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Exhibit 4.4    
  

 
 

Collaboration Agreement    
  

        COLLABORATION AGREEMENT dated this 18th day of December, 2002 by and between CRUCELL N.V. and CRUCELL HOLLAND B.V., both Netherlands corporations having offices
at Archimedesweg 4, 2333 CN, Leiden, The Netherlands (jointly and severally "Crucell") and DSM BIOLOGICS HOLDING, INC. and DSM BIOLOGICS COMPANY, INC., Quebec corporations having offices
at 6000 Royalmount Avenue, Montreal, Canada and DSM BIOLOGICS COMPANY, B.V., a Netherlands corporation having offices at Zuiderweg 72/2, Groningen, The Netherlands (jointly and severally "DSM"). 

R E C I T A L S: 

        A.    Crucell
is the owner of certain patents, know-how, expertise and other proprietary technology relating to the establishment and maintenance of a human cell
line (as more specifically defined herein, "PER.C6 Cells") which Crucell is developing as an expression platform for the development and manufacture of biopharmaceutical products. 

        B.    DSM
is engaged, among other things, in the contract development and manufacture of biopharmaceutical products. DSM desires to increase and improve its manufacturing
technology and capacity in order to provide product development and contract manufacturing services to the pharmaceutical and biopharmaceutical industries. 

        C.    In
order to further such development activities and increase their commercial applicability, Crucell and DSM desire to collaborate on the commercialization of PER.C6 Cell
technology and on the
development of large scale manufacturing technology utilizing PER.C6 Cells, in each case as an expression platform to produce research and commercial quantities of pharmaceutical products. To that
end, the parties have agreed to perform certain research and development activities, to grant certain licenses and to facilitate related technology transfers, all in accordance with the terms and
conditions hereinafter set forth. 

        NOW,
THEREFORE, in consideration of the foregoing and of the mutual terms and conditions hereinafter set forth, the parties hereto hereby agree as follows: 

        1.    Definitions.    In addition to terms defined hereinafter in this Agreement, as used herein the following terms
shall have the respective meanings set forth below: 

        1.1.  "Act"
shall mean the United States Federal Food and Drug Act and regulations promulgated thereunder, including current Good Manufacturing Practice regulations and
corresponding laws and regulations in other countries of the Territory. 

        1.2.  "Affiliate"
shall mean any person or legal entity controlling, controlled by or under common control with the person or entity with respect to which such status is at
issue. For this purpose "control" shall mean direct or indirect beneficial ownership of at least fifty percent (50%) of the voting share capital in such legal or other business entity. With respect to
DSM, control shall refer, without limitation, to control by DSM N.V. of Heerlen, The Netherlands. With respect to Crucell, control shall refer, without limitation, to control by Crucell N.V. of
Leiden, The Netherlands. 

        1.3.  "Claim"
shall have the meaning as defined in section 7.4. 

        1.4.  "Crucell
Collaboration Revenues" shall mean Collaboration Revenues received by Crucell from Licensees within the Field in the Territory on or after January 1,
2002. "Collaboration Revenues" shall be deemed to include milestone and other lump-sum or up-front royalty or license 

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payments but shall not be deemed to include research revenues or reimbursement for research or development activities performed by Crucell for Licensees. 

        1.5.  "Crucell
Technology" shall mean exclusively PER.C6 Cells, PER.C6 Patents, PER.C6 Know-How, Modified Cells and Modified Cell Know-How and new
generations of E1 immortalized human retina cells and related know-how. 

        1.6.  "Development
Milestone" shall mean a goal or objective of the Development Program, including, without limitation, the achievement of specific technological, commercial,
regulatory compliance, specific Product development or other specific milestones. A Development Milestone is a combination of the respective technical milestone and commercial milestone. The initial
Development Milestones shall be set forth in the Development Plan, as attached hereto. Furthermore and for clarity is an overview of the technical and commercial milestones attached hereto as
Schedule 1.6. 

        1.7.  "DSM
Collaboration Revenues" shall mean Collaboration Revenues received by DSM from Licensees within the Field in the Territory. "Collaboration Revenues" shall be
deemed to include milestone and other lump-sum or up-front royalty or license payments but shall not be deemed to include research revenues or reimbursement for research,
development or manufacturing activities or services performed by DSM for Licensees. 

        1.8.  "DSM
Technology" shall mean the DSM Patents and DSM Know-How owned by DSM and which DSM has rights to license, resulting from, acquired during or licensed
in connection with the Development Program which relate specifically to, or cover, Crucell Technology. 

