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separately with the Commission.

DEVELOPMENT AND COMMERCIALIZATION LICENSE AGREEMENT
This Development and Commercialization License Agreement (the “Agreement”) is
entered into as of December 13, 2014 (the “Execution 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 owns or otherwise Controls (as defined below) the Licensed
Technology (as defined below) and desires to grant an exclusive license to
Pfizer in the Territory (as defined below); and
WHEREAS, Pfizer has extensive experience and expertise in the development and
commercialization of pharmaceutical products and desires to acquire such an
exclusive license in the Territory to the Licensed Technology;
NOW, THEREFORE, in consideration of the mutual covenants and agreements provided
herein, the Parties hereby agree as follows:
1.
DEFINITIONS.

1.1.    “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.
1.2.    “Additional Activities” means proposed activities outside the scope of
the then current Development Plan, including any new Trials for new indications.
1.3.    “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 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

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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.
1.4.    “AGHD,” or “Adult Growth Hormone Deficiency” means growth hormone
deficiency in adult patients, whether as a result of adult onset or childhood
onset causes.
1.5.    “Agreement” has the meaning set forth in the Preamble.
1.6.     “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.
1.7.    “Approved CRO” has the meaning set forth in Section 3.1.6(a).
1.8.    “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.
1.9.    “Approved Vendor” has the meaning set forth in Section 3.1.6(b).
1.10.    “Audited Party” has the meaning set forth in Section 5.7.2.
1.11.    “Auditing Party” has the meaning set forth in Section 5.7.2.
1.12.    “Auditing Plan” has the meaning set forth in Section 4.7.1.
1.13.    “Bankruptcy Code” has the meaning set forth in Section 9.4.1.
1.14.    “Bankruptcy Event” has the meaning set forth in Section 9.4.1.
1.15.    “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.
1.16.    “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
achieved analogous

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regulatory approval based upon reference to a Licensed Product from another
applicable Regulatory Authority.
1.17.    “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.
1.18.    “Business Day” means a day other than a Saturday, Sunday or bank or
other public holiday in New York, New York.
1.19.    “Calendar Quarter” means the respective periods of three consecutive
calendar months ending on March 31, June 30, September 30 and December 31.
1.20.    “CDA” has the meaning set forth in Section 11.17.
1.21.    “Chairperson” has the meaning set forth in Section 3.2.2.
1.22.    “Clinical Data Package” has the meaning set forth in Section 3.4.2.
1.23.    “Clinical Datasets” has the meaning set forth in Section 3.4.3(a).
1.24.    “Clinical Trial Agreement” has the meaning set forth in Section
4.2.1(b).
1.25.    “Clinical Investigator” means the principal investigator at each Site.
1.26.    “Clinical Investigator Meeting” has the meaning set forth in Section
4.2.2.
1.27.    “Clinical Trial Registries” has the meaning set forth in
Section 3.3.4(a).
1.28.     “CMC Information” means the chemistry, manufacturing and control
information required for the submission of a BLA.
1.29.    “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.
1.30.    “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

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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; ***.
1.31.    “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.
1.32.    “Compound” means any human growth hormone (hGH) polypeptide ***.
1.33.    “Confidential Information” has the meaning set forth in Section 7.1.
1.34.    “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.
1.35.    “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 ***).
1.36.    “CRO” means a contract research organization.
1.37.    “CRO Agreement” has the meaning set forth in Section 3.1.6(a).
1.38.    “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.

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1.39.    “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.
1.40.     “Data Management Plan” has the meaning set forth in Section 4.5.2.
1.41.    “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.
1.42.    “Development Budget” has the meaning set forth in Section 3.1.2(a).
1.43.    “Development Budget Cap” has the meaning set forth in Section 3.1.2(a).
1.44.    “Development Plan” has the meaning set forth in Section 3.1.1.
1.45.    “Device” means a proprietary delivery system for subcutaneous delivery
of any Compound.
1.46.    “DG44 Materials” has the meaning set forth in Section 8.4.7.
1.47.    “Diligence Issue” has the meaning set forth in Section 3.10.2.
1.48.    “Disclosed Third Party Agreement” has the meaning set forth in Section
8.3.10.
1.49.    “Disclosing Party” has the meaning set forth in Section 7.2.
1.50.    “Effective Date” means the date upon which any required waiting period
under the HSR Act shall have expired or been terminated.
1.51.    “EMA” means the European Medicines Agency and any successor agency or
authority thereto.
1.52.    “End of Phase II Meetings” means each of (i) the end of the phase II
meeting as described in 21 C.F.R. § 312.47(b), (ii) the EMA CHMP Scientific
Advice/Protocol Assistance meeting and (iii) the equivalent scientific advice
meeting in 2015 with the PMDA.
1.53.    *** means the *** as of the Effective Date and to the extent not
included in the ***.
1.54.    *** 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 ***.

