delivered pursuant to this
Section 5.5.3(a) shall be reflected in the next such report delivered by Pfizer
to OPKO, such adjustments to be made in a manner consistent with the internal
accounting policies of Pfizer.
(b) *** shall be paid as follows: At the end of the *** period in respect of
which a *** is payable, Pfizer shall pay to OPKO within *** days after the end
of the *** period in question, and assuming the difference is a positive number,
the difference between (i) the applicable *** and (ii) the aggregate amount of
all the royalties due and payable to OPKO for the *** period actually paid to
OPKO in such period.
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5.6. ***. With respect to amounts due or otherwise payable to *** by *** in
connection with this Agreement, *** in connection with this Agreement.
5.7. Taxes and Payments.
5.7.1. Taxes and Withholding. It is understood and agreed between the Parties
that any payments made under this Agreement are exclusive of any value added or
similar tax (“VAT”), which shall be added thereon as applicable. Where VAT is
properly added to a payment made under this Agreement, the Party making the
payment will pay the amount of VAT only on receipt of a valid tax invoice issued
in accordance with the laws and regulations of the country in which the VAT is
chargeable. In addition, in the event any payments made by Pfizer pursuant to
this Agreement become subject to withholding taxes under the Applicable Laws or
regulations of any jurisdiction or Governmental Authority, Pfizer shall: (i)
deduct and withhold the amount of such taxes for the account of OPKO to the
extent required by Applicable Laws or regulations and such amounts payable to
OPKO shall be reduced by the amount of taxes deducted and withheld; (ii) pay the
amounts of such taxes to the proper Governmental Authority in a timely manner;
(iii) transmit to OPKO an official tax certificate or other evidence of such tax
obligations together with proof of payment from the relevant Governmental
Authority of all amounts deducted and withheld sufficient to enable OPKO, in
OPKO’s good faith opinion, to claim such payment of taxes; and (iv) cooperate
with OPKO in any way reasonably required to obtain available reductions, credits
and/or refund of such taxes. Any such withholding taxes required under
Applicable Laws or regulations to be paid or withheld shall be an expense of,
and borne solely by, OPKO. In order to assist Pfizer in its cooperation referred
to in clause (iv) of the foregoing sentence, OPKO shall provide Pfizer with a
valid Form W-8BEN-E, Certificate of Status of Beneficial Owner for United States
Tax Withholding and Reporting (Entities), certifying that OPKO is the beneficial
owner of the Payments within the meaning of the tax treaty in force between
Ireland and the United States (the “Treaty”).
5.7.2. Currency. All amounts payable and calculations under this Agreement shall
be in United States dollars. As applicable, Net Sales, Gross Profits and any
royalty or gross profit payment deductions shall be translated into United
States dollars at the exchange rate used by Pfizer, in the ordinary course, for
public financial accounting purposes. If, due to restrictions or prohibitions
imposed by national or international authority, a given payment cannot be made
as provided in this Section 5.7.2, the Parties shall consult with a view to
finding a prompt and acceptable solution. If the Parties are unable to identify
a mutually acceptable solution regarding such payment, then Pfizer may elect, in
its sole discretion, to deliver such payment in the relevant jurisdiction and in
the local currency of the relevant jurisdiction.
5.7.3. Method of Payment. Each payment hereunder shall be made by electronic
transfer in immediately available funds via either a bank wire transfer, an ACH
(automated clearing house) mechanism or any other means of electronic funds
transfer, at the Party to whom payment is due’s election, to the bank account as
set forth below or as designated by such Party in writing to the other Party at
least *** days before the payment is due:
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***
***
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5.8. Inspection of Records.
5.8.1. Record Keeping. Each Party shall keep and shall cause its Affiliates and
sublicensees to keep books and accounts of record setting forth gross sales of
the Licensed Product and Genotropin Products, Net Sales, expenses, and COGS on a
*** basis sufficient to enable the calculation of amounts payable hereunder to
be verified, as well as books and records of the costs and expenses associated
with Development activities. Each Party and its Affiliates and sublicensees
shall maintain such records during the Term and for a period of at least ***
after the final payment has been made under the Agreement.
5.8.2. Audits. Each Party, upon *** days’ prior notice from the other Party (the
“Auditing Party”), shall permit an independent certified public accounting firm
of nationally-recognized standing selected by the Auditing Party and reasonably
acceptable to the other Party (the “Audited Party”) to examine, at the Auditing
Party’s sole expense, the relevant books and records of the Audited Party and
its Affiliates as may be reasonably necessary to verify calculation of and the
amounts reported by the Audited Party in accordance with Section 5.5, the
payment of royalties and gross profit payments hereunder, and to confirm the
costs and expenses of each Party associated with Development activities. An
examination by either Party under this Section 5.8.2 shall not occur more than
*** in any calendar year and shall be limited to the pertinent books and records
for any calendar year ending not more than *** before the date of the request.
The accounting firm shall be provided access to such books and records at the
Audited Party’s or its Affiliates’ facility(ies) where such books and records
are normally kept and such examination shall be conducted during the Audited
Party’s normal business hours. The Audited Party may require the accounting firm
to sign a reasonably acceptable non-disclosure agreement before providing the
accounting firm with access to the Audited Party’s or its Affiliates’ facilities
or records. Upon completion of the audit, the accounting firm shall provide both
Pfizer and OPKO a written report disclosing any discrepancies in the reports
submitted the Audited Party and, in each case, specific details concerning any
discrepancies. No other information shall be provided to the Auditing Party.
5.8.3. Overpayments/Underpayments. If, after conducting an audit pursuant to
Section 5.8.2, the applicable accounting firm concludes that additional
royalties or gross profit payments were due to OPKO, then Pfizer will pay to
OPKO the additional royalties or gross profit payments within *** days of the
date Pfizer receives such accountant’s written report. Further, if the amount of
such underpayments exceeds more than *** of the amount that was properly payable
to OPKO, then Pfizer shall reimburse OPKO for
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OPKO’s out-of-pocket costs in connection with the audit. If the accounting firm
concludes that Pfizer overpaid royalties or gross profit payments to OPKO, then
OPKO shall refund such overpayments to Pfizer within *** days of the date OPKO
receives such accountant’s written report.
5.9. Confidentiality. Notwithstanding any provision of this Agreement to the
contrary, all reports and financial information of Pfizer, its Affiliates or its
sublicensees which are provided to or subject to review by OPKO under this
Section 5.9 shall be deemed to be Pfizer’s Confidential Information and subject
to the provisions of Article 7.
5.10. No Guarantee of Success. Pfizer and OPKO acknowledge and agree that
nothing in this Agreement will be construed as representing an estimate or
projection of (i) the successful Development or Commercialization of any
Licensed Product under this Agreement, (ii) the number of Licensed Products that
will or may be successfully Developed or Commercialized under this Agreement,
(iii) anticipated sales or the actual value of any Licensed Products that may be
successfully Developed or Commercialized under this Agreement or (iv) the
damages, if any, that may be payable if this Agreement is terminated for any
reason. Pfizer makes no representation, warranty or covenant, either express or
implied, that (A) it will successfully Commercialize or continue to
Commercialize any Licensed Product in any country, (B) if Commercialized, that
any Licensed Product will achieve any particular sales level, whether in any
individual country or cumulatively throughout the Territory, or (C) Pfizer will
devote, or cause to be devoted, any level of diligence or resources to
Developing or Commercializing any Licensed Product in any country, or in the
Territory in general, other than is expressly required under Article 3.
6. INTELLECTUAL PROPERTY.
6.1. Ownership and Inventorship.
6.1.1. Pre-Existing Intellectual Property. Subject to the licenses granted
pursuant to Article 2, and except for the Intellectual Property Rights assigned
to Pfizer pursuant to Section 6.2.2, each Party shall retain all right, title
and interest in and to any Intellectual Property Rights that are Controlled by
such Party prior to the Original Effective Date, or that are Controlled by such
Party on or after the Original Effective Date and are outside the scope of this
Agreement. For the avoidance of doubt, as between the Parties, OPKO shall retain
sole and exclusive ownership and all right, title and interest in and to all
Licensed OPKO Core Patents and the CTP Technology.
6.1.2. Developed Intellectual Property.
(a) As between the Parties, except for Licensed OPKO Core Patents, Pfizer shall
own all right, title and interest in and to any Intellectual Property Rights
conceived by Pfizer or its Affiliates, subcontractors or sublicensees in the
course of conducting Pfizer’s activities and rights under this Agreement, and
that do not name any inventors having an obligation of assignment to OPKO at the
time such intellectual property is conceived, discovered, developed or otherwise
made (collectively herein, “Pfizer Developed IP”).
(b) As between the Parties, OPKO shall own and retain all right, title and
interest in and to any Intellectual Property Rights conceived, developed or
otherwise first made or reduced to practice by OPKO or its Affiliates,
subcontractors or sublicensees in the course of conducting OPKO’s activities and
rights under this Agreement, and that do not name any inventors having an
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obligation of assignment to Pfizer at the time such intellectual property is
conceived, discovered, developed or otherwise made (collectively herein, “OPKO
Developed IP”).
(c) Except for the Licensed OPKO Core Patents, the Parties shall jointly own all
Intellectual Property Rights conceived, developed or otherwise first made or
reduced to practice during the course of the Development, Manufacturing or
Commercialization of the Compound or Licensed Products hereunder, and that name
any inventors having an obligation of assignment to Pfizer and any inventors
having an obligation of assignment to OPKO at the time such intellectual
property is conceived, discovered, developed or otherwise made (collectively
herein, “Joint Developed IP”).
(d) For the avoidance of doubt, OPKO Developed IP and OPKO’s rights in and to
any Joint Developed IP shall be deemed and treated as Licensed Technology
licensed by OPKO under Section 2.1 of this Agreement to the extent such OPKO
Developed IP and Joint Developed IP relate to Licensed Product.
(e) For purposes of this Section 6.1.2, inventorship shall be determined in
accordance with applicable United States intellectual property laws, regardless
of the country in which such intellectual property is conceived, discovered,
developed or otherwise made.
(f) With regard to intellectual property conceived, discovered, developed or
otherwise made or reduced to practice during the course of the Development,
Manufacturing or Commercialization of the Compound or Licensed Products, each
Party shall promptly notify the other Party of any such intellectual property of
which it becomes aware, and the Parties shall confer in a timely manner in order
to take such actions as may be reasonably necessary to protect such intellectual
property, including but not limited to filing for patent protection.
6.2. Trademarks.
6.2.1. All Trademarks filed in the Territory shall be owned by Pfizer, and
applications for registration of such Trademarks shall be filed and prosecuted
by Pfizer with reasonable assistance from OPKO, if necessary. All costs of the
filing of applications for registration of Trademarks in the Territory shall be
borne solely by Pfizer.
6.2.2. Effective as of the Original Effective Date, OPKO hereby transfers,
releases and assigns to Pfizer, all right, title and interest in and to the
Trademark LAGOVA and any associated trademarks, logos, copyrights and domain
names related thereto, together with (1) the goodwill associated therewith, and
(2) all common law rights in the marks and associated Intellectual Property
Rights, for its own use and behalf and for the use and behalf of its successors,
assigns, licensees and other legal representatives.
6.3. Patent Prosecution and Maintenance.
6.3.1. Prosecution and Maintenance of Licensed OPKO Core Patents and OPKO
Developed IP.
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(a) First Right to File, Prosecute and Maintain. Subject to Pfizer’s rights set
forth in Section 6.3.1(b) below, OPKO shall have the first right, but not the
obligation, to file, prosecute and maintain the Licensed OPKO Core Patents and
the OPKO Developed IP (together, “OPKO Prosecuted IP”) throughout the world,
using outside patent counsel, patent agents and an annuity service of OPKO’s
choice that are reasonably acceptable to Pfizer. For avoidance of doubt, nothing
herein shall be construed to give OPKO the right to use Pfizer’s Confidential
Information in prosecuting OPKO Prosecuted IP or in connection with such
prosecution, or prosecute Licensed hGH-Specific Patents (except as otherwise
provided with respect to certain continuations, continuations-in part and
divisionals pursuant to Section 6.3.2(d)), without Pfizer’s prior written
consent. At least forty-five (45) calendar days prior to the applicable date for
national stage filing of any international patent application filed under the
Patent Cooperation Treaty that is a OPKO Prosecuted IP, OPKO shall provide
Pfizer with a list of countries and regions into which OPKO intends to file such
national stage applications. This list shall include at least the Major Market
Countries. Pfizer may request that OPKO file such national stage applications in
one or more additional countries. Except as provided in Section 6.3.1(b), OPKO
shall retain the sole right and responsibility for prosecuting, maintaining and
defending the OPKO Prosecuted IP filed under this Section 6.3.1. OPKO shall be
responsible for *** and Pfizer shall be responsible for *** of direct
out-of-pocket costs incurred in such activities; provided, however, that if
Pfizer provides a written request to OPKO that OPKO file the OPKO Prosecuted IP
in a jurisdiction outside the Major Market Countries, *** shall be responsible
for *** of direct out-of-pocket costs (including any required translation costs)
incurred in such activities.
(b) Review and Comment. OPKO shall keep Pfizer advised on the status of the
prosecution and maintenance of all Licensed Products and Compounds of the OPKO
Prosecuted IP in the ordinary course of patent prosecution and in such manner as
OPKO or OPKO’s counsel and/or management is informed. OPKO shall provide
quarterly docket reports as well as updated docket reports as requested by
Pfizer for all Licensed Product and Compounds of the OPKO Prosecuted IP. For the
Major Market Countries, and any other countries or patent offices specifically
requested in writing by Pfizer, OPKO shall allow Pfizer a reasonable opportunity
and reasonable time to review and comment regarding substantive communications
from the relevant patent offices or Governmental Authorities and drafts of any
responses or other proposed substantive filings before any such filings are
submitted to any relevant patent offices or Governmental Authorities, and OPKO
shall consider in good faith any reasonable comments offered by Pfizer in
preparing any final filings to be submitted to any relevant patent offices or
Governmental Authorities.
(c) OPKO Election to Not Prosecute or Maintain. If OPKO at any time abandons or
declines to continue prosecution or maintenance of the patents and applications
in a particular country for any Licensed Product and Compounds of the OPKO
Prosecuted IP, OPKO shall provide Pfizer with forty-five (45) days prior written
notice to such effect, and OPKO shall have no responsibility with respect to the