        1.9.  "Effective
Date" shall mean January 1, 2002, reflecting the collaboration of the parties from and after such date in anticipation of the execution of this
Agreement. 

        1.10.    "exclusive"
shall mean, where used in connection with a specific grant of rights in respect of Patents or Know-How, that the granting party
(i) shall retain for itself no ability to use such property and (ii) shall have no ability to authorize its Affiliates or third parties (other than the grantee of such specific rights)
to use such property, in the geographic areas and field of use covered by, and for the term of, such grant. 

        1.11.    "FDA"
shall mean the United States Food and Drug Administration or any successor agency having comparable jurisdiction. 

        1.12.    "Field"
shall mean the production of proteins, including, but not limited to, monoclonal antibodies and (poly)peptides, and conjugates thereof, for the
development, manufacture, sale, use and distribution of Products, using Crucell Technology as the expression platform. "Field" shall not be deemed to include the production of viruses or
virus-like particles. 

        1.13.    "FTE"
shall mean, on an annual basis, the working man-hours equivalent to a full time employee. 

        1.14.    "Joint
Technology" shall mean Patents and Know-How resulting from or generated pursuant to the Development Plan, which shall be jointly owned
by DSM and Crucell as hereinafter provided. 

        1.15.    "Know-How"
shall mean information and materials, whether or not confidential and whether or not obtained through licenses, including
specifications, technical and non-technical manufacturing processes and equipment, data and information, processes, tests, results of tests or studies, methodologies, in any such case
however manifested or embodied, including all written, electronic and other tangible manifestations thereof. 

        1.16.    "Licensee"
shall mean any person or entity with a valid and subsisting Research or Commercial License permitting the use of Crucell Technology for the
research and development, 

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manufacture, marketing, sale or distribution of Products in any country of the Territory. A "Commercial License" shall mean a license with a Licensee permitting research, development, captive
manufacture of pre-clinical material and/or a specific Own Product and commercial sale and distribution of a specific Product; a "Research License" shall mean such a license permitting
only research and development activities, including captive production of pre-clinical and/or clinical material of Own Products. Unless otherwise mutually agreed by the parties, any
Commercial and Research License shall contain standard conditions and shall in all material respects contain and be consistent with the standard terms and conditions and format to be agreed upon by
the parties pursuant to Section 4.3. No third party shall be entitled or allowed by Crucell or DSM to have or use PER.C6 Cells or Crucell Technology in the Field other than by obtaining a
Research License, a Commercial License or by entering into an MTA. An "MTA" shall mean a material transfer agreement of which the format shall be agreed upon by the Business Development Committee, and
which will have a validity of no more than 9 months, which enables and entitles a third party, free of charge, to obtain and use PER.C6 Cells for evaluation purposes only. 

        1.17.    "Modified
Cells" means PER.C6 Cells modified by the introduction of nucleic acids to assist or improve PER.C6 Cells or new generations of E1 immortalized
human retina cells as so modified in expressing Products or components of Products. 

        1.18.    "Modified
Cell Know-How" means Know-How specifically related to Modified Cells, whether now owned by or in the possession of
Crucell or which is developed by or on behalf of, or otherwise comes into the possession of Crucell, during the term of this Agreement. 

        1.19.    "non-exclusive"
shall mean, when used in connection with a specific grant of rights in respect of Patents or Know-How, that the
granting party shall retain for itself the right to use such property and to authorize third parties (including both Affiliates and non-Affiliates) to use such property, in the geographic
areas and field of use covered by, and for the term of, such grant. 

        1.20.    "Own
Products" shall mean Products manufactured by an owner of the IND, BLA or equivalent files for regulatory bodies for such Products. 

        1.21.    "Patent"
shall mean patent applications and granted patents, including utility models, inventors' and authors' certificates, improvement patents and
patents of addition, and all foreign counterparts of them in any and all countries of the Territory, and including any divisionals, refilings, continuations,
continuations-in-part, reissues, reexaminations, extension and term restorations thereof, and applications therefore. 

        1.22.    "PER.C6
Cells" shall mean the cells deposited under ECACC No. 96022940, otherwise known as PER.C6. 