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1.55.    “EU Regulatory Approval” means the first approval of an MAA for a
Licensed Product in the EU.
1.56.    “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 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.
1.57.    “Execution Date” has the meaning set forth in the Preamble.
1.58.    “Existing Trials” has the meaning set forth in Section 3.12.
1.59.    “Expert Arbitrator” has the meaning set forth in Section 3.1.3(e).
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 Pricing
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.    “Governmental Authority” means any court, agency, department, authority
or other instrumentality of any national, state, county, city or other political
subdivision.
1.73.    “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.
1.74.    “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

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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.
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.    “IRB” means institutional review board.
1.85.    *** means the ***
1.86.    *** means that period beginning on the *** and ending on termination of
this Agreement in its entirety or termination of this Agreement for the ***
1.87.    “Japan Regulatory Approval” means the first approval by a PMDA for a
Licensed Product in Japan.
1.88.    “JDC” has the meaning set forth in Section 3.2.1.
1.89.    “Joint Developed IP” has the meaning set forth in Section 6.1.2(c).
1.90.    “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.

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1.91.    “Liability” has the meaning set forth in Section 10.2.
1.92.    “Licensed Activities” has the meaning set forth in Section 6.5.1.
1.93.    “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 ***. The Licensed hGH-Specific Patents
are set forth on Schedule 1.96(a), as it may be updated by OPKO from time to
time.  
1.94.    “Licensed Know-How” means any Know-How that (a) is Controlled by OPKO
or any of its Affiliates as of the 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.
1.95.    “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 ***. Licensed OPKO Core
Patents are set forth on Schedule 1.96(b) as it may be updated by OPKO from time
to time.
1.96.    “Licensed Patent Rights” means any Patent Right that (a) is owned by
OPKO as of the Effective Date (including the Patent Rights listed in Schedule
1.96) 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 ***.
1.97.    “Licensed Product” means any pharmaceutical product containing one or
more Compounds. The Licensed Product may be used with or accompanied by a
Device.
1.98.    “Licensed Technology” means Licensed Patent Rights and Licensed
Know-How.
1.99.    “Litigation Conditions” has the meaning set forth in Section 10.4.2.
1.100.    “MAA” means Marketing Authorization Application.
1.101.    “Major EU Country” means any of France, Germany, Italy, Spain or the
United Kingdom.
1.102.    “Major Market Country” means any of ***.

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1.103.    “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.
1.104.    “Manufacturing Cost” means, ***.
1.105.     “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.
1.106.    “Medical Device Directive” means the directive 93/42/EEC, as amended
from time to time.
1.107.    “Monitoring Plan” has the meaning set forth in Section 4.8.
1.108.    “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 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.

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1.109.    “New Trials” has the meaning set forth in Section 3.13.
1.110.    “Non-Prevailing Party” has the meaning set forth in Section 3.1.3(e).
1.111.    “Notice of Dispute” has the meaning set forth in Section 11.13.1.
1.112.    “OPKO” has the meaning set forth in the Preamble.
1.113.    “OPKO Developed IP” has the meaning set forth in Section 6.1.2(b).
1.114.    “OPKO Indemnified Party” has the meaning set forth in Section 10.2.
1.115.    “OPKO Prosecuted IP” has the meaning set forth in Section 6.3.1(a).
1.116.    “OPKO Review Period” has the meaning set forth in Section 7.8.1.
1.117.    “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.
1.118.    “Party” and “Parties” have the meaning set forth in the Preamble.
1.119.    “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.
1.120.    “Partial Termination” has the meaning set forth in Section 9.5.2.
1.121.    “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.
1.122.    “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.

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1.123.     “Pfizer” has the meaning set forth in the Preamble.
1.124.    “Pfizer Developed CTP IP” has the meaning set forth in Section 2.4.
1.125.    “Pfizer Developed IP” has the meaning set forth in Section 6.1.2(a).
1.126.    “Pfizer Indemnified Party” has the meaning set forth in Section 10.3.
1.127.    “Pfizer Prosecuted IP” has the meaning set forth in Section 6.3.2(a).
1.128.    “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.
1.129.    “Pfizer Review Period” has the meaning set forth in Section 7.8.2.
1.130.    “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.
1.131.    “PGHD,” or “Pediatric Growth Hormone Deficiency” means growth failure
in pediatric patients due to an inadequate secretion of endogenous growth
hormone.
1.132.    “Pharmacovigilance Agreement” has the meaning set forth in Section
3.14.1.
1.133.    “PMDA” means the Pharmaceuticals and Medical Devices Agency, Japan and
any successor agency or authority thereto.
1.134.    “Prevailing Party” has the meaning set forth in Section 3.1.3(e).
1.135.    “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 ***.
1.136.    “Primary Indication” means AGHD, PGHD and PSGA.
1.137.    “Primary Regulatory Approval Goals” means the timely and efficient
achievement of those approvals set forth as Regulatory Milestones in Section
5.2.
1.138.    “Profit Share Term” means one or more of the *** as the context may
require.