prosecution or maintenance of the applicable Patent Right and no responsibility
for any expenses incurred in connection with such Patent Right after the end of
such forty-five (45) day period. If Pfizer gives written notice to OPKO before
the end of such forty-five (45) day period that Pfizer elects to
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continue prosecution or maintenance, (a) OPKO, upon Pfizer’s request, shall make
reasonable efforts to timely execute such documents and perform such acts, at
Pfizer’s expense, as may be reasonably necessary to permit Pfizer to prosecute
and maintain such Patent Right at its sole expense, (b) Pfizer shall keep OPKO
advised on the status of the prosecution and maintenance of all such Patent
Rights annually and at other times as reasonably requested by OPKO, and (c) it
is agreed that Pfizer may use internal patent counsel, filing clerks and
paralegals employed by Pfizer for such activities, including for coordination of
worldwide filings of such Patent Rights, for prosecution before the European
Patent Office, and for direction of instructing U.S. outside counsel and ex-U.S.
patent agents, including providing draft applications and responses, and that
Pfizer may employ its preferred patent agents and/or members of the “Pfizer
Legal Alliance” to conduct such activities as required for U.S. and ex-U.S.
prosecution. If Pfizer does not give written notice to OPKO before the end of
such forty-five (45) day period that Pfizer elects to continue prosecution or
maintenance of such Patent Right, OPKO shall be entitled to allow such Patent
Right to lapse. For avoidance of doubt, nothing herein shall be construed to
give Pfizer the right to use OPKO’s Confidential Information in prosecuting OPKO
Prosecuted IP or in connection with such prosecution without OPKO’s prior
written consent.
(d) Patent Term Restoration and Extension. Subject to Pfizer’s rights as
provided in Section 6.3.2(e), OPKO shall have the exclusive right, but not the
obligation, to seek patent term extensions, supplemental protection certificates
and the like available under Applicable Law, including 35 U.S.C. § 156 and
applicable foreign counterparts, in any country in the Territory in relation to
Licensed Product and Compounds of the OPKO Prosecuted IP. OPKO and Pfizer will
cooperate in connection with all such activities. OPKO will give due
consideration to all suggestions and comments of Pfizer regarding any such
activities, but in the event of a disagreement between the Parties, OPKO will
have the final decision-making authority; provided, however, that OPKO will seek
(or will allow Pfizer to seek) to extend, including through the use of
supplemental protection certificates and the like, any OPKO Prosecuted IP at
Pfizer’s request unless, in OPKO’s reasonable legal determination, such OPKO
Prosecuted IP may not be extended under Applicable Law without limiting OPKO’s
right to extend any other Patent Right.
(e) European Patents with Unitary Effect and Jurisdiction of European Unified
Patent Court. OPKO shall have the exclusive right, but not the obligation, to
determine in relation to the OPKO Prosecuted IP whether any Patent Right sought
in Europe shall be obtained as a national patent of a European state, or as a
European patent with unitary effect, including whether to validate a European
patent as a national patent or a patent with unitary effect. Where OPKO has the
first or sole right to enforce any Patent Right under this Agreement, unless
such right to enforce has passed to Pfizer, OPKO shall have the sole right, at
any relevant time in the prosecution or enforcement of such Patent Right, to
determine whether to subject such Patent Right to the jurisdiction of the
Unified Patent Court, including with respect to any infringement or nullity
action, and with respect to any decision whether to opt-in or opt-out of such
jurisdiction. OPKO and Pfizer shall cooperate in connection with all such
activities, taking such action in Pfizer’s name if so required. OPKO, its agents
and attorneys will give due consideration to all suggestions and comments of
Pfizer regarding such
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determinations, but in the event of a disagreement between the Parties, OPKO
shall have the final decision-making authority.
(f) For the avoidance of doubt, OPKO shall have no obligations to Pfizer with
regard to the prosecution and maintenance of OPKO Prosecuted IP as provided in
Subsections 6.3.1(a)-(e), and Pfizer shall have no rights with regard to the
prosecution and maintenance of OPKO Prosecuted IP as provided in Subsections
6.3.1(a)-(e), to the extent such OPKO Prosecuted IP does not claim or otherwise
impact Intellectual Property Rights associated with the Compounds and/or the
Licensed Products.
6.3.2. Prosecution and Maintenance of Licensed hGH-Specific Patents and Pfizer
Developed IP.
(a) First Right to File, Prosecute and Maintain. Subject to OPKO’s rights set
forth in Section 6.3.2(c) below, Pfizer shall have the first right, but not the
obligation, to file, prosecute and maintain the Licensed hGH-Specific Patents
and Pfizer Developed IP (together, “Pfizer Prosecuted IP”) throughout the world,
using outside patent counsel, patent agents and an annuity service of Pfizer’s
choice that are reasonably acceptable to OPKO. It is agreed that Pfizer may use
internal patent counsel, filing clerks and paralegals employed by Pfizer for
such activities, including for coordinating worldwide filings of such Patent
Rights, for prosecution before the European Patent Office, and for directly
instructing U.S. outside counsel and ex-U.S. patent agents, including providing
draft applications and responses. It is also agreed that Pfizer may employ its
preferred patent agents and/or members of the “Pfizer Legal Alliance” to conduct
such activities as required for U.S. and ex-U.S. prosecution. For avoidance of
doubt, nothing herein shall be construed to give Pfizer the right to use OPKO’s
Confidential Information or prosecute Licensed OPKO Core Patents in prosecuting
Pfizer Prosecuted IP or in connection with such prosecution without OPKO’s prior
written consent. At least forty-five (45) calendar days prior to the applicable
date for national stage filing of any international patent application filed
under the Patent Cooperation Treaty that is a Licensed hGH-Specific Patents or
Pfizer Developed IP, Pfizer shall provide OPKO with a list of countries and
regions in which Pfizer intends to file such national stage applications. This
list shall include at least the Major Market Countries. OPKO may request that
Pfizer file such national stage applications in one or more additional
countries. Except as provided in Section 6.3.1(c), Pfizer shall retain the sole
right and responsibility for prosecuting, maintaining and defending the Pfizer
Prosecuted IP filed under this Section 6.3.2(a). *** shall be responsible for
*** of direct out-of-pocket costs incurred in such activities.
(b) Review and Comment. Pfizer shall keep OPKO advised on the status of the
prosecution and maintenance of all Pfizer Prosecuted IP in the ordinary course
of patent prosecution and in such manner as Pfizer or Pfizer counsel and/or
management is informed. Pfizer shall provide quarterly docket reports as well as
updated docket reports as requested by OPKO. For the Major Market Countries, and
any other countries or patent offices specifically requested in writing by OPKO,
Pfizer shall allow OPKO a reasonable opportunity and reasonable time to review
and comment regarding substantive communications from the relevant patent
offices or Governmental Authorities and drafts of any responses or other
proposed substantive filings before any such filings are
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submitted to any relevant patent offices or Governmental Authorities, and Pfizer
shall consider in good faith any reasonable comments offered by OPKO in
preparing any final filings to be submitted to any relevant patent offices or
Governmental Authorities.
(c) Pfizer Election to Not Prosecute or Maintain. If Pfizer makes a decision to
abandon or declines to continue prosecution or maintenance of the patents and
applications in a particular country for any Pfizer Prosecuted IP, Pfizer shall
provide OPKO with forty-five (45) days prior written notice to such effect, and
Pfizer shall have no responsibility with respect to the prosecution or
maintenance of the applicable Patent Right and no responsibility for any
expenses incurred in connection with such Patent Right after the end of such
forty-five (45) day period. If OPKO gives written notice to Pfizer before the
end of such forty-five (45) day period that OPKO elects to continue prosecution
or maintenance, (a) Pfizer, upon OPKO’s request, shall make reasonable efforts
to timely execute such documents and perform such acts, at OPKO’s expense, as
may be reasonably necessary to permit OPKO to prosecute and maintain such Patent
Right at its sole expense and (b) OPKO shall keep Pfizer advised on the status
of the prosecution and maintenance of all such Patent Rights annually and at
other times as reasonably requested by Pfizer. If OPKO does not give written
notice to Pfizer before the end of such forty-five (45) day period that OPKO
elects to continue prosecution or maintenance of such Patent Right, Pfizer shall
be entitled to allow such Patent Right to lapse. For avoidance of doubt, nothing
herein shall be construed to give OPKO the right to use Pfizer’s Confidential
Information in prosecuting Pfizer Prosecuted IP or in connection with such
prosecution without Pfizer’s prior written consent.
(d) Certain Continuations or Divisionals of Licensed hGH-Specific Patents Filed
by OPKO. If OPKO believes that there is subject matter in a Licensed
hGH-Specific Patent which can form the basis of a patent application which would
be considered a Licensed OPKO Core Patent or a Patent Right unrelated to the
Compound or Licensed Product, and OPKO wishes to file a continuation,
continuation-in-part or divisional application relating to such subject matter,
OPKO shall communicate this to Pfizer and provide a copy of such application to
Pfizer prior to the filing of this application, and after the application has
been filed all official correspondence and draft responses thereto at least ten
(10) Business Days before such responses are intended to be filed. Pfizer shall
have the opportunity to comment on this application and the draft responses, and
such comments shall be reasonably considered and addressed by OPKO. After
communication with and review by Pfizer, OPKO shall have the sole right, but not
the obligation to prosecute such applications throughout the world claiming
priority to, or the benefit, of a Licensed hGH-Specific Patent as outlined
above, provided that the claims are not directed toward the Compound or any
Licensed Product.
(e) Patent Term Restoration and Extension. Upon any Regulatory Approval, Pfizer
shall have the exclusive right, but not the obligation, to seek, in OPKO’s name
if so required, patent term extensions, supplemental protection certificates and
the like available under Applicable Law, including 35 U.S.C. § 156 and
applicable foreign counterparts, in any country in the Territory in relation to
the Pfizer Prosecuted IP. OPKO shall have no right to seek patent term
extensions, supplemental protection certificates and the like as provided in
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Section 6.3.1(d) unless (i) Pfizer, in its reasonable discretion, determines not
to seek such patent term extensions, supplemental protection certificates and
the like in relation to the Pfizer Prosecuted IP, or (ii) the applicable time
period to seek such patent term extensions, supplemental protection certificates
and the like in relation to the Pfizer Prosecuted IP has lapsed or expired.
Pfizer and OPKO will cooperate in connection with all such activities. Pfizer
will give due consideration to all suggestions and comments of OPKO regarding
any such activities, but in the event of a disagreement between the Parties,
Pfizer will have the final decision-making authority; provided, however, that
Pfizer will seek (or will allow OPKO to seek) to extend, including through the
use of supplemental protection certificates and the like, any Pfizer Prosecuted
IP at OPKO’s request unless in Pfizer’s reasonable legal determination such
Pfizer Prosecuted IP may not be extended under Applicable Law without limiting
Pfizer’s right to extend any other Patent Right.
(f) European Patents with Unitary Effect and Jurisdiction of European Unified
Patent Court. Pfizer shall have the exclusive right, but not the obligation, to
determine in relation to the Pfizer Prosecuted IP whether any Patent Right
sought in Europe shall be obtained as a national patent of a European state, or
as a European patent with unitary effect, including whether to validate a
European patent as a national patent or a patent with unitary effect. Where
Pfizer has the first or sole right to enforce any Patent Right under this
Agreement, unless such right to enforce has passed to OPKO, Pfizer shall have
the sole right, at any relevant time in the prosecution or enforcement of such
Patent Right, to determine whether to subject such Patent Right to the
jurisdiction of the Unified Patent Court, including with respect to any
infringement or nullity action, and with respect to any decision whether to
opt-in or opt-out of such jurisdiction. Pfizer and OPKO shall cooperate in
connection with all such activities, taking such action in OPKO’s name if so
required. Pfizer, its agents and attorneys will give due consideration to all
suggestions and comments of OPKO regarding such determinations, but in the event
of a disagreement between the Parties, Pfizer shall have the final
decision-making authority.
6.3.3. Liability. To the extent that a Party is obtaining, prosecuting or
maintaining a Patent Right or otherwise exercising its rights under this Section
6.3.3, neither such Party, nor any of its Affiliates, employees, agents or
representatives, shall be liable to the other Party in respect of any act,
omission, default or neglect on the part of any such Affiliate, employee, agent
or representative in connection with such activities undertaken in good faith.
6.3.4. Cooperation. Each Party shall provide the other Party with all reasonable
assistance and cooperation in the patent prosecution and extension efforts in
accordance with this Section 6.3.4, including by providing any necessary powers
of attorney and executing any other required documents or instruments for such
prosecution or extension applications.
6.3.5. Status Updates. Each Party shall provide the other Party with a written
status update on the Licensed Patent Rights, including any updates to the list
in Schedule 1.98, at least once every ***, or earlier upon the reasonable
request of the other Party.
6.4. Enforcement and Defense of Patent Rights.
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6.4.1. Notification. Each Party will promptly notify the other Party in writing
of any actual, potential, suspected or threatened infringement, misappropriation
or other violation by a Third Party of any Licensed Patent Right of which it
becomes aware (“Third Party Infringement”).
6.4.2. Control.
(a) Except as otherwise provided in this Section 6.4.2(a), Pfizer will have the
sole right, but not the obligation, to institute litigation or take other steps
to remedy Third Party Infringement of any Licensed Patent Rights other than
Licensed OPKO Core Patents, and any such litigation or steps will be at Pfizer’s
expense; provided that any recoveries resulting from such litigation or steps
relating to Third Party Infringement, after deducting Pfizer’s out of pocket
expenses (including counsel fees and expenses) in pursuing such claim, will be
deemed Net Sales of Licensed Products during the Royalty Term and Franchise
Gross Profit during the Profit Share Term. Pfizer will not, without the prior
written consent of OPKO, enter into any compromise or settlement relating to
such litigation that (i) admits the invalidity or unenforceability of any
Licensed Patent Right or Pfizer Developed CTP IP, (ii) requires Pfizer to
abandon any Licensed Patent Right or Pfizer Developed CTP IP, or (iii) amends
the claim. In order to establish standing, OPKO, upon request of Pfizer, agrees
to timely commence or to join in any such litigation, at Pfizer’s expense, and
in any event to cooperate with Pfizer in such litigation or steps at Pfizer’s
expense. OPKO will have the right to consult with Pfizer about such litigation
and to participate in and be represented by independent counsel in such
litigation at OPKO’s expense. Pfizer will keep OPKO reasonably apprised of the
status of such litigation and shall provide to OPKO all relevant communications,
notices and/or documents in a timely fashion.
(b) Except as otherwise provided in this Section 6.4.2(b), OPKO shall have the