        1.23.    "PER.C6
Know-How" shall mean PER.C6 Cells and all Know-How related to PER.C6 Cells and the use of such cells to clone,
manufacture, isolate and purify Products, whether now owned by or in the possession of Crucell or which is developed by or on behalf of, or otherwise comes into the possession of Crucell, including,
but not limited to, pursuant to grantback licenses from Licensees, during the Term of this Agreement. 

        1.24.    "PER.C6
Patents" shall mean any and all Patents that claim PER.C6 Cells for use within the Field. Schedule 1.24 sets forth a
non-exhaustive list of the PER.C6 Patents and shall be diligently updated by the parties as appropriate. 

        1.25.    "Products"
shall mean bulk products and/or finished pharmaceutical compositions intended for diagnostic and/or therapeutic purposes, and administration
to humans, and which are manufactured, marketed, sold and/or distributed within the Field. 

        1.26.    "Regulatory
Approval" shall mean all official approvals by government, pricing or health authorities in a country or supra-national authority having the
force of law in a country or 

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countries (such as the European Medical Evaluation Authority or any successor agency) which are required for the use, sale, importation, manufacture, packaging, labeling, promotion and, if required,
pricing and reimbursement, of pharmaceutical or biopharmaceutical products in any country of the Territory. 

        1.27.    "Term"
shall mean the term of this Agreement as more specifically provided by the provisions of Section 9 hereof. 

        1.28.    "Territory"
shall mean the entire world. 

        2.    Development Program.    

        2.1.  Each
of DSM and Crucell shall execute the respective tasks and activities of a program of research and development directed to the commercialization of Crucell
Technology as a manufacturing platform and the commercial-scale production of Products utilizing Crucell Technology as the development and manufacturing platform in the Field. The development program
(the "Development Program") shall be undertaken in accordance with the development plan (the "Development Plan") annexed hereto as Schedule 2.1 and which may be updated and amended periodically
in accordance with the mutual agreement of the parties. The Development Plan also includes a budget and schedule of labor contribution, other internal and/or external expenditures, capital
improvements and investments believed necessary to achieve the objectives of the Development Program and assigns the activities to be undertaken by the parties respectively. The Development Plan shall
be executed by the parties according to the budget contained therein. In case DSM would not have fermentation capacity at a (minimum) scale of    •    liters
available (in time), as planned according to the Development Plan, parties will discuss in good faith a resolution, whereby a possible option would be to have such work performed by a third party. All
costs associated with the Development Program shall be shared on the basis of a    •    sharing by each party. This shall apply to both the internal contribution at
commercial rates and external expenditures according to the budget as agreed by the Development Committee. The Development Plan contemplates, as of the date hereof, that each party's annual aggregate
contribution will not exceed a monetary value of €    •    (    •    Euro) annually and can be provided in cash or in
kind. In kind, in relation to Crucell, shall mean FTE's at a stipulated annual cost of Euro    •    . In kind, in relation to DSM, shall mean FTE's and/or occupancy,
to be calculated at commercial rates and differentiating between employees, locations and occupied capacity. Commercial rates shall mean the rate at which such employees and capacity are then
generally charged to third party customers of DSM. Crucell is entitled to have an independent auditor, reasonably acceptable to DSM, verify the correctness of the commercial rates as calculated by DSM
in connection with the Development Program. It is understood by the parties that DSM shall perform at least    •    % of the activities under the Development Program.
Neither party shall be obligated to incur costs, make or incur contributions or otherwise invest in or perform development activities in connection with the Development Program in excess of the
budgeted amounts for such party set forth in the Development Plan, subject only to the obligation of good faith negotiation set forth in Section 2.4. Further, the parties agree that the costs
to develop or expand production facilities shall not be deemed a shared cost of the Development Program, except to the extent such costs to develop or expand production facilities have been agreed in
the budget of the Development Plan and to the extent of the actual use of capacity for the Development Program, allocated and amortized in accordance with commercial rates and in a manner consistent
with such party's standard cost accounting practices consistently applied. 

        2.2.  Within
30 days of the date of signature of this Agreement, the parties shall establish a joint development committee (the "Development Committee") composed of an
equal number of representatives designated by each of Crucell and DSM, respectively. The overall number of representatives on the Development Committee shall be determined by agreement of the parties 

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from time to time. Development Committee members shall have appropriate expertise in PER.C6 Know-How or mammalian biopharmaceutical development and manufacturing technology generally. In
addition, at least one member of the Development Committee designated by each party shall have executive level authority on behalf of such party and at least one member shall have a commercial
position. Decisions of the Development Committee shall be by majority determination, whereby all members shall be present or duly represented. The Development Committee shall meet in person and by
telephonic communication as needed, and at least once per quarter, to review the status and progress of the Development Program. Each party agrees to make such technical, scientific or other personnel
available for consultation with the Development Committee as the Development Committee may from time to time reasonably request. 