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1.139.    “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.
1.140.    “Quality Agreement” has the meaning set forth in Section 3.6.2.
1.141.    “Receiving Party” has the meaning set forth in Section 7.2.
1.142.    “***” ***.
1.143.    “Regulatory Amendments” has the meaning set forth in
Section 3.1.3(b)(i).
1.144.    “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.
1.145.    “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.
1.146.    “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, ***, or jurisdiction in the Territory, other than
a Patent Right, including orphan drug 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.
1.147.    “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.
1.148.    “Regulatory Milestone” has the meaning set forth in Section 5.2.
1.149.    “Regulatory Milestone Payment” has the meaning set forth in Section
5.2.
1.150.    “Relevant Factors” means all relevant factors that may affect the
Development, Regulatory Approval or Commercialization of a Compound or Licensed
Product, ***

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1.151.    “***” ***.
1.152.    “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.
1.153.    “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.
1.154.    “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, ***. 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.
1.155.    “Safety Stock” has the meaning set forth in Section 3.8.3.
1.156.    “Site” has the meaning set forth in Section 4.2.1(b).
1.157.    “SOPs” has the meaning set forth in Section 4.1.
1.158.    “Specimens” has the meaning set forth in Section 4.6.
1.159.    “Statistical Analysis Plan” has the meaning set forth in Section
4.5.6.
1.160.    “Subject” has the meaning set forth in Section 4.3.2.
1.161.    “Subject Recruitment Plan” has the meaning set forth in Section 4.3.1.
1.162.    “Supply Agreement” has the meaning set forth in Section 3.6.2.

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1.163.    “Term” has the meaning set forth in Section 9.1.
1.164.    “***” has the meaning set forth in Section 9.5.2.
1.165.    “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 ***).
1.166.    “Third Party” means any Person other than Pfizer, OPKO or their
respective Affiliates.
1.167.    “Third Party Claim” has the meaning set forth in Section 10.4.1.
1.168.    “Third Party Infringement” has the meaning set forth in Section 6.4.1.
1.169.    “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.
1.170.    “Transition Plan” has the meaning set forth in Section 2.8.1.
1.171.    “Treaty” has the meaning set forth in Section 5.6.1.
1.172.    “Trial” means all clinical trials, including methodology and
non-interventional trials, whether initiated prior to or following the Execution
Date, to be conducted pursuant to the Development Plan.
1.173.    “Trial Database” has the meaning set forth in Section 4.5.3.
1.174.    “Trial Master File” has the meaning set forth in Section 4.5.4.
1.175.    “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.
1.176.    “Upfront Payment” has the meaning set forth in Section 5.1.
1.177.    “***” means the *** comprised of the ***.
1.178.    “***” means that period beginning on the ***and ending on termination
of this Agreement in its entirety ***.

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1.179.    “U.S. Regulatory Approval” means the first achievement of Regulatory
Approval of a BLA for a Licensed Product for an Approved Indication.
1.180.    “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 *** 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 *** 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.
1.181.    “VAT” has the meaning set forth in Section 5.6.1.
1.182.    “Vendor” means any Third Party with whom a Party may contract for the
procurement of services, equipment, tools, materials and/or supplies.
1.183.    “Vendor Agreement” has the meaning set forth in Section 3.1.6(b).
1.184.    “Vendor Oversight Plan” has the meaning set forth in Section 4.8.
1.185.    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,

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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 Effective Date, OPKO hereby
grants to Pfizer an 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 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 Product in the Territory,
solely to the extent necessary for performance by OPKO of its obligations
pursuant to Section 2.8 and Article 3 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 ***
(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, as
contemplated in Sections 2.3.1(a) or 2.3.1(b) above, 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.

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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 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.
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, 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.
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.

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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, estoppels 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 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 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 Effective Date, OPKO shall have ***
such Licensed 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.

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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. The Development of the Licensed Product shall be
governed by a plan setting forth the proposed overall program of Development of
Licensed Product and the respective Development responsibilities of the Parties
with respect to such program (the “Development Plan”), as it may be amended from
time to time in accordance with Section 3.1.2. The initial Development Plan is
attached hereto as Exhibit A. The Parties acknowledge and agree that, as further
set forth in the Development Plan, OPKO will be primarily responsible for and
shall make all day-to-day decisions regarding the conduct of clinical and
associated regulatory activities as specified in the Development Plan, subject
to oversight by the JDC. Pfizer will be primarily responsible for and shall make
all day-to-day decisions regarding the conduct of CMC activities and the conduct
of all other regulatory activities (other than those in respect of OPKO’s
clinical activities), including preparation of BLA regulatory submissions and
oversight of regulatory activities, as specified in the Development Plan subject
to oversight by the JDC. To the extent any terms or conditions of the
Development Plan expressly conflict with the terms or conditions of this
Agreement, the terms and provisions of this Agreement shall control.
3.1.2.    Development Budget; Allocation of Costs and Expenses.
(a)    The budget in respect of the cost to be incurred in connection with the
implementation of the Development Plan (the “Development Budget”) is attached
hereto as Exhibit B. The allocation of costs and expenses as between Pfizer and
OPKO will be as set forth in the Development Budget; provided, however, that
once OPKO has paid, or committed to pay, as its share of the Development Budget,
the aggregate sum of *** (the “Development Budget Cap”), all subsequent costs
and expenses incurred in connection with the implementation of the Development
Plan shall be allocated pursuant to the provisions of Section 3.1.3.
Notwithstanding the allocation of costs and expenses set forth in the
Development Budget, in the event there is a difference between the budgeted
amount for ***.
(b)     In the event the JDC determines that there is overlap and duplication of
efforts by Pfizer and OPKO with regard to *** under the Development Plan, the
JDC may, in its discretion, reduce the Development Budget Cap.