first right, but not the obligation, to institute litigation or take other steps
to remedy Third Party Infringement of any Licensed OPKO Core Patents and any
such litigation or steps will be at OPKO's expense. OPKO will keep Pfizer
adequately informed, consult with and work closely with Pfizer, and reasonably
consider all recommendations of Pfizer, regarding any such litigation. OPKO will
not, without the prior written consent of Pfizer enter into any compromise or
settlement relating to such litigation that (i) admits the invalidity or
unenforceability of any Licensed Patent Right or Pfizer Developed CTP IP, (ii)
requires Pfizer to abandon any Licensed Patent Right or Pfizer Developed CTP IP,
or (iii) amends the claim. In order to establish standing, Pfizer, upon request
of OPKO, agrees to timely commence or to join in any such litigation, at OPKO's
expense, and in any event to cooperate with OPKO in such litigation or steps at
OPKO's expense. As noted above, Pfizer shall consult with OPKO regarding such
litigation and have the right to participate in and be represented by
independent counsel in such litigation at Pfizer's expense. OPKO will keep
Pfizer fully apprised of the status of the litigation and shall provide to
Pfizer all relevant communications, notices and/or documents, and proposed
filings, in a timely fashion. If OPKO decides not to institute litigation or
take other steps to remedy Third Party Infringement of any Licensed OPKO Core
Patent Right (relating to the Compound or Licensed Product), or if OPKO fails to
institute litigation or otherwise take steps to remedy Third Party Infringement
within thirty (30) days of its receipt of notice of infringement or such earlier
time as required to meet a
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deadline in the relevant jurisdiction for instituting such litigation, then
Pfizer has the second right, but not the obligation to institute such litigation
or take other steps to remedy such Third Party infringement at Pfizer's expense.
OPKO will have the right to consult with Pfizer about such litigation and to
participate in and be represented by independent counsel in such litigation at
OPKO’s expense. Pfizer will keep OPKO reasonably apprised of the status of such
litigation and shall provide to OPKO all relevant communications, notices and/or
documents in a timely fashion.
6.4.3. Pfizer Election to Not Enforce or Defend. If Pfizer fails to institute
litigation or otherwise take steps to remedy Third Party Infringement within ***
days of its receipt of notice, then OPKO will have the right, but not the
obligation, upon *** prior notice to Pfizer, at OPKO’s expense, to institute any
such litigation; provided, however, that OPKO will only have the foregoing right
if Pfizer would not be required (by Applicable Law or otherwise) to join such
litigation as a party and such litigation would not involve a Patent Right
covering a then-existing Licensed Product. Pfizer will have no obligation to
cooperate with OPKO in any such litigation. Neither Party will incur any
liability to the other Party as a consequence of any litigation initiated or
pursued pursuant to this Section 6.4.3 or any unfavorable decision resulting
therefrom, including any decision holding any Licensed Patent Right invalid or
unenforceable.
6.4.4. Other Actions by Third Parties. Each Party will promptly notify the other
Party in the event of any legal or administrative action by any Third Party
involving any Licensed Patent Right or Pfizer Developed CTP IP of which it
becomes aware, including any nullity, opposition, revocation, interference,
reexamination or compulsory licensing proceeding. Pfizer will have the first
right, but not the obligation, to defend against any such action involving any
Licensed Patent Right, in its own name (to the extent permitted by Applicable
Law) or OPKO’s name, and any such defense will be at Pfizer’s expense. OPKO, at
Pfizer’s request, agrees to join in any such action at Pfizer’s expense and in
any event to cooperate with Pfizer at Pfizer’s expense. If Pfizer fails to
defend against any such action involving a Licensed Patent Right, then OPKO will
have the right to defend such action, in its own name, and any such defense will
be at OPKO’s expense. Pfizer shall keep OPKO reasonably apprised of the status
of such Actions and shall allow OPKO a reasonable opportunity and reasonable
time to review and comment regarding substantive communications and shall give
due consideration to any reasonable comments offered by OPKO.
6.5. Allegations of Infringement; Third Party Licenses.
6.5.1. Notification. If the Development, Manufacture, Commercialization or use
of any Compound or Licensed Product, the practice of any Licensed Technology, or
the exercise of any other right granted by OPKO to Pfizer hereunder
(collectively, the “Licensed Activities”) by Pfizer or any of its Affiliates or
permitted sublicensees or the practice of any Licensed Technology by OPKO is
alleged by a Third Party to infringe, misappropriate or otherwise violate such
Third Party’s Patent Rights or other Intellectual Property Rights, OPKO will
notify Pfizer in writing promptly upon becoming aware of such allegation.
Additionally, if OPKO determines that, based upon the review of any Third Party
Patent Right or other Third Party Intellectual Property Rights, it may be
desirable to obtain a license from such Third Party with respect thereto so as
to avoid any potential claim of infringement by such Third Party against either
Party or their respective Affiliates or sublicensees, then OPKO will promptly
notify Pfizer of such determination.
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6.5.2. Pfizer Option to Negotiate. If Pfizer determines, in its reasonable
discretion, that, in order for Pfizer, its Affiliates or permitted sublicensees
to engage in the Licensed Activities, it is necessary to obtain a license under
one or more Patent Rights or other Intellectual Property Rights Controlled by a
Third Party, then Pfizer will have the right, but not the obligation, to
negotiate and enter into a license or other agreement with such Third Party. All
amounts payable under any such license or agreement with a Third Party will
reduce Pfizer’s royalty and gross profit payment obligations under this
Agreement as and to the extent provided in Section 5.5.1(b). Pfizer shall
provide OPKO with a copy of all such Patent Rights, shall keep OPKO reasonably
apprised of the status of such negotiations, and shall provide to OPKO copies of
all relevant communications and/or documents in a timely fashion.
6.6. Third Party Infringement Suits.
6.6.1. Notification. Each Party will promptly notify the other Party in the
event that any Third Party files suit or brings any other action alleging patent
infringement by Pfizer or OPKO or any of their respective Affiliates or
sublicensees with respect to the Development, Manufacture, Commercialization or
use of any Compound or Licensed Product or the practice of Licensed Technology
(any such suit or other action referred to herein as an “Infringement Claim”).
6.6.2. Control. In the case of any Infringement Claim against Pfizer (including
its Affiliates or sublicensees) alone or against both Pfizer and OPKO (including
its Affiliates), Pfizer will have the right, but not the obligation, to control
the defense of such Infringement Claim, including control over any related
litigation, settlement, appeal or other disposition arising in connection
therewith. OPKO will cooperate with Pfizer and will have the right to consult
with Pfizer concerning any Infringement Claim and to participate in and be
represented by independent counsel in any associated litigation in which OPKO is
a party at OPKO’s own expense. If Pfizer elects to control the defense of any
Infringement Claim then Pfizer will continue to have the right to control using
counsel of its own choice and will bear *** of its own attorneys’ fees incurred
in investigating, preparing or defending such Infringement Claim. In the case of
any Infringement Claim against OPKO alone, Pfizer will have the right to consult
with OPKO concerning such Infringement Claim, and Pfizer, upon request of OPKO,
will reasonably cooperate with OPKO at OPKO’s expense (but Pfizer will have no
obligation to join any Infringement Claim or associated litigation).
6.7. Orange Book Information. Pfizer will have the sole right, but not the
obligation, to submit to all applicable Governmental Authorities patent
information pertaining to each Licensed Product pursuant to 21 U.S.C. §
355(b)(1)(G) (or any amendment or successor statute thereto), any similar
statutory or regulatory requirement enacted in the future regarding biologic
products, or any similar statutory or regulatory requirement in any non-U.S.
country or other regulatory jurisdiction. Pfizer shall keep OPKO reasonably
apprised of the status of such submissions and shall provide to OPKO all
relevant communications, notices and/or documents regarding such submissions in
a timely fashion.
6.8. Biosimilar Notices. Notwithstanding any provision of this Agreement to the
contrary, each Party shall, within three (3) Business Days after receipt
thereof, give written notice to the other of any notice received from a Third
Party of an application for FDA approval under the Biologics Price Competition
and Innovation Act of 2009 (or any amendment or successor statute thereto) of a
Biosimilar Product, or any certification under a similar statutory or regulatory
requirement in any non-United States country in the Territory, claiming that a
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Licensed Patent Right covering any Product is invalid or that infringement will
not arise from the Development, Manufacture or Commercialization of a proposed
Biosimilar Product by a Third Party. Upon the giving of such notice, Pfizer
shall have the first right but not the obligation, to bring an infringement
action against such Third Party in connection with such certification, with the
rights and obligations of the Parties as set forth in Section 6.6. Pfizer shall
notify OPKO at least ten (10) Business Days prior to the date set forth by
statute or regulation with respect to the first response to be made by the BLA
holder, of its intent to exercise, or not exercise, this right, and, if Pfizer
does not exercise this right, the Parties will have the rights and obligations
as set forth in Section 6.6. Any infringement action against a Third Party
arising under this Section 6.8 shall be governed by the provisions of this
Section 6.8.
7. CONFIDENTIALITY.
7.1. Definition. “Confidential Information” means, with respect to each Party,
all Licensed Know-How or other information, including proprietary information
and materials (whether or not patentable) regarding or embodying such Party’s
technology, products, business information or objectives, that is communicated
by or on behalf of the Disclosing Party to the Receiving Party or its permitted
recipients, on or after the Original Effective Date, but only to the extent that
such Licensed Know-How or other information in written form is marked in writing
as “confidential” at the time of disclosure, and such Licensed Know-How or other
information disclosed orally or in non-tangible form is (a) identified by the
Disclosing Party as “confidential” at the time of disclosure and (b) within
thirty (30) days thereafter, the Disclosing Party provides a written summary of
such Know-How or other information marked as “confidential”. Notwithstanding the
foregoing, information disclosed orally or in non-tangible form that is not
subsequently summarized in writing shall be treated as Confidential Information
if the circumstances of the disclosure or the nature of the information would
reasonably be expected to be confidential. Confidential Information does not
include any Licensed Know-How or other information that (a) was already known by
the Receiving Party (other than under an obligation of confidentiality to the
Disclosing Party) at the time of disclosure by or on behalf of the Disclosing
Party, (b) was generally available to the public or otherwise part of the public
domain at the time of its disclosure to the Receiving Party, (c) became
generally available to the public or otherwise part of the public domain after
its disclosure to the Receiving Party, other than through any act or omission of
the Receiving Party in breach of its obligations under this Agreement, (d) was
disclosed to the Receiving Party, other than under an obligation of
confidentiality, by a Third Party who had no obligation to the Disclosing Party
not to disclose such information to the Receiving Party or (e) was independently
discovered or developed by or on behalf of the Receiving Party without the use
of any Confidential Information belonging to the Disclosing Party. The terms and
conditions of this Agreement will be considered Confidential Information of both
Parties.
7.2. Obligation; Term. Except to the extent otherwise expressly authorized by
this Agreement, the Parties agree that, during the Term and for *** thereafter,
each Party (the “Receiving Party”) receiving any Confidential Information of the
other Party (the “Disclosing Party”) hereunder will: (a) keep the Disclosing
Party’s Confidential Information confidential; (b) not disclose, or permit the
disclosure of, the Disclosing Party’s Confidential Information; and (c) not use,
or permit to be used, the Disclosing Party’s Confidential Information for any
purpose other than as expressly permitted under the terms of this Agreement. For
clarity, use of the Disclosing Party’s Confidential Information for the purpose
of invalidating Licensed Patent Rights is not a purpose expressly permitted
under the terms of the Agreement.
7.3. Disclosure to Party Representatives. Notwithstanding the provisions of
Section 7.2, the Receiving Party may disclose Confidential Information belonging
to the Disclosing Party
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to the Receiving Party’s Representatives who (a) have a need to know such
Confidential Information in connection with the performance of the Receiving
Party’s obligations or the exercise of the Receiving Party’s rights under this
Agreement and (b) have agreed in writing to non-disclosure and non-use
provisions with respect to such Confidential Information that are at least as
restrictive as those set forth in this Article 7.
7.4. Disclosure to Third Parties. Notwithstanding the provisions of Section 7.2,
each Party may disclose Confidential Information belonging to the other Party to
the extent such disclosure is reasonably necessary:
7.4.1. to Governmental Authorities (a) to the extent desirable to obtain or
maintain Regulatory Approvals for any Compound or Licensed Product within the
Territory, and (b) in order to respond to inquiries, requests or investigations
relating to any Compound, Licensed Product or this Agreement;
7.4.2. to outside consultants, contractors, advisory boards, managed care
organizations, non-clinical and clinical investigators, and bona fide potential
or actual sublicensees, collaborators, partners or permitted assignees, in each
case to the extent desirable to Develop, register or Commercialize any Compound
or Licensed Product; provided that the Receiving Party will obtain the same
confidentiality obligations from such Third Parties as it obtains with respect
to its own similar types of confidential information;
7.4.3. in connection with filing or prosecuting Patent Rights or Trademarks as
permitted by this Agreement;
7.4.4. in connection with prosecuting or defending litigation as permitted by
this Agreement;
7.4.5. in connection with posting results of and other information about
clinical trials to clinicaltrials.gov or PhRMA websites; or
7.4.6. to the extent necessary or desirable in order to enforce its rights under
this Agreement.
If a Party deems it reasonably necessary to disclose Confidential Information
belonging to the other Party pursuant to this Section 7.4, then the disclosing
Party shall to the extent possible give sufficient advance written notice of
such disclosure to the other Party and take such measures to ensure confidential
treatment of such information as is reasonably required by the other Party, at
the other Party’s expense. If reasonably practicable under the circumstances,
the disclosing party shall give the other Party sufficient advance notice of the
text that such Party will have the opportunity to seek, at its own cost, an
appropriate protective order or other remedy or waive compliance with the
provisions of this Agreement. If a Party seeks a protective order, the other
Party agrees to cooperate. If the Party seeking the protective order fails to
obtain the protective order or waive compliance with the relevant portions of
this Agreement, the other Party will disclose only that portion of information
concerning the Compound or Licensed Product that its legal counsel determines it
is required to disclose.