        2.3.  The
responsibilities of the Development Committee shall include (i) monitoring the progress of the Development Program, (ii) reviewing the achievement of
the Development Milestones in light of the progress or results of the Development Program, including, without limitation, performing the evaluations and determinations required to recommend to the
parties the adjustment of a Development Milestone or, (iii) evaluating and recommending modifications to the Development Plan, including, without limitation, the budget for contributions and
expenditures and the establishment and modification of Development Milestones from time to time, (iv) evaluating and recommending the continuation or discontinuation of the Development Program
or any portion thereof, and (v) monitoring publications and other disclosures of technology developed during the course of the Development Program. The Development Committee shall not be
entitled to adjust the Development Milestones or Targets, but, if appropriate, shall make recommendations to the parties as to such possible adjustment. The Chief Executive Officer of DSM and the
Chief Executive Officer of Crucell shall in such case decide in good faith upon a possible adjustment, based upon such recommendations of the Development Committee. The parties agree to consider and
negotiate in good faith, in light of the development and commercial objectives of this Agreement and the status of the Development Program from time to time, any increases in the budget included in
the Development Plan recommended by the Development Committee. At least 3 months prior to the end of each Development Year (as hereinafter defined) during the Term, the Development Committee
shall make a recommendation to the parties as to the continuation of the Development Program and the modification of any Development Milestone and shall inform the parties as to the achievement status
of each Development Milestone. In the event the Development Committee is unable to agree upon a material component of the Development Plan, any proposed modification thereof or actions to be taken by
either party to fulfill the objectives of any component thereof, including modifications to Development Milestones or whether or not specific Development Milestones have been achieved, the matter
shall be referred to the Chief Executive Officer of each party for resolution. If and to the extent deemed useful by the Chief Executive Officers of the parties, they may decide to appoint an
independent expert to give a binding or non-binding (as to be agreed upon by the Chief Executive Officers) advice on any technical aspects of the issue under dispute. In the event such
officers are unable to agree upon a resolution within 90 days of such referral, which term may be extended by the parties in mutual consent, either party shall be entitled to submit the matter
for resolution by arbitration in accordance with Section 10.2 hereof. 

        2.4.  Each
of DSM and Crucell shall maintain records of their respective activities under the Development Program in sufficient detail and in good scientific manner as will
accurately reflect all work done and results achieved in the performance thereof (including the maintenance of data in such form as may be required by Regulatory Authorities). Each party shall permit
the other, upon reasonable advance notice, access to all such materials and data during the Term solely for purposes related to the objectives of this Agreement. 

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        2.5.  In
light of the uncertainties inherent to research and development activities of the type contemplated by this Agreement, neither party shall be deemed to represent to
the other as to the success of the Development Program, the achievement of any Development Milestone, or as to the successful development, Regulatory Approval or marketing of Products which utilize
the PER.C6 Cell platform. In addition, it has been agreed that Crucell shall continue to develop the Crucell Technology also outside of the Development Program. 

        3.    License Grants; Technology Transfer.    

        3.1.  For
purposes of this collaboration between Crucell and DSM and its objectives, the furtherance of the Development Program and in order to facilitate the research and
commercial objectives thereof, Crucell hereby grants to DSM under the Crucell Technology an exclusive, royalty-free (notwithstanding the payments required by Sections 5.1 and 5.3)
perpetual license (the "DSM License") with the right to sublicense to third parties, for the research, development and manufacture of Products in the Field solely on behalf of Licensees. The DSM
License shall be subject to modification in accordance with the further terms and conditions hereof. The DSM License granted hereby shall apply throughout the Territory and shall be deemed to permit
the performance of research and development services and the manufacture, transfer and sale by DSM of Products to Licensees throughout the Territory (i) for clinical study or other research
purposes, to the extent such Licensee has a Research License or a Commercial License and (ii) for commercial sale and distribution, to the extent such Licensee has a Commercial License. 

        3.2.  Subject
to the further terms and conditions hereof, the DSM License shall include a right to conclude MTA's (as such term is defined in Section 1.17) and to
grant Research Licenses and Commercial Licenses to third parties (such component of the DSM License being referred to herein as the "DSM Sublicense"). Crucell shall not, during the term of this
Agreement and thereafter, grant any such right to grant Research Licenses and Commercial Licenses to third parties, to any third party without DSM's express prior written consent. 