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(c)    Development Budget changes for Regulatory Amendments and Additional
Activities are set forth in Section 3.1.3(b).
(d)    All other amendments or modifications of the Development Budget,
including in connection with changes made to the Development Plan in accordance
with Section 3.1.3(c), shall be approved by the JDC subject to the Development
Budget Cap and the apportionment set forth in Section 3.1.2(a).
(e)    No later than *** days after the end of the Calendar Quarter during which
a Party has performed any Development activity in such Calendar Quarter pursuant
to the Development Plan, such Party shall submit to the other Party an invoice
setting forth the portion of such amount for which the other Party is
responsible for payment pursuant to the Development Plan, as such may be amended
from time to time. Each invoice shall be accompanied with reasonable supporting
explanation for such invoiced amounts.  The other Party (i.e., the Party not
performing such Development activity) shall pay such amount invoiced within ***
days of the end of the Calendar Quarter.  If both Parties will perform
Development activities in such Calendar Quarter pursuant to the Development
Plan, the Parties shall consolidate the payments for such Calendar Quarter into
a single payment from one Party to the other Party, so that the Parties are each
paying the amounts for which they are responsible pursuant to the Development
Budget. Any adjustments with respect to any previously submitted invoice by a
Party shall be reflected in the next such invoice delivered by such Party to the
other Party, such adjustments to be made in a manner consistent with the
internal accounting policies of such 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 Development activity in comparison to the related budget for such
Development activity as set forth in the Development Plan.
3.1.3.    Changes to the Development Plan.
(a)    Changes to the Development Plan. During the Term, any changes to the
Development Plan, including any country-specific appendices required by
Applicable Law and 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, will be prepared by OPKO with respect to the
clinical activities in the Development Plan and Pfizer with respect to the CMC
and regulatory activities in the Development Plan, or an Approved CRO or
Approved Vendor, and, except as otherwise set forth in this Article 3, will
require the JDC’s approval, to the

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extent responsibility is not already allocated to the Parties under the
Development Plan.
(b)    Development Plan: Regulatory Amendments.
(i)    During the Term, if either Party reasonably concludes that the
Development Plan requires amendment to comply with (x) any change in Applicable
Laws, (y) specific requirements imposed by, or recommendations of any,
Regulatory Authorities as a result of the End of Phase II Meetings and necessary
to obtain Regulatory Approval for a Licensed Product in one or more of the
Primary Indications, or (z) specific requirements imposed by Regulatory
Authorities other than those in (y) above (any such required amendments
described in (x), (y) or (z), “Regulatory Amendments”), the Parties shall
negotiate in good faith to reach resolution regarding appropriate written
amendments to the Development Plan and the Development Budget which will set
forth any additional or alternative Development activities as may be necessary
to implement such Regulatory Amendments. If the Parties are able to reach
agreement on such Regulatory Amendments to the Development Plan and the
Development Budget, *** in the case of amendments required pursuant to
subsection ***, and by *** in the case of amendments required pursuant to
subjection *** above. In the event that the Parties cannot so agree on
appropriate amendments to the Development Plan and the Development Budget,
within *** days following such time as the Parties began such negotiations (or
were obligated to enter into such negotiations), either Party shall have the
right to submit the matter for resolution in accordance with the arbitration
procedure set forth in Section 3.1.3(e) below.
(ii)    If Pfizer is the Prevailing Party following resolution of such matter
pursuant to such arbitration procedure, then (x) those amendments and
supplements to the Development Plan and the Development Budget that were
submitted to the Expert Arbitrator by Pfizer shall automatically be deemed to
amend and supplement the Development Plan and the Development Budget, and (y)
all additional costs and expenses associated with the Development activities
contemplated by such amendments and supplements shall be borne by the Party or
the Parties as set forth herein.
(iii)    If OPKO is the Prevailing Party following resolution of such matter
pursuant to such arbitration procedure, then (x) those amendments and
supplements to the Development Plan and the Development Budget that