7.5. SEC Filings and Other Disclosures. Either Party may disclose the terms of
this Agreement to the extent required, in the reasonable opinion of such Party’s
legal counsel, to comply with Applicable Law, including the rules and
regulations promulgated by the United States Securities and Exchange Commission
or any equivalent governmental agency in any country in the world. Before
disclosing this Agreement or any of the terms hereof pursuant to this Section
7.5, the Parties will consult with one another on the terms of this Agreement to
be redacted in making any such disclosure, with the disclosing Party providing
as much advanced
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notice as is feasible under the circumstances, and giving consideration to the
comments of the other Party. Further, if a Party discloses this Agreement or any
of the terms hereof in accordance with this Section 7.5, such Party shall, at
its own expense, seek such confidential treatment of confidential portions of
this Agreement and such other terms, as may be reasonably requested by the other
Party.
7.6. Residual Knowledge Exception. Notwithstanding any provision of this
Agreement to the contrary, Residual Knowledge shall not be considered
Confidential Information for purposes of this Section 7.6.
7.7. Announcements. Except as may be expressly permitted under Section 7.5, and
except for OPKO’s press release which shall be in the form of Exhibit C attached
hereto, neither Party will make any public announcement regarding this Agreement
without the prior written approval of the other Party. For the sake of clarity,
nothing in this Agreement shall prevent Pfizer from making any scientific
publication or public announcement with respect to any Licensed Product under
this Agreement; provided, however, that, except as permitted under Section 7.3
or Section 7.4, Pfizer shall not disclose any of OPKO’s Confidential Information
in any such publication or announcement without obtaining OPKO’s prior written
consent to do so.
7.8. Publications.
7.8.1. Publications by Pfizer. During the Term, Pfizer shall submit to OPKO for
review and approval any proposed academic, scientific and medical publication or
public presentation that contains OPKO’s Confidential Information or relates to
a Compound or Licensed Product. Such review and approval will be conducted for
the purposes of preserving the value of the Licensed Technology and determining
whether any portion of the proposed publication or presentation containing
OPKO’s Confidential Information should be modified or deleted. Written copies of
such proposed publication or presentation required to be submitted hereunder
shall be submitted to OPKO no later than *** before submission for publication
or presentation (the “OPKO Review Period”). OPKO shall provide its comments with
respect to such publications and presentations within *** of its receipt of such
written copy. The OPKO Review Period may be extended for an additional *** in
the event OPKO can, within *** of receipt of the written copy, demonstrate
reasonable need for such extension, including for the preparation and filing of
patent applications. Pfizer will comply with standard academic practice
regarding authorship of scientific publications and recognition of the
contribution of other parties in any publication governed by this Section 7.8.1,
including International Committee of Medical Journal Editors standards regarding
authorship and contributions. For the sake of clarity, Pfizer’s obligation to
submit any publication to OPKO for review and approval under this Section 7.8.1
shall not apply to any publication that does not contain OPKO’s Confidential
Information or relate in any manner to the Compound or Licensed Product.
7.8.2. Publications by OPKO. During the Term, OPKO shall submit to Pfizer for
review and approval any proposed academic, scientific and medical publication or
public presentation that contains Pfizer’s Confidential Information or relates
to a Compound or Licensed Product. Such review and approval will be conducted
for the purposes of preserving the value of the Licensed Technology and
determining whether any portion of the proposed publication or presentation
containing the Pfizer’s Confidential Information should be modified or deleted.
Written copies of such proposed publication or presentation required to be
submitted hereunder shall be submitted to Pfizer no later than *** days before
submission for publication or presentation (the
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“Pfizer Review Period”). Pfizer shall provide its comments with respect to such
publications and presentations within *** days of its receipt of such written
copy. The Pfizer Review Period may be extended for an additional *** days in the
event Pfizer can, within of receipt of the written copy, demonstrate reasonable
need for such extension, including for the preparation and filing of patent
applications. OPKO will comply with standard academic practice regarding
authorship of scientific publications and recognition of the contribution of
other parties in any publication governed by this Section 7.8.2, including
International Committee of Medical Journal Editors standards regarding
authorship and contributions. For the sake of clarity, (x) OPKO shall not
include in its academic, scientific and medical publications and public
presentations any pre-clinical and clinical data and results relating to a
Compound or Licensed, including without limitation any such data and results
provided to Pfizer under this Agreement, without Pfizer’s prior written consent,
such consent not to be unreasonably withheld and (y) OPKO’s obligation to submit
any publication to Pfizer for review and approval under this Section 7.8.2 shall
not apply to any publication that does not contain Pfizer’s Confidential
Information or relate in any manner to the Compound or Licensed Product.
8. REPRESENTATIONS, WARRANTIES AND COVENANTS.
8.1. Mutual Representations and Warranties. Each of OPKO and Pfizer hereby
represents and warrants to the other Party, as of the Original Execution Date,
as of the Original Effective Date and as of the Amendment Execution Date that:
8.1.1. it is duly organized, validly existing and in good standing under the
laws of the jurisdiction of its organization;
8.1.2. the execution, delivery and performance of this Agreement by such Party
has been duly authorized by all requisite action under the provisions of its
charter, bylaws and other organizational documents, and does not require any
action or approval by any of its shareholders or other holders of its voting
securities or voting interests;
8.1.3. it has the power and authority to execute and deliver this Agreement and
to perform its obligations hereunder;
8.1.4. this Agreement has been duly executed and is a legal, valid and Binding
Obligation on each Party, enforceable against such Party in accordance with its
terms; and
8.1.5. the execution, delivery and performance by such Party of this Agreement
and its compliance with the terms and provisions hereof does not and will not
conflict with or result in a breach of or default under any Binding Obligation.
8.2. Mutual Covenants. Each of OPKO and Pfizer hereby covenants to the other
Party that:
8.2.1. from the Original Effective Date until the expiration or termination of
this Agreement, it will perform its obligations under this Agreement in
compliance in all material respects with Applicable Laws; and
8.2.2. with respect to any Licensed Products, payments or services provided
under this Agreement, such Party has not taken and will not during the Term take
any action, directly or indirectly, to offer, promise or pay, or authorize the
offer or payment of, any money or anything of value in order to improperly or
corruptly seek to influence
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any Government Official or any other person in order to gain an improper
advantage, and has not accepted, and will not accept in the future, such
payment.
8.3. OPKO Representations and Warranties. OPKO hereby represents and warrants to
Pfizer, as of the Original Execution Date and as of the Original Effective Date
that:
8.3.1. except as set forth in Schedule 8.3, OPKO and its Affiliates own all
right, title and interest to the Licensed Technology, all of which is clear of
any claims, liens, charges or encumbrances, including under any OPKO Third Party
Agreement, that would prevent OPKO from granting the rights it is granting to
Pfizer hereunder or conflict with the grant of those rights;
8.3.2. OPKO (including as necessary through appropriate licenses granted to OPKO
by its Affiliates) has the full right, power and authority to grant all of the
right, title and interest in the licenses and other rights granted or to be
granted to Pfizer, Pfizer’s Affiliates or Pfizer’s sublicensees under this
Agreement;
8.3.3. Schedule 1.98 sets forth a true and complete list of all Patent Rights
that are a part of the Licensed Technology owned or otherwise Controlled by OPKO
or its Affiliates that relate to the Compounds or Licensed Products, or their
manufacture or use, including in the case of Patent Rights that are licensed to
OPKO, the name of the owner(s) and licensor(s) and the agreement(s) providing
OPKO with Control, (b) each such Patent Right remains in full force and effect
and (c) OPKO or its Affiliates have timely paid, including within any extension
or grace periods, all filing and renewal fees payable with respect to such
Patent Rights;
8.3.4. to its knowledge, it has made available to Pfizer all material scientific
and technical information and safety and efficacy information in its possession
with respect to the Compounds and Licensed Products;
8.3.5. to its knowledge, no Third Party has challenged or threatened in writing
to challenge the inventorship, Control, right to use, scope, validity or
enforceability of any Licensed Patent Right (including, by way of example,
through the institution or written threat of institution of interference,
derivation, post-grant review, opposition, nullity or similar invalidity
proceedings before the United States Patent and Trademark Office or any
analogous foreign Governmental Authority);
8.3.6. it has complied with all Applicable Laws, including any disclosure
requirements, in connection with the filing, prosecution and maintenance of the
Licensed Patent Rights;
8.3.7. except as expressly disclosed in Schedule 8.3, to its knowledge, OPKO and
its Affiliates have independently developed all Licensed Know-How or otherwise
have a valid right to use, and to permit Pfizer, Pfizer’s Affiliates and
Pfizer’s permitted sublicensees to use, the Licensed Know-How for all permitted
purposes under this Agreement;
8.3.8. OPKO and its Affiliates have obtained, from all inventors of Licensed
Technology, valid and enforceable agreements assigning to OPKO each such
inventor’s entire right, title and interest in and to all such Licensed
Technology;
8.3.9. except as disclosed in Schedule 8.3, to its knowledge, other than
ordinary course governmental rights that apply to research performed with
federal state or local
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institutions, no Licensed Technology is subject to any funding agreement with
any government or Governmental Authority;
8.3.10. except as expressly disclosed in Schedule 8.3, neither OPKO nor any of
its Affiliates are party to or otherwise subject to any agreement or arrangement
which limits the ownership or licensed rights of Pfizer or its Affiliates with
respect to, or limits the ability of Pfizer or its Affiliates to grant a
license, sublicense or access, or provide or provide access or other rights in,
to or under, any Intellectual Property Right or material (including any Patent
Right, Know-How or other data or information) as related to the Compound or
Licensed Product, in each case, that would, but for such agreement or
arrangement, be included in the rights licensed or assigned to Pfizer or its
Affiliates pursuant to this Agreement;
8.3.11.  there are no OPKO Third Party Agreements, other than the OPKO Third
Party Agreements disclosed in Schedule 8.3 (each, a “Disclosed Third Party
Agreement”), true and complete copies of which have been made available to
Pfizer, pursuant to which (a) any Third Party has any right, title or interest
in or to, or any license or covenant not to sue under, any Licensed Technology
licensed hereunder, or (b) rights granted by or to OPKO or its Affiliates
conflict with any right or license granted to Pfizer or its Affiliates
hereunder;
8.3.12. to its knowledge, neither the Compound, nor the Development, Manufacture
or manufacture and use of the Compound as conducted by OPKO prior to the
Original Execution Date infringes any then-issued Patent Right of a Third Party;
8.3.13. to its knowledge, the parties to the Disclosed Third Party Agreements
are in compliance in all material respects with all Disclosed Third Party
Agreements except to the extent such noncompliance would not conflict with any
right or license granted to Pfizer or its Affiliates hereunder;
8.3.14. to its knowledge, OPKO, its Affiliates and all other Third Parties that
have conducted or have otherwise provided materials, support or services for any
ongoing Trials are and have been in material compliance with all Applicable
Laws, including, where applicable, compliance with GCP, and are and have been in
material compliance with any other agreed upon quality standards, in each case
at every stage during the said Trials (including protocol and database
development, Trial site feasibility and initiation, subject enrollment, Trial
study conduct, analysis and reporting) and have not been the subject of any
regulatory enforcement action by any Regulatory Authority, or of any
circumstances that would give rise to any such Third Parties being the subject
of any regulatory enforcement action by any Regulatory Authority;
8.3.15. OPKO is not, and, to its knowledge, no (a) current licensor or (b)
clinical research investigator, institution or other Third Party acting on
behalf of OPKO in connection with a Trial under a written agreement for services
or rights related to Licensed Product (in each case, as applicable) is debarred
by any Regulatory Authority or the subject of debarment proceedings by any
Regulatory Authority and, in the course of the Development of any Compound, OPKO
has not used, and, to its knowledge, (i) no current licensor nor (ii) any
clinical research investigators, institutions or other Third Parties acting on
behalf of OPKO in connection with a Trial (in each case, as applicable) has
used, any employee or consultant that is debarred by any Regulatory Authority
or, to OPKO’s knowledge, is the subject of debarment proceedings by any
Regulatory Authority;
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8.3.16. to its knowledge, there is no (a) claim, demand, suit, proceeding,
arbitration, inquiry, investigation or other legal action of any nature, civil,
criminal, regulatory or otherwise, pending or, to its knowledge, threatened
against OPKO or any of its Affiliates or (b) judgment or settlement against or
owed by OPKO or any of its Affiliates, in each case in connection with the
Licensed Technology, any Compound or any Licensed Product or relating to the
transactions contemplated by this Agreement; and
8.3.17. (a) Invitrogen and its successors have no claim on or other interest in
the MOD-4023 cells or any use thereof, (b) other than the license that is in
place between OPKO or its Affiliates and Invitrogen or its successor relating to
DG44 Materials, no additional license is required from Invitrogen or its
successors in order to permit the use of the DG44 Materials or the MOD-4023
cells in commercial bioproduction applications, including for commercial
production of Licensed Products, and (c) the only further Third Party
intellectual property license that needs to be put in place in order enable the
use of the DG44 Materials or the MOD-4023 cells in commercial bioproduction
applications, including for commercial production of Licensed Products, without
infringing the Intellectual Property Rights of any Third Party is a license for
use of these materials in commercial bioproduction applications to be obtained
from Lawrence Chasin and Gail Urlaub Chasin.
Reference to “its knowledge” in any of the above provisions of this Section 8.3
means actual knowledge of senior management of OPKO and its Affiliates or other
employees of OPKO and its Affiliates responsible for patent matters after
reasonable and due inquiry.

