Factor IX Research, Development And License

Exhibit 10.33


Portions of this exhibit were omitted and filed separately with the Secretary of the Commission pursuant to an application for confidential treatment filed with the Commission pursuant to Rule 24b-2 under the Securities Exchange Act of 1934. Such portions are marked by a series of asterisks.


RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT


BETWEEN


NEOSE TECHNOLOGIES, INC.


AND


NOVO NORDISK A/S


DATED AS OF NOVEMBER 2, 2007


****** - Material has been omitted and filed separately with the Commission.


TABLE OF CONTENTS


Page


1.

DEFINITIONS

1


2.

CONDUCT OF THE PROJECT AND COMMERCIALIZATION EFFORTS

8


3.

FEES AND DEVELOPMENT PAYMENTS

10


4.

PRODUCT PAYMENTS AND ROYALTIES

12


5.

INTELLECTUAL PROPERTY GRANTS AND RIGHT OF NEGOTIATION

15


6.

OWNERSHIP OF INTELLECTUAL PROPERTY

17


7.

BLOCKING PATENTS

27


8.

SUPPLY AGREEMENT

29


9.

CONFIDENTIALITY

29


10.

REPRESENTATIONS AND WARRANTIES

30


11.

INDEMNIFICATIONS AND LIMITED LIABILITY

31


12.

TERM AND TERMINATION

33


13.

DISPUTE RESOLUTION

35


14.

GOVERNMENT APPROVAL

35


15.

COVENANTS

36


16.

MUTUAL COOPERATION

37


17.

MISCELLANEOUS

37


****** - Material has been omitted and filed separately with the Commission.


RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT


This RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT (" Agreement" ), is dated as of November 2, 2007 (the " Effective Date" ), between Neose Technologies, Inc., a Delaware corporation (" Neose" ), and Novo Nordisk A/S , a Danish corporation (" Novo" ).


BACKGROUND


Novo and Neose are parties to a Research, Development and License Agreement dated November 17, 2003, as amended by letter agreements dated December 18, 2003, October 12, 2004, and February 16, 2005, and by Amendment Number 4 dated February 21, 2006 (collectively, the " Amendments" ), to develop next generation recombinant coagulation Factor VIII and Factor IX (as so amended, the " Original Agreement" ).


Novo and Neose desire to amend and replace the Original Agreement with two agreements to separate the agreements of the parties with respect to each of Factor VIII and Factor IX, to incorporate the terms of the Amendments as applicable in each case, and to make further changes as the parties agree. This Agreement supersedes the Original Agreement with respect to coagulation Factor IX. Contemporaneously with the execution and delivery of this Agreement, Neose and Novo have entered into a Research, Development and License Agreement, superseding the Original Agreement with respect to Factor VIII (the " Factor VIII Agreement" ).


Neose and Novo have also entered into an Amended and Restated Research, Development and License Agreement, dated October 31, 2006, pursuant to which Novo and Neose are collaborating to develop a long-acting Factor VIIa compound (the " Factor VIIa Agreement" ).


TERMS


NOW, THEREFORE, in consideration of the premises and of the mutual agreements and covenants contained in this Agreement, and intending to be legally bound hereby, Novo and Neose agree as follows:


1. DEFINITIONS. Capitalized terms not otherwise defined shall have the meaning set forth in this Section 1 .


1.1 " Affiliate" means, with respect to any Person, any other Person that directly or indirectly controls, is controlled by, or is under common control with, such Person. Without limiting the foregoing, a Person shall be regarded as in control of another Person if it owns, or directly or indirectly controls, more than fifty percent (50%) of the voting stock or other ownership interest of the other Person.


1.2 " Blocking Patent" means any Patent Rights claimed to be owned or Controlled by a Third Party with respect to which Patent Rights an assertion is being made by or on behalf of the Third Party that the use of the Neose Technology under this Agreement infringes such Person' s Patent Rights.