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were submitted to the Expert Arbitrator by OPKO shall automatically be deemed to
amend and supplement the Development Plan and the Development Budget, and (y)
all additional costs and expenses associated with Development activities
contemplated by such amendments and supplements shall be borne by the Party or
the Parties as set forth herein. In addition, *** shall have the right, in its
sole discretion, to submit additional amendments and supplements to the
Development Plan and the Development Budget with respect to Development
activities that were contemplated in the proposal submitted to the Expert
Arbitrator by ***, which additional amendments and supplements shall
automatically be deemed to amend and supplement the Development Plan and the
Development Budget; provided, that (i) any additional costs and expenses
associated with such Development activities shall be borne by *** and (ii) ***
shall use Commercially Reasonable Efforts to ensure that the additional
activities related to such amendments and supplements do not unnecessarily
extend the timeline or cost required to achieve the Primary Regulatory Approval
Goals.
(c)    Development Plan: Additional Activities Within Development Plan.
(i)    During the Term, if (x) either Party reasonably concludes that additional
Development activities are reasonably necessary in connection with the
implementation of the Development Plan, and such activities are within the scope
of the Development Plan, or (y) the costs and expenses set forth in the
Development Budget are insufficient to allow for a proper implementation of the
activities and goals set forth in the Development Plan, the Parties shall
negotiate in good faith to reach resolution regarding appropriate amendments to
the Development Plan and the Development Budget which will address such
additional Development activities or Development Budget shortfall, as the case
may be. If the Parties are able to reach written agreement on such amendments to
the Development Plan and the Development Budget, all additional costs in respect
thereof shall be ***. In the event that the Parties cannot agree on appropriate
amendments to the Development Plan and the Development Budget, within *** days
following such time as the Parties began such negotiations (or were obligated to
enter into such negotiations), either Party shall have the right to submit the
matter for resolution in accordance with the arbitration procedure set forth in
Section 3.1.3(e) below. Following resolution of any matter so submitted for
resolution in accordance with such arbitration procedures, (x) those amendments
and supplements to the Development Plan and the Development Budget that were
submitted to the Expert Arbitrator by the Prevailing Party

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shall automatically be deemed to amend and supplement the Development Plan and
the Development Budget, and (y) all additional costs and expenses associated
with the Development activities contemplated by such amendments and supplements
*** by the Parties.
(ii)    In addition, *** shall have the right, in its sole discretion, to submit
additional amendments and supplements to the Development Plan and the
Development Budget which reflect any proposed amendments or supplements that
were made by either Party pursuant to clause (i) above, which additional
amendments and supplements shall automatically be deemed to amend and supplement
the Development Plan and the Development Budget; provided, that (i) any
additional costs and expenses associated with such Development activities shall
be borne by *** and (ii) *** shall use Commercially Reasonable Efforts to ensure
that the additional activities related to such amendments and supplements do not
unnecessarily extend the timeline or cost required to achieve the Primary
Regulatory Approval Goals.
(d)    Development Plan: New Activities.
(i)    During the Term, either Party can propose that additional Development
activities that are outside the scope of the Development Plan and not covered by
the provisions of clause (c)(i) above, including any new Trials for new
indications, be conducted under the Development Plan and the Development Budget.
If such Party and the other Party agree in writing upon such additional
Development activities, the Development Plan and the Development Budget shall be
amended in writing by the Parties to reflect such agreement of the Parties, and
all additional costs and expenses associated with such Development activities
shall, unless the Parties otherwise agree, ***.
(ii)    In the event that the Parties do not reach agreement with any such
additional Development activities described in clause (i) above, *** shall have
the right, in its sole discretion, to complete the activities at its own cost
and expense, provided any such new activities shall not interfere with the
ability of the Parties ability to timely achieve the Primary Regulatory Approval
Goals.
(e)    Arbitration Procedure. If either Party is entitled to submit a disputed
matter to arbitration pursuant to this Section 3.1.3 in accordance with the
provisions

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of this Section 3.1.3, it may do so by providing written notice to the other
Party of its election to submit such matter to arbitration in accordance with
this Section 3.1.3(e). Within *** days following notice by either Party to the
other of its election to submit such matter to resolution pursuant to the
provisions of this Section 3.1.3(e), the Parties shall each submit their
respective proposals with respect to amendments and supplements to the
Development Plan and the Development Budget to each other and to an independent
arbitrator or expert having substantial relevant experience with respect to
(i) the budgeting for, planning of and conduct of Trials for biologics of the
nature, stage of development, location, and size contemplated by this Agreement
and the Development Plan, (ii) regulatory compliance and communications with
applicable Regulatory Authorities, or (iii) Development and Manufacturing of
pharmaceutical products (including expertise with respect to CMC Information),
as applicable, which arbitrator shall be mutually acceptable to the Parties (or
failing such agreement, the Parties shall ask the American Arbitration
Association to promptly appoint the expert on behalf of the Parties) (the
“Expert Arbitrator”). If a Party fails to submit a proposal within such
timeframe, then the proposal of the submitting Party shall prevail. Each Party
shall have *** days from receipt of the other Party’s submission to submit a
written response to such proposal and, at a hearing to take place on no more
than *** Business Days and to commence no later than *** days after submission
of the written responses, each Party shall have a reasonable period of time, to
be determined by the Expert Arbitrator (which period of time shall be sufficient
for the Expert Arbitrator to fully understand the proposals and the relative
merits thereof), to argue for its proposal before the Expert Arbitrator. The
arbitrator(s) shall have the right to meet with the Parties together, as
necessary to make a determination. The Expert Arbitrator shall, within *** days
after the submission of the responses, or such longer period as the Parties may
agree, select the single proposal that, in the determination of the Expert
Arbitrator, as a whole is the most consistent with the requirements of this
Agreement and the matters relating thereto, and is the most fair and reasonable
to the Parties in light of the totality of the circumstances and the terms of
this Agreement (the Party that submitted such proposal selected by the
Arbitrator, the “Prevailing Party” and the other Party, the “Non-Prevailing
Party”). The Parties acknowledge and agree that the rendering of a determination
by the Expert Arbitrator shall be deemed effective at the time its determination
is made, irrespective of if and when a formal written statement of the Expert
Arbitrator’s opinion with respect to such matter, or the basis of its
determination, is released. At any time prior to the determination, either Party
may accept the other Party’s position on any unresolved issue. The Parties shall
inform the Expert Arbitrator of such accepted position and in such event such
position will be deemed part of the final resolution of the matter in dispute
and no longer subject