8.4. OPKO Covenants. In addition to the covenants made by OPKO elsewhere in this
Agreement, OPKO hereby covenants to Pfizer that, from the Original Effective
Date until expiration or termination of this Agreement, other than in connection
with the Agreement:
8.4.1. it shall not, and shall cause its Affiliates not to, incur or permit to
exist, with respect to any Licensed Technology related to the Compound or any
Licensed Product, any lien, encumbrance, charge, security interest, mortgage,
liability, assignment, grant of license or other Binding Obligation that is or
would be inconsistent with the licenses and other rights granted to Pfizer or
its Affiliates under this Agreement;
8.4.2. it will (a) not enter into any OPKO Third Party Agreement that adversely
affects (i) the rights granted to Pfizer, Pfizer’s Affiliates or sublicensees
hereunder or (ii) OPKO’s ability to fully perform its obligations hereunder; (b)
not amend or otherwise modify any OPKO Third Party Agreement (including any
Disclosed Third Party Agreement) or consent or waive rights with respect thereto
in any manner that (i) adversely affects the rights granted to Pfizer or
Pfizer’s Affiliates or sublicensees hereunder or (ii) OPKO’s ability to fully
perform its obligations hereunder; (c) promptly furnish Pfizer with true and
complete copies of all amendments to the Disclosed Third Party Agreements and
OPKO Third Party Agreements, relating to a Trial and related amendments executed
following the Original Effective Date; (d) remain, and cause its Affiliates to
remain, in compliance in all material respects with all OPKO Third Party
Agreements relating to a Trial (including Disclosed Third Party Agreements); and
(e) furnish Pfizer with copies of all notices received by OPKO or its Affiliates
relating to any alleged breach or default by OPKO or its Affiliates under any
OPKO Third Party Agreement relating to a Trial (including and Disclosed Third
Party Agreement) within five (5) Business Days after receipt thereof;
8.4.3. where OPKO’s or its Affiliates’ ownership of all right, title and
interest to the Licensed Technology is based upon or depends on a sequence of
historical transfers
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of title to any of the Licensed Technology (i.e. chain of title to the Licensed
Technology) being valid, effective and free from defects and other problems, if
at any time there is a potential defect with the validity or effectiveness in
such transfers or other problems in such chain of title, then OPKO and its
Affiliates shall, at their expense, with urgency and diligence make any and all
corrections and clarifications, including preparing any documents and obtaining
any necessary Third Party signatures and consents, as may be necessary,
including filing such documents in any patent office as appropriate, to remedy
any such problems and to restore such chain of title;
8.4.4. it will not enter into or otherwise allow itself or its Affiliates to be
subject to any agreement or arrangement that limits the ownership or licensed
rights of Pfizer or its Affiliates with respect to, or limits the ability of
Pfizer or its Affiliates to grant a license, sublicense or access, or provide or
provide access or other rights in, to or under, any existing Licensed Technology
or material (including any Patent Right, Know-How or other data or information)
as related to the Compound or Licensed Product, in each case, that would, but
for such agreement or arrangement, be included in the rights licensed or
assigned to Pfizer or its Affiliates pursuant to this Agreement;
8.4.5. unless otherwise agreed by the Parties, it will maintain valid and
enforceable agreements with all Persons acting by or on behalf of OPKO or its
Affiliates under this Agreement that require such Persons to assign to OPKO
their entire right, title and interest in and to all Licensed Technology as
related to the Compound or Licensed Product;
8.4.6. OPKO and its Affiliates shall, at their sole expense, timely satisfy in
full any and all obligations owed to Israel’s Office of the Chief Scientist
within the Ministry of Economy (“OCS”), including in relation to any grants OCS
previously provided to OPKO or its Affiliates, in each case relating to the
Licensed Products and/or the Development thereof; and
8.4.7. Promptly following the Original Effective Date, OPKO shall obtain, at its
cost and expense, a license for commercial bioproduction applications to utilize
the DG44 cell line materials used by OPKO and its Affiliates in relation to the
Licensed Products (“DG44 Materials”), which license shall be obtained in such a
manner that it extends to each of Rentschler, Pfizer and any designee of OPKO in
the event of a termination of this Agreement or a *** hereunder.
8.5. ***
8.5.1. ***
8.5.2. ***
8.6. Compliance with Law and Ethical Business Practices. In addition to the
other representations, warranties and covenants made by each Party elsewhere in
this Agreement, each Party represents and warrants or covenants and agrees, as
applicable, with the other Party that during the Term:
8.6.1. it is licensed, registered, or qualified under all Applicable Laws to do
business, and has obtained such licenses, consents, authorizations or completed
such registrations or made such notifications as may be necessary or required by
Applicable Law to provide any products, goods or services encompassed within
this Agreement, and
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providing such products, goods or services is not inconsistent with any other
obligation of such Party;
8.6.2. in conducting its activities hereunder, such Party will and will cause
its Affiliates and, to the extent of its legal right to do so, use reasonable
efforts to cause its other Representatives to comply in all material respects
with all Applicable Laws and accepted pharmaceutical industry business
practices, including, to the extent applicable to such Party and each of its
Affiliates and other Representatives: the Federal Food, Drug, and Cosmetic Act
(21 U.S.C. § 301, et seq.), the Anti-Kickback Statute (42 U.S.C. § 1320a-7b),
the Civil Monetary Penalty Statute (42 U.S.C. § 1320a-7a), the False Claims Act
(31 U.S.C. § 3729 et seq.), comparable state statutes, the regulations
promulgated under all such statutes, and the regulations issued by the FDA;
8.6.3. with respect to any products, payments or services provided under this
Agreement, it has not taken and will not during the Term take any action
directly or indirectly to offer, promise or pay, or authorize the offer or
payment of, any money or anything of value in order to improperly or corruptly
seek to influence any Government Official or any other person in order to gain
an improper advantage, and has not accepted, and will not accept in the future,
such payment;
8.6.4. it complies with the laws and regulations of the countries where it
operates, including anti-bribery and anti-corruption laws, accounting and record
keeping laws, and laws relating to interactions with healthcare professionals or
healthcare providers and Government Officials;
8.6.5. to its knowledge, it and each of its Affiliates has been and will, for
the Term, be in compliance with all applicable global trade laws, including
those related to import controls, export controls or economic sanctions, and
such Party will cause each of its Affiliates to remain in compliance with the
same during the Term;
8.6.6. to its knowledge, except to the extent permissible under United States
law, neither it nor any of its Affiliates has, on its own behalf or acting on
behalf of any other Person, directly or indirectly engaged with, and will not
for the Term, directly or indirectly engage in any transactions with, or
otherwise deal with, any country or Person targeted by United States, European
Union, United Kingdom or other relevant economic sanctions laws in connection
with any activities related to such Party’s interaction with the other Party,
including those contemplated under this Agreement; and
8.6.7. it is, as between the Parties, solely responsible for ensuring Compliance
by it and its Affiliates.
8.7. Representation by Legal Counsel. Each Party hereto represents that it has
been represented by legal counsel in connection with this Agreement and
acknowledges that it has participated in the drafting hereof. In interpreting
and applying the terms and provisions of this Agreement, the Parties agree that
no presumption shall exist or be implied against the Party which drafted such
terms and provisions.
8.8. Disclaimer. THE REPRESENTATIONS AND WARRANTIES OF EACH PARTY IN THIS
AGREEMENT ARE IN LIEU OF ANY OTHER REPRESENTATIONS AND WARRANTIES, EXPRESS OR
IMPLIED, INCLUDING ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR ANY IMPLIED
WARRANTIES OF FITNESS FOR A PARTICULAR PURPOSE, ALL OF WHICH ARE HEREBY
SPECIFICALLY EXCLUDED AND DISCLAIMED.
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9. TERM AND TERMINATION.
9.1. Term. The term of this Agreement (the “Term”) will commence on the Original
Execution Date and end as follows: (a) if the Royalty Term expires prior to the
initiation of a Profit Share Term, the Term shall terminate at end of the
Royalty Term; (b) if a Profit Share Term begins prior to the expiration of the
Royalty Term, the Term shall terminate *** in the Territory, unless, in either
case of (a) and (b), this Agreement is terminated earlier as permitted in this
Article 9.
9.2. Termination for Uncured Material Breach. Either Party may terminate this
Agreement for cause at any time during the Term by giving written notice to the
other Party in the event that such other Party commits a material breach of its
obligations under this Agreement and such material breach remains uncured for
*** days (or *** days for any payment breach) from the date of receipt of such
notice by the breaching Party; provided, however, that if any breach is not
reasonably curable within *** days and if the breaching Party is making a bona
fide effort to cure such breach, such termination shall be delayed for a time
period to be agreed by both Parties in order to permit the breaching Party a
reasonable period of time to cure such breach. If the breaching Party disputes
in good faith that it has materially breached one of its obligations under this
Agreement, termination shall not take effect pending resolution of such dispute
pursuant to Section 11.13 so long as Commercialization of Genotropin Products
and Licensed Products continues in at least all countries in which
Commercialization was ongoing as of the date of receipt of written notice of
breach by the breaching Party. If, as a result of the application of such
dispute resolution procedures, the breaching Party is determined to be in
material breach of one or more of its obligations under this Agreement, then if
the breaching Party fails to complete the actions specified to cure such breach
within *** days (or *** days for any payment breach) after such ruling, then the
complaining Party may terminate this Agreement upon written notice to the
breaching Party.
9.3. Termination at Will. Upon delivery of at least *** prior written notice to
OPKO, Pfizer shall have the right to terminate this Agreement for any reason (a)
in its entirety or (b) with respect ***. For clarity, termination by Pfizer of
the last remaining *** under this Agreement shall be deemed to be termination of
this Agreement in its entirety.
9.4. Termination for a Bankruptcy Event.
9.4.1. Termination Right. Each Party shall have the right to terminate this
Agreement in the event of a Bankruptcy Event with respect to the other Party.
“Bankruptcy Event” means the occurrence of any of the following: (a) the
institution of any bankruptcy, receivership, insolvency, reorganization or other
similar proceedings by or against a Party under any bankruptcy, insolvency, or
other similar law now or hereinafter in effect, including any section or chapter
of the United States Bankruptcy Code, as amended, or under any similar laws or
statutes of the United States or any state thereof (the “Bankruptcy Code”),
where in the case of involuntary proceedings such proceedings have not been
dismissed or discharged within ninety (90) days after they are instituted, (b)
the filing of an insolvency proceeding or making of an assignment for the
benefit of creditors or the admittance by a Party of any involuntary debts as
they mature, (c) the institution of any reorganization, arrangement or other
readjustment of debt plan of a Party not involving the Bankruptcy Code, (d)
appointment of a receiver for all or substantially all of a Party’s assets, or
(e) any corporate action taken by the board of directors of a Party in
furtherance of any of the foregoing actions.
9.4.2. Rights to Intellectual Property. All rights and licenses granted under or
pursuant to this Agreement by OPKO are, and shall otherwise be deemed to be, for
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purposes of Section 365(n) of the Bankruptcy Code, licenses of rights to
“intellectual property” as defined under Section 101 of the Bankruptcy Code. The
Parties agree that Pfizer, as licensee of intellectual property under this
Agreement, shall retain and may fully exercise all of its rights and elections
under the Bankruptcy Code. The Parties further agree that in the event of a
rejection of this Agreement by OPKO in any bankruptcy proceeding by or against
OPKO under the Bankruptcy Code or foreign equivalent, (a) Pfizer shall be
entitled to a complete duplicate of (or complete access to, as appropriate) any
such intellectual property and all embodiments of such intellectual property,
which, if not already in Pfizer’s possession, shall be promptly delivered to it
upon Pfizer’s written request therefor, and (b) OPKO shall not interfere with
Pfizer’s rights to intellectual property and all embodiments of intellectual
property, and shall assist and not interfere with Pfizer in obtaining
intellectual property and all embodiments of intellectual property from another
entity. The term “embodiments” of intellectual property includes all tangible,
intangible, electronic or other embodiments of rights and licenses hereunder,
including all compounds and products embodying intellectual property, Licensed
Products, filings with Regulatory Authorities and related rights, and Licensed
Technology.
9.5. Effects of Expiration or Termination.
9.5.1. Partial Termination. In case of termination of this Agreement, not in its
entirety, but with respect to only ***, by Pfizer pursuant to Section 9.3 (a
“Partial Termination” and *** in which such Partial Termination occurs, a
“***”), then the effects of termination described under Section 9.5.2 shall only
apply to the ***, and this Agreement shall remain in full force and effect in
accordance with its terms in *** of the Territory.
9.5.2. Termination by OPKO for Uncured Material Breach or Bankruptcy Event;
Termination by Pfizer at Will. In the event that OPKO terminates this Agreement
pursuant to Section 9.2 or Section 9.4, or Pfizer terminates this Agreement in
whole or in part pursuant to Section 9.3, the following will apply in respect of
the *** or Agreement, as the case may be.
(a) License. Effective upon the date of termination for the Agreement or each
***, Pfizer hereby grants to OPKO a fully ***, non-exclusive, perpetual,
irrevocable, sublicenseable right and license under (i) the Pfizer Developed IP
and (ii) any other Patent Rights and Know-How Controlled by Pfizer and its
Affiliates as of the effective date of termination that is necessary to continue
the Development, Manufacture and Commercialization of Compounds and Licensed
Products, in each case, to use, have used, Develop, have Developed, Manufacture,
have Manufactured, Commercialize, and have Commercialized Compounds and Licensed
Products; provided, that upon request of OPKO, the Parties shall negotiate in
good faith ***. Neither Party will be obligated to enter into any transaction
described in this Section 9.5.2(a), and neither Party will have any liability to
the other for failure to do so. *** OPKO shall be responsible for any royalties
or other payments payable to Third Parties with respect to the use by OPKO and
its Affiliates and sublicensees of any Patent Rights or Know-How licensed to
OPKO under this Section 9.5.2(a).
(b) Marks. To the extent that Pfizer is Commercializing any Licensed Product
under any Trademark that is neither (i) used for any other products in Pfizer’s
portfolio, nor (ii) confusingly similar to any other trade mark used for any
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other products in Pfizer’s portfolio, Pfizer shall, upon OPKO’s request, assign
such Trademark to OPKO. As part of the termination transition plan, the Parties
shall reach agreement on commercially reasonable terms for procedures and
obligations to address functional areas in which each Party’s respective
Licensed Product activities inside and outside of the Territory following
termination of *** may have an impact on one another, including
pharmacovigilance, coordination of brand messaging and coordination on any
further Development efforts.
(c) Transition. Prior to the effective date of any termination or partial
termination of this Agreement, the Parties shall negotiate in good faith and
agree upon an outline and estimated schedule for transition of Intellectual
Property Rights and Licensed Products to OPKO, to be reflected in a commercially
reasonable termination transition plan and, if appropriate, a transition
agreement, to seek to minimize any disruption to the Development or
Commercialization of the Licensed Product (including therapy and coverage for
patients, patient support activities, and pharmacovigilance reporting). The
termination transition plan, and any transition agreement, shall provide for
undertaking Commercially Reasonable Efforts for development and regulatory
activities, support in commercialization activities, and such other matters as
the parties may agree, including, if appropriate, a governance structure to
allow for decision-making to be made on transition issues. Pfizer shall use
diligent efforts to cooperate with OPKO or its designee to effect a smooth and
orderly transition, which transition shall not exceed ***, except with respect
to supply of Licensed Product which shall continue for the period contemplated
herein.
(d) Ongoing Trials. In the event of: (x) a termination of this Agreement in its
entirety, with respect to ongoing clinical trials and investigator-initiated
trials involving a Licensed Product or related Device supported, directly or
indirectly, by Pfizer or its Affiliates; or (y) in the event of a termination of
this Agreement in part by Pfizer pursuant to Section 9.3, with respect to those
ongoing clinical trials and investigator-initiated trials involving a Licensed
Product or related Device supported, directly or indirectly, by Pfizer or its
Affiliates that relate only to a country or countries that are located in the
*** so terminated; the Parties will, with respect to such trials:
(i) Within *** days of the date of the notice of termination, Pfizer will
provide OPKO with a list of ongoing clinical trials and investigator-initiated
trials involving a Licensed Product or related Device supported, directly or
indirectly, by Pfizer or its Affiliates. The trial listing shall include
material details of the trials such as protocol summary, dates, sites, budget
expended and estimated budget remaining, number of patients, current enrollment
and safety issues. Pfizer shall promptly answer any questions of OPKO as to the
status or details of any such trial. Prior to the date of termination, OPKO will
notify Pfizer as to any trial for which OPKO wishes to assume responsibility
and, Pfizer shall, at OPKO’s cost and expense for activities after termination,
complete such Trial. Notwithstanding the foregoing, Pfizer may prematurely
suspend or terminate any such Trial if (A) a priori protocol defined stopping
rules are met for safety or efficacy or (B) unacceptable safety signals are
observed by Pfizer or a data and safety monitoring board with respect to the
Licensed Product that present an unacceptable risk to patients participating in
such trials.
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(ii) With respect to any ongoing Trials involving a Licensed Product for which
OPKO has notified Pfizer prior to the effective date of termination that it
wishes to assume responsibility (provided that, with ***, OPKO shall be required
to assume responsibility for such Trial and the provisions of this Section
9.5.2(d)(ii) shall apply to such Trial) (A) each Party shall cooperate with the
other Party to facilitate the orderly transfer to OPKO of the conduct of such
Trials as soon as reasonably practicable after the effective date of
termination, (B) until such time as the conduct of such Trials has been
successfully transferred to OPKO, Pfizer shall continue such Trials, (C) between
the effective date of termination and the date on which the conduct of such
Trials has been successfully transferred to OPKO, OPKO shall be responsible for,
and shall reimburse Pfizer with respect to, all costs and expenses reasonably
incurred by Pfizer in the conduct of such Trials, and (D) following the date on
which the conduct of such Trials has been successfully transferred to OPKO, OPKO
shall be solely responsible for all costs and expenses of such ongoing Trials.
(e) Assignment of Filings and Marketing Approvals. At OPKO’s option, which shall
be exercised by written notice to Pfizer, to the extent permitted under
Applicable Laws, Pfizer shall assign or cause to be assigned to OPKO or its
designee (or to the extent not so assignable, Pfizer shall take all reasonable
actions to make available to OPKO or its designee the benefits of), at no cost
to OPKO, any and all regulatory filings made with and all Regulatory Approvals
obtained from the Regulatory Authorities in the Territory specifically relating
to the Licensed Products, including, without limitation, any BLAs, MAAs, PMDAs,
Price Approvals and third-party reimbursement approvals, in all such cases, only
to the extent it is legally permissible to so transfer such items.
(f) Transfer of Know How. Pfizer shall promptly provide to OPKO, at no cost to
OPKO, all Know-How, materials, and other development data specifically relating
to the Licensed Products, provided, that Pfizer shall be entitled to retain
copies of such items for legal archival and regulatory purposes. Pfizer
shall deliver to OPKO (i) all clinical data and information in Pfizer’s
possession or control relating solely to Licensed Product, including for
clarity, manufacturing data, if any (subject to the proviso at the end of this
sentence), in the same form in which Pfizer maintains such data and (ii) in the
same form in which Pfizer maintains such items, copies of all reports, records,
regulatory correspondence and other materials in Pfizer’s possession or control
relating solely to the clinical development of Licensed Product, including, if
applicable, any information contained in the global safety database established
and maintained by Pfizer.
(g) Rights of Reference. Pfizer shall grant to OPKO a “Right of Reference,” as
that term is defined in 21 C.F.R. § 314.3(b) (or any analogous Applicable Law
recognized outside of the United States), with respect to development data and
regulatory filings transferred to OPKO pursuant to clauses (e) and (f) above.
(h) Supply of Licensed Product.
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(i) In the event of a termination of a *** or this Agreement in its entirety,
except to the extent that Pfizer continues to supply Licensed Product to OPKO
following a partial termination pursuant to subsection (ii) below, Pfizer shall
continue to supply OPKO after the effective date of termination with OPKO’s
requirements of clinical and commercial quantities of Compound and Licensed
Products, pursuant to a supply agreement to be negotiated in good faith by the
Parties on “commercially reasonable terms,” which agreement will remain in
effect until the earlier of (a) the *** anniversary of the effective date of
termination, and (b) such time as OPKO or a Third Party manufacturer engaged by
OPKO is capable of supplying OPKO with its requirements of clinical and