1.3 " Calendar Quarter" means any of the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 or December 31 during the Term.


****** - Material has been omitted and filed separately with the Commission.


1.4 " Calendar Year" shall mean the respective periods of twelve (12) consecutive calendar months ending on December 31 during the Term.


1.5 " Carved Factor IX Claims" shall mean any Potential Carved Factor IX Claim with respect to which the parties have filed, in accordance with Section 6.4.2 , a separate patent application. 1.6 " Commercially Reasonable Efforts" shall mean efforts and resources normally used by a Party in similar undertakings, taking into account the proprietary position of the product or technology involved, the regulatory structure involved, the profitability of such undertaking, the competitiveness of the relevant marketplace, and other relevant factors.


1.7 " Commercial Sale" means any sale of a New Product by Novo, its Affiliates, or Sublicensees to a Person other than their respective Affiliates or Neose.


1.8 " Confidential Information" shall mean any of the Disclosing Party' s proprietary or confidential information, technical data, trade secrets or know-how, including, but not limited to, research, product plans, products, the identity of the Novo Materials, information relating to the Novo Materials, service plans, services, customer lists and customers, markets, software, developments, inventions, processes, formulas, technology, designs, drawings, engineering, marketing, distribution and sales methods and systems, sales and profit figures, finances and other business information disclosed to the Recipient by or on behalf of the Disclosing Party, either directly or indirectly, in writing, orally or by drawings or inspection of documents or other tangible property.


1.9 " Control" or " Controlled" means possession of the ability of one party to grant the licenses or sublicenses to the other party as provided for herein without violating the terms of an agreement or other arrangement with a Third Party existing before or after the Effective Date.


1.10 " Designated Representative" means, in the case of Neose, its Vice President, Business Development, or such other person designated by Neose in writing from time to time to Novo, and, in the case of Novo, its Executive Vice President and Chief Science Officer, or other such other person designated by Novo in writing from time to time to Neose.


1.11 " Disclosing Party" is used as defined in Section 9.1.


1.12 " Effective Date" means the date hereof. 1.13 " Factor VIIa Agreement" has the meaning set forth in the Background section. 1.14 " FDA" means the United States Food and Drug Administration and any successor agency.


1.15 " Field of Use" means the development and commercial manufacture of New Products for ******.


1.16 " GMPs" shall mean current good manufacturing practices for the methods to be used in, and the facilities and controls to be used for, the manufacture, processing, packing


****** - Material has been omitted and filed separately with the Commission.


2


and holding of biological products, all as set forth from time to time by the FDA, including all amendments and supplements thereto throughout the term of this Agreement.


1.17 " Improvements" means any and all developments, discoveries, inventions, additions, amendments, modifications, ideas, processes, methods, compositions, formulae, techniques, information and data, whether or not patentable, conceived, developed or reduced to practice, that improve or beneficially change, or enhance the economic and technical attributes of, any Know-How or Patent Rights or any process, device or composition.


1.18 " IND" means an application for an Investigational Exemption for a New Drug filed with the FDA, or any comparable filing made with a regulatory authority outside the United States.


1.19 " Joint Improvements" means any and all Improvements made, conceived or reduced to practice jointly by Neose and Novo in the conduct of the Original Work Plan under the Original Agreement or the Work Plan under this Agreement, whether patentable or not, other than Neose Improvements and Novo Improvements.


1.20 " Know-How" means any and all formulae, procedures, processes, methods, designs, know-how, show-how, trade secrets, discoveries, inventions (whether or not patentable), patent applications, licenses, software and source code, programs, prototypes, designs, discoveries, techniques, methods, ideas, concepts, data, engineering and manufacturing information, electronic control circuits, specifications, diagrams, drawings, schematics, blueprints and parts lists and other proprietary information, rights and works of authorship, whether or not reduced to writing.