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to arbitration. The Expert Arbitrator’s decision shall take into account
customary and commercially reasonable industry practices for the conduct of
Development activities in compliance with Applicable Law. Any fees, costs,
expenses or other amounts payable to the Expert Arbitrator in connection with
any arbitration pursuant to this Section 3.1.3(e) shall be borne by the
Non-Prevailing Party.
(f)    For the avoidance of doubt, the Parties acknowledge and agree that the
resolution of any disputes with respect to the matters contemplated by this
Section 3.1.3 shall be resolved exclusively in accordance with the provisions of
this Section 3.1.3 and the provisions of Section 11.13 shall not be applicable
with respect to any such matters.
3.1.4.    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.
3.1.5.    Sponsor.
(a)    Sponsorship and Responsibilities. During the Term, OPKO will be the
regulatory sponsor of a Trial in all countries in the Territory where any Trial
is conducted as specified in the Development Plan, except to the extent that the
JDC has determined that Pfizer should be the regulatory sponsor, in which case
Pfizer will then 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 and Pfizer will each use Commercially Reasonable Efforts to perform
its respective obligations under the Development Plan, and shall conduct all
activities allocated to it under the Development Plan and this Agreement in
compliance with the Development Plan, all Applicable Laws and obligations
imposed by any Regulatory Authorities (including GCP) and the terms of this
Agreement.
3.1.6.    Approved CROs and Approved Vendors.
(a)    Approved CROs. Except as otherwise provided herein, OPKO may delegate any
of its responsibilities described in Section 3.1.5 to one (1) or more

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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 3.1.5(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 3.1.5(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 3.1.6 shall also apply
to Pfizer in circumstances where Pfizer is a regulatory sponsor of a Trial.
3.1.7.    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 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 3.1.2(e) and updates
regarding intellectual property issues relating to any Compound or Licensed
Product.
3.1.8.    Pfizer Retained Rights. Except as contemplated by the Development
Plan, Pfizer shall have sole authority over and control of the Development of
Compounds and Licensed Product.

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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 3.1.3:
(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 discussing and making suggestions in response to
any notifications described in Section 3.2.4;
(b)    review and approve amendments and modifications to the Development Plan
as contemplated herein; and
(c)    exchange and review Development, regulatory, Manufacturing and
Commercialization updates and information, as well as disclosures of developed
intellectual property; and perform, or delegate to a Party (in the JDC’s
discretion), such other duties as are specifically assigned to the JDC under
this Agreement.
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.

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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 the Development Plan, including any
Approved CRO or Approved Vendor.

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(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 *** 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. 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. 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 to the extent provided in Sections 3.1.1 and 3.1.3, 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

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BLA and all subsequent supplemental filings and Regulatory Approvals for all
Compounds and Licensed Products, including preparing all reports necessary as
part of a 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. During the Trials, 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 planed 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 submissions of BLAs, OPKO will provide
reasonable support in the preparation of the relevant sections related to OPKOs
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
Trial 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

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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, 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
submissions by Pfizer, OPKO shall provide the JDC with a copy of all such report
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 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.

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(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.
(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

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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), 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 for 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 derived datasets, SAP, Data
Management Plan, statistical programming plan and other Trial Master File
documents.
(c)    Test Data Transfer. Within *** 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

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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

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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 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 Execution Date, *** 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 Supply
Agreement containing customary terms to be mutually agreed upon by the Parties
(the “Supply Agreement”), provided that all *** and a quality agreement
reasonably acceptable to each Party in form and substance (the “Quality
Agreement”). *** shall also supply ***. 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

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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 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.    Transfer of Regulatory Filings and Other Data Following Regulatory
Approval. 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 PSGA, for any Licensed Product in the ***, as
applicable:
3.7.1.    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.    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

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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 Effective Date, unless otherwise
agreed in writing by the parties, Pfizer shall create and adhere to a
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 Pricing 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

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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 and/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.  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 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.