commercial quantities of Compound and Licensed Products (the “Supply Period”);
provided, however, that OPKO must use its commercially reasonable best efforts
to supply or have supplied by a Third Party, Compound and Licensed Products as
soon as reasonably practicable after the effective date of such termination. In
addition, Pfizer shall assign any Third Party contracts to which it is a party
relating to the supply or Commercialization of Licensed Product to OPKO and use
Commercially Reasonable Efforts to cause such Third Parties to continue to
supply to OPKO the same supplies and services then utilized in the Development,
Manufacture and Commercialization of the Licensed Product. In the event Pfizer
is restricted from assigning such Third Party contracts, Pfizer shall use
Commercially Reasonable Efforts to maintain such Third Party Agreements for the
benefit of OPKO until the end of the Supply Period. Solely for purposes of this
Subsection 9.5.2(h)(i) “commercially reasonable terms” means, with respect to
clinical supplies of Compound and Licensed Products, *** prior to the *** of
effective date of termination, *** for the ***, and *** after the *** of the
effective date of termination, to be set forth in the supply agreement between
the Parties. Prior to termination of the supply term, if requested by OPKO,
Pfizer shall cooperate with OPKO in building a reasonable safety stock of
Licensed Products.
(ii) In the event of a termination of this Agreement in part by Pfizer pursuant
to Section 9.3, Pfizer may elect, in its sole discretion, to continue to supply
OPKO after the effective date of termination with OPKO’s requirements of
clinical and commercial quantities of Compound and Licensed Products, pursuant
to a supply agreement to be negotiated in good faith by the Parties on
“commercially reasonable terms,” provided, however, that (A) Pfizer shall
provide notice to OPKO of its decision with regard to post-termination supply,
pursuant to this Subsection 9.5.2(h)(ii), no fewer than *** days prior to the
effective date of termination, and (B) ***. Solely for purposes of this
Subsection 9.5.2(h)(ii) “commercially reasonable terms” means, with respect to
clinical supplies of Compound and Licensed Products, *** for such supplies, and
with respect to commercial supplies means Pfizer’s ***.
(i) Existing Inventory. Notwithstanding anything in this Agreement to the
contrary, except in the event of termination by OPKO for Pfizer’s uncured
material breach, Pfizer and its Affiliates shall have the right to continue to
sell their existing inventory of Licensed Products for a period not to exceed
*** days
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after the effective date of such termination, and OPKO shall continue to receive
royalties and gross profit payments with respect to such sales.
9.5.3. Termination by Pfizer for Cause or Bankruptcy Event.
(a) Partial Termination. In the event that Pfizer terminates this Agreement
pursuant to Section 9.2 or Section 9.4 with respect to any Licensed Product ***
in the Territory: (i) all licenses granted under this Agreement by OPKO to
Pfizer with respect to such Licensed Product in such *** shall become fully ***,
perpetual, irrevocable *** and (ii) except as otherwise expressly provided
herein, all other rights and obligations of each Party with respect to such
Licensed Product in such *** shall cease.
(b) Complete Termination. In the event that Pfizer terminates this Agreement in
its entirety pursuant to Section 9.2 or Section 9.4, (i) all licenses granted
under this Agreement by OPKO to Pfizer shall become fully ***, perpetual,
irrevocable *** and (ii) except as otherwise expressly provided herein, all
other rights and obligations of each Party with respect to such Licensed Product
in such *** shall cease.
9.5.4. Confidential Information. Following any termination of this Agreement,
each of Pfizer and OPKO shall, upon request of the other Party, return or
destroy all Confidential Information of such Party, disclosed to it pursuant to
this Agreement, including all copies and extracts of documents, as promptly as
practicable following receipt of such request, except that one (1) copy may be
kept for the purpose of complying with continuing obligations under this
Agreement.
9.5.5. Accrued Obligations. Expiration or termination of this Agreement, in
whole or part, for any reason (i) shall be without prejudice to OPKO’s right to
receive all royalties and Profit Share Payments accrued under Sections 5.3
and 5.4 prior to the effective date of such termination and any other payments
due hereunder that have accrued prior to the effective date of such termination,
(ii) shall be without prejudice to any other remedies that either Party may
otherwise have, and (iii) shall not release a Party hereto from any
indebtedness, liability or other obligation incurred hereunder by such Party
prior to the date of termination or expiration.
9.5.6. Survival. Expiration or termination of this Agreement shall not relieve
the Parties of any obligation accruing hereunder prior to such expiration or
termination. Without limiting the foregoing, the following sections, together
with this Section 9.5.6 and any sections that expressly survive, shall survive
expiration or termination of this Agreement for any reason: Sections 1
(Definitions), 2.4 (Licenses to Pfizer Developed IP), 5 (Payments), 5.8
(Inspection of Records), 5.10 (No Guarantee of Success), 6.1.1 (Pre-Existing
IP), 6.1.2 (Developed IP), 7 (Confidentiality), 9.5 (Effects of Expiration or
Termination), 10.1 (Limitation of Liability), 10.2 (Indemnification by Pfizer),
10.3 (Indemnification by OPKO), 10.4 (Procedure) and 11 (Miscellaneous).
10. LIMITATION OF LIABILITY, INDEMNIFICATION AND INSURANCE.
10.1. Limitation of Liability. EXCEPT WITH RESPECT TO LIABILITY ARISING FROM A
BREACH OF ARTICLES 6 AND 7, FROM ANY WILLFUL MISCONDUCT OR INTENTIONALLY
WRONGFUL ACT, OR TO THE EXTENT SUCH PARTY MAY BE REQUIRED TO INDEMNIFY THE OTHER
PARTY UNDER THIS ARTICLE 10, IN NO EVENT WILL EITHER PARTY OR ITS
REPRESENTATIVES BE LIABLE UNDER THIS
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AGREEMENT FOR ANY SPECIAL (ONLY AS RESPECTS INDIRECT, INCIDENTAL OR
CONSEQUENTIAL DAMAGES OR LOST PROFITS OR REVENUE), INDIRECT, INCIDENTAL,
CONSEQUENTIAL OR PUNITIVE DAMAGES, WHETHER IN CONTRACT, WARRANTY, TORT,
NEGLIGENCE, STRICT LIABILITY OR OTHERWISE, OR LOSS OF PROFITS OR REVENUE
SUFFERED BY THE OTHER PARTY OR ANY OF ITS REPRESENTATIVES. Without limiting the
generality of the foregoing, “consequential damages” will be deemed to include,
and neither Party will be liable to the other Party or any of such other Party’s
Representatives or stockholders for, any damages based on or measured by loss of
projected or speculative future sales of the Licensed Products, any Regulatory
Milestone Payment due upon any unachieved Regulatory Milestone under Section
5.2, any unearned Net Sales or Franchise Net Sales, any unearned royalties or
gross profit payments under Section 5.3 or Section 5.4 or any other unearned,
speculative or otherwise contingent payments provided for in this Agreement or
other speculative costs or savings related to the Development or
Commercialization of Licensed Products.
10.2. Indemnification by Pfizer. Pfizer will indemnify, defend and hold harmless
OPKO, each of its Affiliates, and each of its and its Affiliates’ employees,
officers, directors and agents (each, an “OPKO Indemnified Party”) from and
against any and all liability, loss, damage, expense (including reasonable
attorneys’ fees and expenses) and cost (collectively, a “Liability”) that the
OPKO Indemnified Party may be required to pay to one or more Third Parties to
the extent resulting from or arising out of:
10.2.1. the negligence or willful misconduct of Pfizer or its Affiliates or
sublicensees in connection with this Agreement;
10.2.2. Manufacture, Development, Commercialization or use of any Licensed
Product by, on behalf of, or under the authority of, Pfizer (including by any
OPKO Indemnified Party), other than (i) claims by Third Parties relating to
patent infringement arising out of the exercise of rights under the Licensed
Patent Rights, (ii) claims by Third Parties relating to misappropriation of
trade secrets arising out of the exercise of rights under the Licensed Know-How,
or (iii) claims for which OPKO is required to indemnify Pfizer pursuant to
Section 10.3; or
10.2.3. the material breach by Pfizer of any of its representations, warranties
or covenants set forth in Article 8, except, in each case, to the extent caused
by the breach, negligence, recklessness or intentional acts of OPKO or any OPKO
Indemnified Party.
10.3. Indemnification by OPKO. OPKO will indemnify, defend and hold harmless
Pfizer, its Affiliates, sublicensees, contractors and, distributors, and each of
its and their respective employees, officers, directors and agents (each, a
“Pfizer Indemnified Party”) from and against any and all Liabilities that the
Pfizer Indemnified Party may be required to pay to one or more Third Parties to
the extent resulting from or arising out of:
10.3.1. the negligence or willful misconduct of OPKO or its Affiliates in
connection with this Agreement;
10.3.2. the material breach by OPKO of any of its representations, warranties or
covenants set forth in Article 8, except, in each case, to the extent caused by
the breach, negligence, recklessness or intentional acts of Pfizer or any Pfizer
Indemnified Party; or
10.3.3. OPKO’s misappropriation of trade secrets, proprietary materials, and/or
patentable subject matter, in each case owned or Controlled by a Third Party in
relation to
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the Development or Manufacture of the Licensed Product at any time prior to the
Amendment Effective Date.
10.4. Procedure.
10.4.1. Notice. Each Party will notify the other Party in writing in the event
it becomes aware of a claim for which indemnification may be sought hereunder.
In the event that any Third Party asserts a claim or other proceeding (including
any governmental investigation) with respect to any matter for which a Party
(the “Indemnified Party”) is entitled to indemnification hereunder (a “Third
Party Claim”), then the Indemnified Party shall promptly notify the Party
obligated to indemnify the Indemnified Party (the “Indemnifying Party”) thereof;
provided, however, that no delay on the part of the Indemnified Party in
notifying the Indemnifying Party shall relieve the Indemnifying Party from any
obligation hereunder unless (and then only to the extent that) the Indemnifying
Party is prejudiced thereby.
10.4.2. Control. The Indemnifying Party shall have the right, exercisable by
notice to the Indemnified Party within ten (10) Business Days after receipt of
notice from the Indemnified Party of the commencement of or assertion of any
Third Party Claim, to assume direction and control of the defense, litigation,
settlement, appeal or other disposition of the Third Party Claim (including the
right to settle the claim solely for monetary consideration) with counsel
selected by the Indemnifying Party and reasonably acceptable to the Indemnified
Party; provided that (a) the Indemnifying Party has sufficient financial
resources, in the reasonable judgment of the Indemnified Party, to satisfy the
amount of any adverse monetary judgment that is sought, (b) the Third Party
Claim seeks solely monetary damages and (c) the Indemnifying Party expressly
agrees in writing that as between the Indemnifying Party and the Indemnified
Party, the Indemnifying Party shall be solely obligated to satisfy and discharge
the Third Party Claim in full (the conditions set forth in clauses (a), (b) and
(c) above are collectively referred to as the “Litigation Conditions”). Within
ten (10) Business Days after the Indemnifying Party has given notice to the
Indemnified Party of its exercise of its right to defend a Third Party Claim,
the Indemnified Party shall give notice to the Indemnifying Party of any
objection thereto based upon the Litigation Conditions. If the Indemnified Party
reasonably so objects, the Indemnified Party shall continue to defend the Third
Party Claim, at the expense of the Indemnifying Party, until such time as such
objection is withdrawn. If no such notice is given, or if any such objection is
withdrawn, the Indemnifying Party shall be entitled, at its sole cost and
expense, to assume direction and control of such defense, with counsel selected
by the Indemnifying Party and reasonably acceptable to the Indemnified Party.
During such time as the Indemnifying Party is controlling the defense of such
Third Party Claim, the Indemnified Party shall cooperate, and shall cause its
Affiliates and agents to cooperate upon request of the Indemnifying Party, in
the defense or prosecution of the Third Party Claim, including by furnishing
such records, information and testimony and attending such conferences,
discovery proceedings, hearings, trials or appeals as may reasonably be
requested by the Indemnifying Party. In the event that the Indemnifying Party
does not satisfy the Litigation Conditions or does not notify the Indemnified
Party of the Indemnifying Party’s intent to defend any Third Party Claim within
ten (10) Business Days after notice thereof, the Indemnified Party may (without
further notice to the Indemnifying Party) undertake the defense thereof with
counsel of its choice and at the Indemnifying Party’s expense (including
reasonable, out-of-pocket attorneys’ fees and costs and expenses of enforcement
or defense). The Indemnifying Party or the Indemnified Party, as the case may
be, shall have the right to join in (including the right to conduct discovery,
interview
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and examine witnesses, and participate in all settlement conferences), but not
control, at its own expense, the defense of any Third Party Claim that the other
Party is defending as provided in this Agreement.
10.4.3. Settlement. The Indemnifying Party shall not, without the prior written
consent of the Indemnified Party, enter into any compromise or settlement that
commits the Indemnified Party to take, or to forbear to take, any action. The
Indemnified Party shall have the sole and exclusive right to settle any Third
Party Claim, on such terms and conditions as it deems reasonably appropriate, to
the extent such Third Party Claim involves equitable or other non-monetary
relief, but shall not have the right to settle such Third Party Claim to the
extent such Third Party Claim involves monetary damages without the prior
written consent of the Indemnifying Party. Each of the Indemnifying Party and
the Indemnified Party shall not make any admission of liability in respect of
any Third Party Claim without the prior written consent of the other party, and
the Indemnified Party shall use reasonable efforts to mitigate Liabilities
arising from such Third Party Claim.
10.5. Insurance. Each Party further agrees to obtain and maintain, during the
Term, commercial general liability insurance, including products liability
insurance (or clinical trials insurance, whichever is applicable), with
reputable and financially secure insurance carriers (or pursuant to a program of
self-insurance reasonably satisfactory to the other Party) to cover its
indemnification obligations under Section 10.2 or Section 10.3, as applicable,
in each case with limits of not less than *** per occurrence and in the
aggregate. Insurance shall be procured with carriers having an A.M. Best Rating
of A-VII or better. All deductibles/retentions of the named insured shall be the
sole responsibility of the named insured. Products liability and/or clinical
trials coverage shall be maintained for *** following termination or expiration
of this Agreement.
11. MISCELLANEOUS.
11.1. HSR Filing. Each of OPKO and Pfizer will, by January 7, 2015 (or such
later time as may be agreed to in writing by the Parties) file with the United
States Federal Trade Commission and the Antitrust Division of the United States
Department of Justice any HSR Filing required of it under the HSR Act, and shall
request early termination in such filing. The Parties will cooperate with one
another to the extent necessary in the preparation of any such HSR Filing. Each
Party will be responsible for its own costs, expenses and filing fees associated
with any such HSR Filing; provided, however, that Pfizer will be solely
responsible for any fees (other than penalties that may be incurred as a result
of actions or omissions on the part of OPKO) required to be paid to any
Governmental Authority in connection with submitting any such HSR Filing.
Notwithstanding the foregoing, nothing in this Agreement shall obligate, or be
construed to obligate, Pfizer (i) to dispose, transfer or hold separate, or
cause any of its Affiliates to dispose, transfer or hold separate any assets or
operations, or to commit or to cause OPKO or any of its Affiliates to dispose of
any assets; (ii) to discontinue or cause any of its Affiliates to discontinue
offering any product or service, or to commit to cause OPKO or any of its
Affiliates to discontinue offering any product or service; or (iii) to make or
cause any of its Affiliates to make any commitment (to any Governmental
Authority or otherwise) regarding its future operations or the future operations
of OPKO or any of its Affiliates, and OPKO shall not agree, commit or consent to
any of such restrictions with respect to itself or any its Affiliates, or permit
any of its Affiliates to do so, in each case without the prior written consent
of Pfizer.
11.2. Termination upon HSR Denial. In the event that the Parties make an HSR
Filing under Section 11.1, this Agreement will terminate (a) at Pfizer’s
election, immediately upon
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notice to OPKO, in the event that the United States Federal Trade Commission or
the United States Department of Justice seeks a preliminary injunction under the
HSR Act against OPKO and Pfizer to enjoin the transactions contemplated by this
Agreement, or (b) at the election of either Party, immediately upon notice to
the other Party, in the event that the United States Federal Trade Commission or
the United States Department of Justice obtains a preliminary injunction under
the HSR Act against OPKO or Pfizer to enjoin the transactions contemplated by
this Agreement. Notwithstanding the foregoing, this Section 11.2 will not apply
in the event that Pfizer reasonably determines that an HSR Filing is not
required.
11.3. Other Government Approvals. Each of OPKO and Pfizer will cooperate with
the other Party and use such Party’s Commercially Reasonable Efforts to make all
registrations, filings and applications, to give all notices and to obtain as
soon as practicable all governmental or other consents, transfers, approvals,
orders, qualifications, authorizations, permits and waivers, if any, and to do
all other things necessary or desirable for the consummation of the transactions
as contemplated hereby.
11.4. Assignment. Neither this Agreement nor any interest hereunder shall be
assignable by a Party without the prior written consent of the other Party,
except as follows: (a) a Party may assign its rights and obligations under this
Agreement by way of a sale of itself or of the portion of its business to which
this Agreement relates, through a merger, sale of assets and/or sale of stock or
ownership interest provided that the assignee shall expressly agree to be bound
by such Party’s obligations under this Agreement and that such sale is not
primarily for the benefit of its creditors, or (b) such Party may assign its
rights and obligations under this Agreement to any of its Affiliates, provided
that the assignee shall expressly agree to be bound by such Party’s obligations
under this Agreement and that such Party shall remain liable for all of its
rights and obligations under this Agreement. In addition, either Party may
assign its rights and obligations under this Agreement to a Third Party where
such Party or its Affiliate is required, or makes a good faith determination
based on advice of counsel, to divest a Licensed Product in order to comply with
Applicable Law or the order of any Governmental Authority as a result of a
merger or acquisition, provided that the assignee shall expressly agree to be
bound by the Party’s obligations under this Agreement. Each Party shall promptly
notify the other Party of any assignment or transfer under the provisions of
this Section 11.4. This Agreement shall be binding upon the successors and
permitted assigns of the Parties and the name of a Party appearing herein shall
be deemed to include the names of such Party’s successors and permitted assigns
to the extent necessary to carry out the intent of this Agreement. Any
assignment not in accordance with this Section 11.4 shall be void.
11.5. Further Actions. Each Party shall duly execute and deliver, or cause to be
duly executed and delivered, such further instruments and do and cause to be
done such further ministerial, administrative, or similar acts and things,
including the filing of such assignments, agreements, documents and instruments,
as may be necessary or as the other Party may reasonably request in connection
with this Agreement or to carry out more effectively the provisions and purposes
hereof, or to better assure and confirm unto the other Party its rights and
remedies under this Agreement.
11.6. Performance. To the extent that the performance of a Party’s obligations
hereunder is adversely affected by the other Party’s failure to perform its
obligations hereunder, the impact of such performance failure will be taken into
account in determining whether such Party has used its requisite efforts (which
may be Commercially Reasonable Efforts) to perform any such affected obligations
as required by this Agreement.
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11.7. Force Majeure. Each Party shall be excused from liability and from the
performance of its obligations or the obligations of its Affiliates and/or
sublicensees under this Agreement to the extent that such performance is
prevented in whole or in part by Force Majeure and the non-performing Party
promptly provides written notice of such Force Majeure to the other Party. Such
excuse shall be continued so long as the condition constituting Force Majeure
continues and the non-performing Party takes Commercially Reasonable Efforts to
remove the condition. “Force Majeure” shall include conditions beyond the
control of the Party or its Affiliates and/or sublicensees, including an act of
God, voluntary or involuntary compliance with any regulation, Applicable Law or
order of any government, war, act of terror, civil commotion, labor strike or
lock-out, epidemic, failure or default of public utilities or common carriers,
destruction of production facilities or materials by fire, earthquake, or storm,
or like catastrophe. Each Party shall notify the other Party promptly in writing
following the occurrence or after becoming aware of the occurrence of any Force
Majeure, whereupon the Parties shall promptly co-operate so as to mitigate the
effects of such Force Majeure and the Party suffering the Force Majeure shall be
obliged to use reasonable efforts to overcome the circumstances thereof. In the
event a Party suspends its performance for a period of three (3) or more months
due to a Force Majeure, the Parties shall consult in good faith to develop and
implement a plan for mitigating the same.
11.8. Notices. Each communication and document made or delivered by one Party to
the other Party under this Agreement shall be made in the English language. All
notices, consents, approvals, request or other communications required hereunder
given by one Party to the other shall be in writing and made by (a) personal
delivery, (b) first class certified mail with return receipt requested or (c)
next-day delivery by major international courier with confirmation of delivery.
Notices will be deemed given either upon receipt or as of the date of certified
delivery by a reputable delivery service, whichever is earlier.
To Pfizer:
Chief Counsel, Global Innovative Pharma Business
Pfizer Inc.
235 East 42nd Street
New York, New York 10017-5755