1.21 " M1 Profile for the New Factor IX Product" means the parameters for candidate selection required for PEG-F9 set forth on Exhibit 1.21 , as amended from time to time in accordance with Section 2.2 .


1.22 " Mutual Nondisclosure Agreement" means the Amended and Restated Mutual Nondisclosure Agreement between the Parties dated November 25, 2002.


1.23 " Neose Exclusive Compounds" shall mean any and all forms of ****** including, but not limited to, with respect to either of the foregoing: full length proteins, truncated proteins, fusion proteins, analogs, mutants, splice variants, and conjugates with other molecular entities such as proteins, peptides, organic or inorganic substances. 1.24 " Neose Improvements" means any and all Improvements relating to the Neose Technology made, conceived, or reduced to practice by (i) either Neose or Novo or both in the conduct of the Original Work Plan under the Original Agreement or the Work Plan under this Agreement, (ii) either Neose or Novo or both under this Agreement, (iii) Novo in the practice of any Neose Technology under the licenses granted to Novo in Section 5.1 , or (iv) Novo in the conduct of any activity using any Ownership Rights assigned to Novo pursuant to Section 6.4.1 , in each case of (i), (ii), (iii) or (iv), other than the Novo Materials, the Novo Materials modified using the Neose Technology and New Product. Specifically excluded from " Neose Improvements" are (1) formulations, combinations and methods of treatment to the extent relating to Novo Materials, the Novo Materials modified using the Neose Technology and New Products and (2) analytical techniques and purification methods invented, developed or reduced


****** - Material has been omitted and filed separately with the Commission.


3


to practice solely by Novo that did not originate from or are not derived from Neose (collectively, the " Techniques" ).


1.25 " Neose Improvement Claim" shall mean any Neose License Claim that relates to a Neose Improvement. 1.26 " Neose Intellectual Property" means Neose Technology and the Neose Improvements. 1.27 " Neose License Claim" shall mean a claim in or supportable by Patent Rights listed in Exhibit 1.27 (including any Patent Rights claiming priority to such listed rights) and Controlled by Novo encompassing within its scope: (i) any methods of ****** ; (ii) any compositions-of-matter or methods of treatment specifically naming Neose Exclusive Compounds derived from or used in the practice of such methods described in clause (i) above; (iii) any compositions-of-matter or methods of treatment related to any compound other than the Neose Exclusive Compounds, any and all forms of ****** , or Novo Materials derived from or used in the practice of such methods described in clause (i) above; wherein any claim encompassed by clauses (i), (ii) or (iii) must also be encompassed within the scope of a claim supportable by any Patent Right listed in the listing of patents and patent applications dated October 31, 2006 which had been certified by Neose and delivered to Novo prior to such date; or (iv) any Neose Improvements made or reduced to practice by Novo. 1.28 " Neose Patents" means (a) all Patent Rights relating to methods and processes for glycosylation design and remodeling of proteins, peptides and antibodies that are Controlled by Neose, including, but not limited to, (i) the Patent Rights listed in Exhibit 1.28 , (ii) the Patent Rights developed by Neose in the conduct of the Original Work Plan during the term of the Original Agreement or in the conduct of the Work Plan during the Term of this Agreement, and (iii) any later acquired Patent Rights Controlled by Neose and used to develop any New Product; and (b) all Patent Rights Controlled by Neose that would be infringed by the research, development (including clinical development), manufacture, making, use, marketing, promotion, sale, offer for sale, distribution, import and export of New Products in the Territory.


1.29 " Neose Project-Related Costs" means Neose' s costs of conducting the Original Work Plan and the Work Plan, which shall be determined in accordance with the Original Agreement or this Agreement, as applicable, and calculated as follows: (i) with respect to personnel, at the rate of ******; and (ii) with respect to materials, at the ******.