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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 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 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 conduct all Trials
initiated following the Effective 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 *** of the 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 (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 Execution Date and until such time as the
Pharmacovigilance Agreement is executed, within *** Business Days of providing
any notification to the JDC

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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 future Trials, OPKO will conduct,
or ensure that each Approved CRO conducts, all 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
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 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

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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 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.
4.2.8.    Obligations During Trial Conduct.
(a)    From and after the 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.

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(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 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 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

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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 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 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 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.

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(c)    If, at any time following the Effective Date, OPKO decides to change the
format of the database for any 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 the 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 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 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 Effective Date, 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”).
4.6.    Specimens. Unless otherwise requested by Pfizer, from and after the
Effective Date, OPKO (or its designated CRO) will test, store, or manage all
biological samples and/or associated slides or blocks (collectively,
“Specimens”).

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4.7.    Audits.
4.7.1.    From and after the 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 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 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 Effective
Date (each a “Monitoring Plan”). Within *** days following the 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 Effective Date, OPKO will be solely responsible for
responding to all queries from the IRBs and other ethics committees; provided
that (a) Pfizer

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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.
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 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

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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 to Pfizer a “topline” report, an “interim study” report, if
available, and a final complete study report, as well as any other reports as
may be contemplated by the Development Plan, each in accordance with the
timelines for delivery and content requirements as are set forth in the
applicable statistical analysis plan and Development Plan, including any
applicable protocols or statistical study requirements set forth therein. 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. Within *** days following the Effective Date, Pfizer
shall make 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”).
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 in ***
***
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 in ***
***
First achievement of *** of a Licensed Product for an Approved Indication in ***
***

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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, *** 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 and the *** 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 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).

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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.

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

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

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

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

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*** 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 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 *** (whether the *** or the *** Profit
Share Term, as applicable), then following the occurrence of such *** and
continuing until the *** anniversary of the commencement of such Profit Share
Term(s), each threshold dollar amount set forth in the left-hand-most column of
the table set out below in this Section 5.4 applicable *** shall be reduced by
an amount equal to *** were realized *** 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

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directly or indirectly *** with respect to, ***, including through the
effectuation of an *** agreement *** (ii) there is a subsequent ***, and (iii)
such *** had worldwide Net Sales for the *** 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 involving another Person that ***, (ii) there is a subsequent ***,
and (iii) such *** period prior to the date of *** that were less than *** of
the worldwide Net Sales of the *** for the same *** period, then following the
occurrence of such *** and continuing until the *** anniversary of the
commencement of the profit share term ***, each threshold dollar amount set
forth in the left-hand-most column of the table set out below in Section 5.4
applicable *** shall be reduced only by an amount equal to the difference
between (i) the amount of *** which were realized *** during the *** period
immediately preceding the occurrence of such *** and (ii) the amount of ***
during the same *** period.
*** 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.

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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 3.1.3,
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 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.
(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

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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.
5.6.    Taxes and Payments.
5.6.1.    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;

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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”).
5.6.2.    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 5.6.2, 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.
5.6.3.    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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***
***
***
***
***
***
***
***
***
***
***
***
***
***

5.7.    Inspection of Records.
5.7.1.    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.
5.7.2.    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 5.7.2 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.

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5.7.3.    Overpayments/Underpayments. If, after conducting an audit pursuant to
Section 5.7.2, 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 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.
5.8.    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 5.8 shall be deemed to be Pfizer’s Confidential Information and subject
to the provisions of Article 7.
5.9.    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 Effective Date, or that are Controlled by such Party on
or after the Effective Date and are outside the scope of this Agreement. For the
avoidance of doubt, as between the Parties, OPKO shall retain sole and

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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
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.

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(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 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.
(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

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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
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

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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

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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 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 this
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

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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 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.

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(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 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

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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 1.96, at least once every *** or earlier upon the
reasonable request of the other Party.
6.4.    Enforcement and Defense of Patent Rights.
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.  

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(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

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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 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 ***
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.

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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.
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

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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
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.

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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 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.

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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 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 the 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

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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 *** days in the event OPKO can, within *** days 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 “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 ***
days 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.

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8.1.    Mutual Representations and Warranties. Each of OPKO and Pfizer hereby
represents and warrants to the other Party, as of the Execution Date and as of
the Effective 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 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 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 Execution Date and as of the 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

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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 1.96 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;

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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 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 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

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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;
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 Effective Date
until expiration or termination of this Agreement, other than in connection with
the Agreement:

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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 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 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

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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 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 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

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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.

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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.
9.
TERM AND TERMINATION.