with a copy to:
Vice President, GIP Global Medicines Development Group
Rare Disease Lead
Pfizer Inc.
400 Campus Drive
Collegeville, PA 19426
(484) 865-0226

To OPKO:
Steven D. Rubin
Executive Vice President
OPKO Health, Inc.
4400 Biscayne Boulevard
Miami, Florida 33137
(305) 575-6015
srubin@opko.com

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with a copy to:

Kate Inman
General Counsel
OPKO Health, Inc.
4400 Biscayne Blvd.
Miami, FL 33137
Office: 305.575.4138
kinman@opko.com

        and a copy to:

         Asher Rubin
         Hogan Lovells US LLP
100 International Drive, Suite 2000
Baltimore, MD 21202
Office: 410.659.2777
asher.rubin@hoganlovells.com

11.9. Amendment. No amendment, modification or supplement of any provision of
this Agreement shall be valid or effective unless made in writing and signed by
a duly authorized representative of each Party.

11.10. Waiver. No provision of this Agreement shall be waived by any act,
omission or knowledge of a Party or its agents or employees except by an
instrument in writing expressly waiving such provision and signed by a duly
authorized representative of the waiving Party. The waiver by either Party of
any breach of any provision by the other Party shall not be construed to be a
waiver of any succeeding breach of such provision or a waiver of the provision
itself.
11.11. Severability. If any clause or portion thereof in this Agreement is for
any reason held to be invalid, illegal or unenforceable, the same shall not
affect any other portion of this Agreement, as it is the intent of the Parties
that this Agreement be construed in such fashion as to maintain its existence,
validity and enforceability to the greatest extent possible. In any such event,
this Agreement shall be construed as if such clause or portion thereof had never
been contained in this Agreement, and there shall be deemed substituted therefor
such provision as will most nearly carry out the intent of the Parties as
expressed in this Agreement to the fullest extent permitted by Applicable Law.
11.12. Export Control. This Agreement is made subject to any restrictions
concerning the export of products or technical information from the United
States or other countries that may be imposed upon or related to OPKO or Pfizer
from time to time. Each Party agrees that it will not export, directly or
indirectly, any technical information acquired from the other Party under this
Agreement or any products using such technical information to a location or in a
manner that at the time of export requires an export license or other
governmental approval, without first obtaining the written consent to do so from
the appropriate agency or other governmental entity.
11.13. Dispute Resolution. Except as otherwise set forth in this Agreement, if
any dispute or disagreement arises between Pfizer and OPKO in respect of this
Agreement, they will follow the following procedures in an attempt to resolve
the dispute or disagreement:
11.13.1. The Party claiming that such a dispute exists will give notice in
writing (“Notice of Dispute”) to the other Party of the nature of the dispute.
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11.13.2. Within thirty (30) days of receipt of a Notice of Dispute, a
representative of each of the Parties who is at least a senior vice president
level or higher will meet at a mutually agreed-upon time and location (which may
include by teleconference) for the purpose of resolving such dispute.
11.13.3. If, within a further period of sixty (60) days, the dispute has not
been resolved, or if, for any reason, the meeting described in Section 11.13.2
has not been held within thirty (30) days of initial receipt of the Notice of
Dispute, then the Parties agree that (i) *** or if such dispute is not expressly
stated to be resolved through expedited arbitration in accordance with Section
11.14, ***, and (ii) *** or if such dispute is expressly stated to be resolved
through expedited arbitration in accordance with Section 11.14, then ***.
Notwithstanding any provision of this Agreement to the contrary, either Party
may immediately initiate litigation in any court of competent jurisdiction
seeking any remedy at law or in equity, including the issuance of a preliminary,
temporary or permanent injunction, to preserve or enforce its rights under this
Agreement. The provisions of this Section 11.13 shall survive for *** from the
date of termination or expiration of this Agreement.

11.14. Expedited Dispute Resolution. The following disputes will be finally
settled by binding arbitration in accordance with the procedures set forth on
Schedule 11.14: (a) any dispute relating to the existence of a Development
Limitation referred by a Party for expedited arbitration in accordance with
Section 11.13.3; and (b) any other dispute hereunder that a Party has the
express right to refer for resolution through expedited arbitration in
accordance with this Section 11.14.
11.15. Governing Law. This Agreement, and all claims arising under or in
connection therewith, shall be governed by and interpreted in accordance with
the substantive laws of the State of New York, without regard to conflict of law
principles thereof.
11.16. Jurisdiction. Each Party to this Agreement hereby (a) irrevocably submits
to the exclusive jurisdiction of the state courts of the State of New York or
the United States District Court for the Southern District of New York for the
purpose of any and all actions, suits or proceedings arising in whole or in part
out of, related to, based upon or in connection with this Agreement or the
subject matter hereof, (b) waives to the extent not prohibited by Applicable
Law, and agrees not to assert, by way of motion, as a defense or otherwise, in
any such action, any claim that it is not subject personally to the jurisdiction
of the above-named courts, that its property is exempt or immune from attachment
or execution, that any such action brought in one of the above-named courts
should be dismissed on grounds of forum non conveniens or should be transferred
to any court other than one of the above-named courts, or that this Agreement or
the subject matter hereof may not be enforced in or by such court and (c) agrees
not to commence any such action other than before one of the above-named courts
nor to make any motion or take any other action seeking or intending to cause
the transfer or removal of any such action to any court other than one of the
above-named courts, whether on the grounds of forum non conveniens or otherwise.
11.17. No Jury Trial. THE PARTIES EXPRESSLY WAIVE AND FOREGO ANY RIGHT TO TRIAL
BY JURY.
11.18. Entire Agreement. This Agreement, together with its Exhibits, sets forth
the entire agreement between the Parties as to its subject matter and supersedes
all proposals, oral or written, and all other prior communications between the
Parties with respect to such subject matter, including, without limitation, that
certain Confidential Disclosure Agreement by and
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between the Parties, dated *** (the “CDA”), which is hereby terminated as of the
Original Effective Date. The Parties acknowledge and agree that, as of the
Original Effective Date, all Confidential Information (as defined in the CDA)
disclosed by a Party pursuant to the CDA shall be considered Confidential
Information of such Party and subject to the terms set forth in this Agreement.
11.19. Independent Contractors. The Parties are independent contractors under
this Agreement. Nothing herein contained shall be deemed to create an
employment, agency, joint venture or partnership relationship between the
Parties hereto or any of their agents or employees, or any other legal
arrangement that would impose liability upon one Party for the act, or failure
to act, of the other Party. Neither Party shall have any express or implied
power to enter into any contracts or commitments or to incur any liabilities in
the name of, or on behalf of, the other Party, or to bind the other Party in any
respect whatsoever. The Parties acknowledge and agree that neither Party owes
the other any fiduciary or similar duties or obligations by virtue of the
relationship created by this Agreement. Without limiting the foregoing, the
Parties also acknowledge and agree that if a court of competent jurisdiction or
an arbitrator should determine that, notwithstanding the terms of this Section
11.19, such fiduciary or other obligations exist, the Parties hereby waive such
duties and obligations and agree not to assert or rely upon such duties or
obligations in connection with any dispute arising out of or relating to this
Agreement.
11.20. No Third Party Rights or Obligations. No provision of this Agreement
shall be deemed or construed in any way to result in the creation of any rights
or obligations in any Person not a Party to this Agreement. However, either
Party may decide, in its sole discretion, to use one or more of its Affiliates
to perform its obligations and duties hereunder, provided that such Party shall
remain liable hereunder for the performance by any such Affiliate(s) of any such
obligations.
11.21. Headings. The descriptive headings of this Agreement are included herein
for ease of reference only and shall be of no force or effect in construing or
interpreting any of the provisions of this Agreement.
11.22. Counterparts. This Agreement may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall
constitute one and the same document. Counterparts may be signed and delivered
by facsimile or PDF file, with the same effect as if delivered personally.
11.23. OPKO Parent Co. Guaranty. OPKO Health, Inc., a corporation formed under
the laws of Delaware with offices at 4400 Biscayne Blvd., Miami, Florida 33138,
and a parent company of OPKO (the “Guarantor”), (i) hereby unconditionally
guarantees the due and punctual payment and performance of all of OPKO’s
obligations and commitments under both (a) this Agreement, with respect to
OPKO’s obligations and commitments arising following the Amendment Effective
Date and (b) the Original Agreement, with respect to OPKO’s obligations and
commitments arising following the Original Execution Date but prior to the
Amendment Effective Date and (ii) without limiting the foregoing or being
limited thereby, hereby further covenants to procure and cause OPKO and its
Affiliates to take such actions that may be necessary or useful to support and
duly complete the performance of OPKO’s obligations and commitments under both
(a) this Agreement, with respect to OPKO’s obligations and commitments arising
following the Amendment Effective Date and (b) the Original Agreement, with
respect to OPKO’s obligations and commitments arising following the Original
Execution Date but prior to the Amendment Effective Date, with respect to each,
including in relation to Pfizer’s exercise of its rights under this Agreement
and the Original Agreement (collectively, (i) and (ii) the “Parent Guaranty”).
This Parent Guaranty is an irrevocable guaranty of payment
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and performance (and not just of collection) and shall continue in effect
notwithstanding any extension or modification of the terms of this Agreement,
any assumption of any such guaranteed obligations by any other party or any
other act or event that might otherwise operate as a legal or equitable
discharge of Guarantor. Guarantor hereby waives all its rights to subrogation
arising out of any payment or performance by Guarantor under this Parent
Guaranty. The obligations of Guarantor hereunder shall be absolute and
unconditional, and shall not be affected by or contingent upon (I) the
liquidation or dissolution of, or the merger or consolidation of OPKO with or
into any corporation, or any sale or transfer by OPKO or all or any part of its
or their property or assets, (II) the bankruptcy, receivership, insolvency,
reorganization or similar proceedings involving or affecting OPKO or (III) any
modification, alteration, amendment or addition of or to the Agreement.
Guarantor hereby waives all suretyship defenses and protest, notice of protest,
demand for performance, diligence, notice of any other action at any time taken
or omitted by Pfizer and, generally, all demands and notices of every kind in
connection with this Parent Guaranty, and OPKO’s obligations hereby guaranteed,
and which Guarantor may otherwise assert against Pfizer. This Parent Guaranty
shall continue to be effective or shall be reinstated, as the case may be, if at
any time payment or performance of any of the obligations of OPKO under this
Agreement is rescinded or must otherwise be restored or returned by Pfizer upon
the insolvency, bankruptcy or reorganization of OPKO or otherwise. Guarantor
acknowledges that each of the waivers set forth in this Parent Guaranty is made
with full knowledge of its significance and consequences and under the
circumstances the waivers are reasonable and not contrary to public policy. If
any of said waivers is determined to be contrary to any applicable law or public
policy, such waivers shall be effective only to the extent permitted by law.