1.30 " Neose Technology" means the Neose Patents and any Know-How Controlled by Neose relating to methods and processes for the ******, including, without limitation, its GlycoAdvanceae, GlycoPEGylation99 and GlycoConjugation99 technologies, and other ****** processes, and all Know-How resulting from work conducted by Neose during the Term.


1.31 " Net Sales" means proceeds from Commercial Sales of New Products by Novo, its Affiliates or Sublicensees to Third Parties, after deducting (to the extent actually incurred or reasonably estimated and accrued in accordance with Generally Accepted Accounting Principles in the United States and to the extent not already deducted in the amount invoiced): (i)


****** - Material has been omitted and filed separately with the Commission.


4


reasonable trade, cash and quantity discounts or rebates (other than price discounts granted at the time of sale), reasonable service allowances and reasonable required agent' s commissions, if any, allowed or paid, (ii) credits or allowances actually given or made for rejection or return of previously sold products or for retroactive price reductions (including Medicare, Medicaid, and/or discounts and similar types or rebates and/or discounts), (iii) taxes, duties or other governmental charges levied on or measured by the billing amount (excluding income and franchise taxes), as adjusted for rebates and refunds, and (iv) charges actually incurred for freight and insurance directly related to the distribution of New Products (excluding amounts reimbursed by Third Party customers). A " Commercial Sale of a New Product" is deemed to occur when the invoice is issued, or if no invoice is issued, upon the earlier of shipment or transfer of title in the New Product to a Third Party. In the event that New Product is sold or distributed for use in combination with or as a component of another product or products (a " Combination Product" ), the calculation of Net Sales from such Combination Product shall be determined as set forth below:


If all of the active ingredient components of a Combination Product are also sold separately and in identical strengths to those contained in the Combination Product, then the following shall apply: Net Sales shall be calculated as set forth above on the basis of the gross invoice price of a New Product containing the same weight of the licensed active ingredient constituent sold independently [A], divided by the sum of the gross invoice price of all of the active ingredient constituents sold independently [B + A], multiplied by the gross invoice price of the Combination Product, as shown by the following formula:


Net Sales =

[A]


x

[gross invoice price of the Combination Product]


[B + A]


The distribution costs associated with any Combination Product will be allocated in the same proportion among the licensed active ingredient components and all other active ingredient components.


If the active ingredient components of a Combination Product are not sole separately in identical strengths to those contained in the Combination Product, then the parties agree to negotiate in good faith the calculation of Net Sales with regard to such Combination Product.


1.32 " New Product" shall mean the following: (a) any of the Novo Materials modified using either (i) the Neose Technology, (ii) any Neose Improvements, or (iii) any combination of all or some of (i) and (ii) above, and (b) any Novo Materials covered by any Carved Factor IX Claims (except to the extent such claims constitute Novo Improvements).


1.33 " Novo Improvements" means any and all Improvements that are related to the Novo Materials and/or any of the New Products made, conceived or reduced to practice by Novo or Neose or both, other than Neose Improvements.


1.34 " Novo Materials" means any and all forms of FIX, including, but not limited to, ******, such as ******.


****** - Material has been omitted and filed separately with the Commission.


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1.35 " Novo Technology" means the Patent Rights and Know-How Controlled by Novo relating to the Novo Materials.


1.36 " Original Date" means November 17, 2003, the date of execution of the Original Agreement. 1.37 " Original Work Plan" means the " Work Plan," as defined in the Original Agreement, to the extent relating to Factor IX. 1.38 " Ownership Rights" means any and all right, title and interest under patent, copyright, trade secret and trademark law, or any other intellectual property or other law, in and to any Know-How, Patent Rights, or Improvements.


1.39 " Parties" means Neose and Novo, collectively.


1.40 " Party" means Neose or Novo, as the context requires, or each of Neose and Novo, individually.