9.1.    Term. The term of this Agreement (the “Term”) will commence on the
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

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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 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.    Termination Prior to the License Effective Date. If this Agreement is
terminated by either Party for any reason (including in the event of HSR Filing
denial pursuant to Section 11.2) prior to the Effective Date, then except as
otherwise expressly

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provided herein, all rights, licenses and sublicenses granted by either Party to
the other Party hereunder will cease and each of the Parties will be relieved of
its duties and obligations arising under this Agreement after the date of such
termination.
9.5.2.    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 9.5.3 shall only
apply to the ***, and this Agreement shall remain in full force and effect in
accordance with its terms in *** of the Territory.
9.5.3.    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 the Pfizer Developed IP 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 9.5.3(a), and neither Party will have any liability to the other
for failure to do so.
(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
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
pharmacoviligence, 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 and Licensed Products to OPKO, to be reflected in a commercially
reasonable

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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 pharmacovigilence 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, (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,
Pricing 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.

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(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.
(i)    In the event of a termination of a *** or this Agreement in its entirety,
except to the extent that Pfizer continues to supply 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
9.5.3(h)(i) “commercially reasonable terms” means, with respect to clinical
supplies of Compound and Licensed Products, *** for such supplies, and with
respect to commercial supplies means *** 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.

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(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 9.5.3(h) (ii), no fewer than *** prior to the
effective date of termination, and (B) *** Solely for purposes of this
Subsection 9.5.3(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 after the effective date of such termination, and OPKO shall continue
to receive royalties and gross profit payments with respect to such sales.
9.5.4.    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
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 Product in such
*** shall cease.
9.5.5.    Confidential Information. Following any termination of this Agreement,
each of Pfizer and OPKO shall, upon request of the other Party, return or
destroy all

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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.
9.5.6.    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.
9.5.7.    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 9.5.7 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), 5.7 (Inspection of Records), 5.9 (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 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

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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

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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 the Development or Manufacture of the Licensed Product at
any time prior to the 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

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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 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.

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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 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

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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.
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 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

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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

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

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:

Blaine Templeman
Arnold & Porter LLP
399 Park Avenue
New York, NY 10022-4690
Office: 212.715.1122
blaine.templeman@aporter.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.

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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.
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 either Party may initiate litigation to
resolve the dispute.
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.

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11.14.    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.
11.15.    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.
11.16.    No Jury Trial. THE PARTIES EXPRESSLY WAIVE AND FOREGO ANY RIGHT TO
TRIAL BY JURY.
11.17.    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 between the
Parties, dated *** (the “CDA”), which is hereby terminated as of the Effective
Date. The Parties acknowledge and agree that, as of the 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.
11.18.    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

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that if a court of competent jurisdiction or an arbitrator should determine
that, notwithstanding the terms of this Section 11.18, 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.
11.19.    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.
11.20.    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.
11.21.    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.
11.22.    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 this Agreement, 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 this Agreement, including in relation to
Pfizer’s exercise of its rights under this Agreement, (collectively, (i) and
(ii) the “Parent Guaranty”).  This Parent Guaranty is an irrevocable guaranty of
payment 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 (a) 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, (b) the bankruptcy, receivership, insolvency,
reorganization or similar proceedings involving or affecting OPKO, or (c) 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,

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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]

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

PFIZER INC.

By:    
Name:
Title:
OPKO IRELAND LTD.

By:    
Name: Brian V. Elliott
Title: Director

As a party to this Agreement solely with respect to
the provisions of Section 11.22:

OPKO HEALTH, INC.

By:     
Name:
Title:

 
 

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Schedule 1.32 – Compounds
Schedule 1.53 – ***
Schedule 1.70 – Genotropin Products
Schedule 1.85 – ***
Schedule 1.96 – Licensed Patent Rights
Schedule 1.177 – ***
Schedule 5.4 – Example Profit Share Calculation
Schedule 8.3 – OPKO Disclosure Schedule

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

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 1.32 – Compounds
***

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 1.53 – ***
Each of the following countries:
***

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confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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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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confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 1.85 – ***
Each of the following countries:

***

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 1.96 - Licensed Patent Rights

(a) - Licensed hGH-Specific Patents

U.S. Patents and Applications

***

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confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Patents and Applications Outside of U.S.

***

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confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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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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confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 1.177 – ***
***

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 5.4 – Example Profit Share Calculation
***

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confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Schedule 8.3 – OPKO Disclosure Schedule

***

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Exhibit A – Development Plan

***

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Exhibit B – Development Budget

***

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Exhibit C – Press Release

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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Proprietary and confidential
FINAL DRAFT– hGH Release
12-14-14

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

•
Upon Pfizer’s commercialization of hGH-CTP, OPKO is eligible to receive royalty
and/or profit sharing payments

•
Pfizer to obtain exclusive license to commercialize hGH-CTP globally

Miami, FL, and New York, NY, December 15, 2014 - 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 an 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.

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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"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 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 of 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
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

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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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.
OPKO 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, whether OPKO will
receive royalty and/or profit sharing payments for sales from hGH-CTP,
expectations about the global growth hormone market, whether hGH-CTP has the
potential to be the best in class long-acting growth hormone product, 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.
PFIZER DISCLOSURE NOTICE: The information contained in this release is as of
December 15, 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

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.

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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.

 

 

*** = Portions of this exhibit have been omitted pursuant to a request for
confidential treatment.  An unredacted version of this exhibit has been filed
separately with the Commission.