[Signature page to follow]

83

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IN WITNESS WHEREOF, authorized representatives of the Parties have duly executed
this Agreement as of the Amendment Execution Date.

PFIZER INC.

By: /s/ Suneet Varma
Name: Suneet Varma
Title: Global President, RD BU
OPKO IRELAND LTD.

By: /s/ J. Gaul
Name: J. Gaul
Title: Director

As a party to this Agreement solely with respect to  the provisions of Section
11.23:

OPKO HEALTH, INC.

By: /s/ Steven D. Rubin 
Name: Steven D. Rubin
Title: Executive Vice President - Administration

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Schedule 1.36 – Compounds
Schedule 1.56 – ***
Schedule 1.70 – Genotropin Products
Schedule 1.86 – ***
Schedule 1.98 – Licensed Patent Rights
Schedule 1.190 – ***
Schedule 3.10.3(b) – ***
Schedule 5.4 – Example Profit Share Calculation
Schedule 8.3 – OPKO Disclosure Schedule
Schedule 11.14 – Expedited Dispute Resolution

Exhibit A Development Plan
Exhibit B Development Budget
Exhibit C Press Release

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Schedule 1.36 – Compounds
***

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Schedule 1.56 – ***
Each of the following countries:
***

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Schedule 1.70 - Genotropin Products

The Genotropin products sold by Pfizer and its Affiliates under various
trademarks in various jurisdictions worldwide:

***

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Schedule 1.86 – ***
Each of the following countries:
 ***

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Schedule 1.98 - Licensed Patent Rights

(a) - Licensed hGH-Specific Patents

U.S. Patents and Applications

***

Patents and Applications Outside of U.S.

***

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(b) - Licensed OPKO Core Patents

U.S. Patents and Applications

***

Patents and Applications Outside of U.S.

***

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Schedule 1.190 – ***
***

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Schedule 3.10.3(b) – Additional Pediatric Indications
***

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Schedule 5.4 – Example Profit Share Calculation

***

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Schedule 8.3 – OPKO Disclosure Schedule

***

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Schedule 11.14 – Expedited Dispute Resolution
Any dispute that is referred to resolution in accordance with the procedures set
forth in this Schedule 11.14 will be submitted to fast-track, binding
arbitration in accordance with the following terms:
1. Arbitration will be conducted in New York, New York under the rules of the
American Arbitration Association (the “AAA”) in effect at the time of submission
for the resolution of commercial disputes in the most expedited manner permitted
by such rules. The Parties will mutually select, within ten (10) days of a
dispute being referred to arbitration as set forth herein, a single arbitrator
to resolve such dispute. If the Parties, acting in good faith, are unable to
agree on an arbitrator during such ten (10) day period, then the Parties will
promptly request that the AAA select the arbitrator within ten (10) days
following the Parties making such a request of the AAA. The arbitrator will be a
professional in business or licensing *** (ii) *** with applicable Regulatory
Authorities and (iii) ***. Additionally, the arbitrator shall not be or have
been an employee, consultant, officer, director or stockholder of either Party
or any Affiliate of either Party and not have a conflict of interest under any
applicable rules of ethics. The cost of the arbitration will be borne equally by
the Parties. Except in a proceeding to enforce the results of the arbitration or
as otherwise required by Applicable Law, neither Party nor any arbitrator may
disclose (a) the existence, content or results of any arbitration hereunder, (b)
the content of any Brief submitted by a Party pursuant to Paragraph 2 hereof or
(c) the content of any response to a Brief submitted by a Party pursuant to
Paragraph 3 hereof, with respect to (a)-(c), without the prior written agreement
of each Party.

2. *** after such matter is referred to arbitration (provided that, if an
arbitrator has not been selected within such *** period, then within ***
following the selection of an arbitrator), each Party will provide the
arbitrator with a proposal and written memorandum in support of its position
regarding the dispute at issue, as well as any documentary evidence it wishes to
provide in support thereof (each a “Brief”), and the arbitrator will provide
each Party’s Brief to the other Party after it receives it from both Parties.

3. Within *** after a Party submits its Brief to the arbitrator as set forth in
Paragraph 2 hereof, the other Party will have the right to respond thereto. The
response and any material in support thereof will be provided to the arbitrator
and the other Party.

4. The arbitrator will have the right to meet with the Parties as necessary to
inform the arbitrator’s determination and to perform independent research and
analysis. Within *** of the receipt by the arbitrator of both Parties’ responses
(or expiration of the *** period

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if any Party fails to submit a response), the arbitrator will *** in writing;
provided that ***.

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Exhibit A – Development Plan

[See attached.]

***

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Exhibit B – Development Budget

[See attached.]

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Exhibit C – Press Release

OPKO and Pfizer Enter into Global Agreement for
OPKO’s Long-Acting Human Growth Hormone (hGH-CTP)

•[hGH-CTP in global clinical development for the treatment of pediatric and
adult growth hormone deficiency (GHD)
•hGH-CTP has potential to reduce dosing frequency of human growth hormone to
single weekly injection from current standard of daily injection
•OPKO to receive upfront payment of $295 million and eligible to receive up to
an additional $275 million upon achievement of regulatory milestones
•Pfizer to obtain exclusive license to commercialize hGH-CTP globally

Miami, FL, and New York, NY, December [XX] - OPKO Health, Inc. (NYSE:OPK) and
Pfizer Inc. (NYSE: PFE) announced today that they have entered into a worldwide
agreement for the development and commercialization of OPKO’s long-acting
hGH-CTP for the treatment of growth hormone deficiency (GHD) in adults and
children, as well as for the treatment of growth failure in children born small
for gestational age (SGA) who fail to show catch-up growth by 2 years of age.
hGH-CTP has the potential to reduce the required dosing frequency of human
growth hormone to a single weekly injection from the current standard of one
injection per day. hGH-CTP is currently in a global phase 3 trial in adults and
a global phase 2 trial in children and has orphan drug designation in the U.S.
and Europe for both adults and children with GHD.

Under the terms of the agreement, OPKO will receive upfront payment of $295
million and is eligible to receive up to an additional $275 million upon the
achievement of certain regulatory milestones. Pfizer will receive the exclusive
license to commercialize hGH-CTP worldwide.

In addition, OPKO is eligible to receive initial royalty payments associated
with the commercialization of hGH-CTP for Adult GHD which is subject to
regulatory approval. Upon the launch of hGH-CTP for Pediatric GHD, which is
subject to regulatory approval, the royalties will transition to gross profit
sharing for both hGH-CTP and Pfizer’s Genotropin.

OPKO will lead the clinical activities and will be responsible for funding the
development programs for the key indications, which includes Adult and Pediatric
GHD and Pediatric SGA. Pfizer will be responsible for all development costs for
additional indications as well as all post-marketing studies. In addition,
Pfizer will fund the commercialization activities for all indications and lead
the manufacturing activities covered by the global development plan.

"We believe this collaboration will help advance our commitments to patients
with Adult and Pediatric Growth Hormone Deficiency as we believe Pfizer’s
strengths, expertise and presence in the

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human growth hormone space makes them the ideal partner for our hGH-CTP program.
Our collaboration enables full alignment between Pfizer and OPKO to optimize
development and potentially bring an innovative treatment to patients. We
believe that the global growth hormone market is currently valued at more than
$3 billion, and believe that hGH-CTP has the potential to be the best in class
long-acting growth hormone product. Our long acting human growth hormone is our
most advanced product candidate utilizing our CTP technology to extend the half
life of a broad range of therapeutic peptides and proteins. By reducing the
number of injections, our technology can improve patient compliance,” said
OPKO's CEO, Phillip Frost, M.D.

“This agreement strengthens Pfizer’s commitment to rare diseases, and we are
pleased to work with OPKO to help provide a potential next-generation therapy
for patients with Adult and Pediatric Growth Hormone Deficiency,” said Geno
Germano, Group President, Pfizer Global Innovative Pharma (GIP). “Long-acting
growth hormone is the first innovation in the GHD space in 20 years. hGH-CTP
would be complementary to our existing Genotropin franchise, and could
potentially provide an option that could improve patients’ adherence to
treatment with once weekly dosing.”
The transaction is subject to customary Hart-Scott-Rodino approval and is
expected to close during the first-quarter 2015.

About hGH-CTP
hGH-CTP is a novel, long-acting recombinant human growth hormone analog being
developed by OPKO for the treatment of children with growth failure due to
inadequate endogenous growth hormone secretion, and adults with growth hormone
deficiency (GHD) of either childhood or adult-onset etiology. hGH-CTP is
intended to reduce the burden of daily injection therapy by requiring only
weekly injections potentially improving compliance and treatment outcomes.
OPKO’s proprietary technology allows the company to extend the hormone’s
half-life without the use of polymers, encapsulation techniques, or
nanoparticles. This technology is based on a natural peptide, the C-terminal
peptide (CTP) of the beta chain of human chorionic gonadotropin (hCG). OPKO has
an ongoing pivotal Phase 3 clinical trial in adults for hGH-CTP and a Phase 2
clinical trial in pediatric patients. hGH-CTP has been granted orphan drug
designation in the U.S. and Europe for both adults and children with growth
hormone deficiency.

About OPKO Health
OPKO is a multinational biopharmaceutical and diagnostics company that seeks to
establish industry-leading positions in large, rapidly growing markets by
leveraging its discovery, development and commercialization expertise and novel
and proprietary technologies. For more information, visit http://www.OPKO.com.

Pfizer and Rare Diseases

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Rare diseases are among the most serious of all illnesses and impact millions of
patients worldwide, representing an opportunity to apply our knowledge and
expertise to help make a significant impact in addressing unmet medical needs.
The Pfizer focus on rare diseases builds on more than a decade of experience and
a global portfolio of 22 medicines approved worldwide that treat rare diseases
in the areas of hematology, neuroscience, inherited metabolic disorders,
pulmonology, and oncology.
About Pfizer Inc.
At Pfizer, we apply science and our global resources to bring therapies to
people that extend and significantly improve their lives. We strive to set the
standard for quality, safety and value in the discovery, development and
manufacture of health care products. Our global portfolio includes medicines and
vaccines as well as many of the world's best-known consumer health care
products. Every day, Pfizer colleagues work across developed and emerging
markets to advance wellness, prevention, treatments and cures that challenge the
most feared diseases of our time. Consistent with our responsibility as one of
the world's premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and expand
access to reliable, affordable health care around the world. For more than 150
years, Pfizer has worked to make a difference for all who rely on us. To learn
more, please visit us at www.pfizer.com.

SAFE HARBOR STATEMENT

[This press release contains "forward-looking statements," as that term is
defined under the Private Securities Litigation Reform Act of 1995 (PSLRA),
which statements may be identified by words such as "expects," "plans,"
"projects," "will," "may," "anticipates," "believes," "should," "intends,"
"estimates," and other words of similar meaning, including statements regarding
expected benefits of hGH-CTP), whether the collaboration with Pfizer will be
successful, whether OPKO's clinical trials for adult and pediatric growth
hormone deficiency will support marketing approval, whether hGH-CTP will be
successfully developed or commercialized, expectations regarding the product,
its efficacy, safety and market potential, as well as other non-historical
statements about our expectations, beliefs or intentions regarding our business,
technologies and products, financial condition, strategies or prospects. Many
factors could cause our actual activities or results to differ materially from
the activities and results anticipated in forward-looking statements. These
factors include those described in our filings with the Securities and Exchange
Commission, as well as the risks inherent in funding, developing and obtaining
regulatory approvals of new, commercially-viable and competitive products and
treatments. In addition, forward-looking statements may also be adversely
affected by general market factors, competitive product development, product
availability, federal and state regulations and legislation, the regulatory
process for new products and indications, manufacturing issues that may arise,
patent positions and litigation, among other factors. The forward-looking
statements contained in this press release speak only as of the date the
statements were made, and we do not undertake any obligation to update
forward-looking statements. We intend that all forward-looking statements be
subject to the safe-harbor provisions of the PSLRA.]

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PFIZER DISCLOSURE NOTICE: The information contained in this release is as of
December [ ], 2014. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new information or future
events or developments.
This release contains forward-looking information about an agreement between
Pfizer and OPKO for the development and commercialization of hGH-CTP that
involves substantial risks and uncertainties that could cause actual results to
differ materially from those expressed or implied by such statements.
Forward-looking statements include, among other things, those regarding hGH-CTP
and the collaboration, including their potential benefits and market potential,
as well as those about the anticipated timing of the closing of the transaction.
Risks and uncertainties include, among other things, the uncertainties inherent
in research and development, including the ability to meet anticipated clinical
study commencement and completion dates as well as the possibility of
unfavorable study results; whether and when biologics license applications may
be filed in any jurisdictions for hGH-CTP for any indication; whether and when
any such applications may be approved by regulatory authorities, which will
depend on the assessment by such regulatory authorities of the benefit-risk
profile suggested by the totality of the efficacy and safety information
submitted; decisions by regulatory authorities regarding labeling and other
matters that could affect the availability or commercial potential of hGH-CTP in
any such indications; risks relating to the satisfaction of conditions to
closing the transaction in the anticipated timeframe or at all; and competitive
developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual
Report on Form 10-K for the fiscal year ended December 31, 2013 and in its
subsequent reports on Form 10-Q, including in the sections thereof captioned
“Risk Factors” and “Forward-Looking Information That May Affect Future Results”,
as well as in its subsequent reports on Form 8-K, all of which are filed with
the SEC and available at www.sec.gov and www.pfizer.com.

Contact: ]