1.41 " Patent Rights" shall mean individually and collectively any and all patents and/or patent applications and provisional applications, all inventions disclosed therein, and any and all continuations, continuations-in-part, continued prosecution applications, divisions, renewals, patents of addition, reissues, confirmations, registrations, revalidations, revisions and re-examinations thereof, utility models, petty patents, design registrations and any and all patents issuing therefrom and any and all foreign counterparts thereof and extensions of any of the foregoing including without limitation extensions under the U.S. Patent Term Restoration Act, extensions under the Japanese Patent Law, and Supplementary Protection Certificates (SPCs) according to Counsel Regulation (EEC) No. 1768/92 and similar extensions for other patents under any applicable law in any country of the world.


1.42 " Permit" means any governmental or regulatory filing, submission, approval, permit or license that is required by applicable law in any jurisdiction worldwide for clinical trials, Commercial Sales or other use of any of the New Products.


1.43 " Person" means an individual, corporation, partnership, trust, business trust, association, joint stock company, joint venture, pool, syndicate, sole proprietorship, unincorporated organization, government, governmental agency, authority or instrumentality, or any other form of entity not specifically listed in this Agreement.


1.44 " Potential Carved Factor IX Claims" shall mean ****** . 1.45 " Product-Candidate" means any new ****** product-candidate Controlled by Neose during the Term.


1.46 " Project" means the project to be conducted hereunder by the Parties in accordance with the Work Plan.


1.47 " Project Manager" means the project managers described in Section 2.4.1 .


****** - Material has been omitted and filed separately with the Commission.


6


1.48 " Reagents" means the enzymes and sugar nucleotides required to use the Neose Technology in the manufacture of New Products.


1.49 " Recipient" is used as defined in Section 9.1 .


1.50 " Regulated Market" means any jurisdiction worldwide that requires a Permit for clinical trials, Commercial Sales or any other use of a New Product.


1.51 " Regulatory Approval" means any marketing authorization (including authorizations approving a Biologics License Application) required for a New Product, exclusive of any pricing or third-party reimbursement approval.


1.52 " Required Agreement" means any agreement with a Sublicensee required under Section 5.1.3 .


1.53 " ******" ****** . 1.54 " Steering Committee" means the steering committee established pursuant to Section 2.4.2 , or any successor group appointed by the Parties.


1.55 " Sublicensee" means a sublicensee of Novo' s rights under Section 5 .


1.56 " Supply Agreement" means the supply agreement to be entered into between Neose and Novo in accordance with Section 8 .


1.57 " Territory" means the world.


1.58 " Term" means the term of this Agreement, which shall commence on the Effective Date and shall expire or terminate as described in Section 12 .


1.59 " Third Party" means any Person other than Novo, Neose, or their respective Affiliates.


1.60 " Valid Patent Claim" means a claim of an issued and unexpired patent forming part of the Neose Patents or the Carved Factor IX Claims that has not been held revoked, unenforceable or invalid by a decision of a court or other government agency of competent jurisdiction, or unappealable or unappealed within the time allowed for appeal, or which has not been admitted to be invalid or unenforceable through reissue or disclaimer or otherwise. For the purposes of determining royalties due and payment obligations under this Agreement, any claim being prosecuted in a pending patent application included in the Neose Patents or the Carved Factor IX Claims shall be deemed a Valid Patent Claim, provided that such claim is not pending, other than because of any action taken by Novo or an Affiliate of Novo, ****** in which the subject matter of the claim is disclosed, after which period it shall cease to be considered a Valid Patent Claim until the patent issues.


1.61 " Work Plan" means the Work Plan attached hereto as Exhibit 2.2 , and, unless otherwise specified, as amended from time to time in accordance with Section 2.2 .


****** - Material has been omitted and filed separately with the Commission.


7


2. CONDUCT OF THE PROJECT AND COMMERCIALIZATION EFFORTS 2.1 Conduct. Commencing promptly after the Effective Date, Neose and Novo shall use Commercially Reasonable Efforts to carry out their respective obligations under the Work Plan.


2.2 Creation and Modification of Work Plan. Attached hereto as Exhibit 2.2 is the Work Plan, setting forth a project summary and timetable for the research and development, scale-up and technology transfer activities to be conducted under this Agreement. Neose shall be responsible for the development of validated, GMP processes for the production of Reagents for use in the manufacture of New Products and protocols for the use of the Reagents in the manufacture of New Products by Novo, all as set forth in Exhibit 2.2 . The Work Plan may be amended or modified from time to time, but only in a writing signed by each Party' s Designated Representative and specifying the Parties' estimate of any additional Neose Project-Related Costs that will be paid by Novo as a result of such amendment.


2.3 Funding. 2.3.1 Work Plan Costs. Through the date hereof, Novo has funded the Neose Project-Related Costs under the Original Work Plan, plus the cost of materials, and, from and after the Effective Date, Novo will fund the Neose Project-Related Costs under the Work Plan, plus the cost of materials. If the Parties amend the Work Plan in a manner that requires any new product or service to be provided by Neose ( e.g ., a new Reagent, expression system, scale up activity) which is not currently incorporated in the Work Plan, the Parties shall agree in writing on any increase in the Neose Project-Related Costs that are authorized in connection with such amendment.


2.3.2 Payment. Novo will pay for the Neose Project-Related Costs ******. No earlier than thirty (30) days before the beginning of each Calendar Quarter, Neose will invoice Novo for such amount based on a budgeted estimate of Neose Project-Related Costs for such Calendar Quarter. Within thirty (30) days after the end of each Calendar Quarter, Neose shall submit to Novo a written report setting forth the actual Neose Project-Related Costs for such Calendar Quarter, and shall, as applicable, pay to Novo any amounts paid by Novo for such Calendar Quarter in excess of the actual Neose Project-Related Costs shown in such report, or invoice Novo for any additional amounts owed hereunder. Novo will pay all invoices delivered under this Section 2.3 within ****** after receipt.


2.4 Management of Project 2.4.1 Project Managers. Each of the Parties shall appoint a Project Manager, who will be its primary contact regarding the Project. The Project Managers on the date hereof are Jakob Back for Novo and David Hakes for Neose. The Project Managers shall keep each other reasonably informed of the progress under the Work Plan and shall be responsible for maintaining appropriate records of the deliberations and decisions of the Project Managers and the Steering Committee. The Project Managers shall be responsible for overseeing and directing the day-to-day activities conducted at their respective sites in accordance with the Work Plan and suggesting changes for consideration by the Steering Committee. A Party may


****** - Material has been omitted and filed separately with the Commission.


8


change its Project Manager at any time, and from time to time, effective upon notice to the other Party of such change.


2.4.2 Establishment and Responsibilities of Steering Committee. The Parties have established a Steering Committee to monitor the progress of the Work Plan, to evaluate and recommend to the Parties any proposed amendments or modifications to the Work Plan and the costs thereof, to approve and monitor compliance with any publication policy provided to it by Novo, and to carry out all other obligations assigned to it under this Agreement or by the Parties. Each Party may designate a co-chairperson and secretary of the Steering Committee. As of the date hereof, the Steering Committee consists of Sf8ren Bjf8rn, Michael Shalmi and Steen Weber Jensenrepresenting Novo and David A. Zopf, M.D., Kathryn J. Gregory and Elliot Morales, Jr. representing Neose.


2.4.3 Action by Steering Committee and Dispute Resolution. The Steering Committee shall consist of such number of members and alternate members as the Parties may determine from time to time. Each Party shall appoint fifty percent (50%) of the permanent and alternate members of the Steering Committee. The members of the Steering Committee shall include members of senior management of each Party. The members of the Steering Committee representing a Party and present at a meeting shall have one vote, collectively. If the Steering Committee cannot reach agreement on any matter, ****** shall be entitled to ******; provided, however, that if the Steering Committee cannot reach agreement on any matter involving a change in ...