        3.3.  Notwithstanding
the exclusive nature of the DSM License, the terms and conditions of any Research License or Commercial License which Crucell offers or enters into with
any Licensee, or had entered into prior to the date of execution of this Agreement (which Research and Commercial Licensees are identified on Schedule 3.3 hereto), shall not be deemed to
violate the exclusive nature of the DSM License to the extent such terms or conditions are required for the development, captive manufacture, testing, regulatory approval or commercialization of its
Own Products by such Licensee, acting for its own account and not as manufacturer for any unaffiliated third party and further provided that any such Research or Commercial License hereafter entered
into by Crucell complies with the template set forth in Schedule 4.3. 

        3.4.  As
additional consideration for the DSM License and in furtherance of the research and commercial objectives of the Development Program, DSM hereby agrees to grant
Crucell a royalty-free, non-exclusive perpetual license within the Field (the "Grantback License"), with the right to sublicense
within the Field, under Patents filed by DSM relating specifically to Crucell Technology, resulting from the Development Program. 

        3.5.  In
addition to the provisions above set forth with respect to the DSM License, the DSM License shall be deemed to include a perpetual, non exclusive license to DSM and
its Affiliates, without the right to sublicense, to perform research and development activities with respect to Crucell Technology for use in the development of Products for DSM or its Affiliates' own
account, which license shall have the terms and conditions set forth in the template for Research Licenses to be agreed upon by the parties pursuant to Section 4.3 hereof but without regard to
the payments of royalties or other consideration therein contained. No separate consideration shall be payable by DSM or its Affiliates to Crucell in respect of such license. The grantback license set
forth in the template for Research Licenses, shall be substituted by the grantback clause as 

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described in Section 3.4 of this Agreement. However, in such case the requirement pertaining to Patents "resulting from the Development Program" shall not apply. Notwithstanding any existing
rights under the grantback licenses of Sections 3.4 and 3.5, which shall remain in effect, in case of completion of the Development Program, the obligation to grant a grantback license shall cease
with immediate effect with respect to Patents filed for results obtained after the completion of the Development Program. If the Development Program is terminated by DSM pursuant to Sections 9.2 or
9.4 prior to the completion thereof, the obligation to grant a grantback license shall cease with immediate effect with respect to Patents filed for results obtained after the date of termination by
DSM. If the Development Program is terminated for any other reason the obligation to grant a grantback license with respect to Patents filed for results obtained after the termination of the
Development Program shall cease 12 months after the date of termination. 

        3.6.  In
furtherance of the DSM License and the objectives of the Development Program, Crucell will make available at the facilities of DSM (and, upon DSM's reasonable
request and upon reasonable advance notice, at the facilities of DSM's customers, but only to the extent within the scope of the DSM License), from time to time as mutually agreed, such scientific and
technical personnel as may be required to fully convey the Crucell Technology to DSM or such customers. The Development Plan sets forth the parties' current understanding as to the steps believed to
be necessary to effect the transfer of the Crucell Technology to DSM. 

        3.7.  Each
party agrees to provide to the other and to Licensees such rights of reference to regulatory filings (including drug master files and biologic master files) and to
establish, maintain and supplement such drug and biologic master files containing Crucell Technology, DSM Technology or Joint Technology, as the case may be, in order to facilitate the obtaining and
maintenance of Regulatory Approvals with respect to Products by either party or by Licensees. Such rights of reference shall survive the expiration or termination of this Agreement for such period as
the party requiring any such right of reference continues to possess rights to develop, license or manufacture Products within the Field. 

        3.8.  For
purposes of this Agreement, each party's technology transfer obligations as specifically mentioned in this Agreement shall be deemed to require the provision by
such party of such
information and assistance, including both trade secrets as well as information in the public domain, as would reasonably be required to permit an experienced and technologically-sophisticated
recipient of such technology transfer to be able to practice the subject technology. 

        3.9.  At
the date of signature of this Agreement Crucell has not performed and is not performing research activities to explore technology for commercialization in the Field,
that is not covered in the Crucell Technology definition of this Agreement. In case Crucell would, during the time the DSM License is exclusive, generate any new ideas, inventions, improvements,
know-how or patents within the Field of production of proteins, including, but not limited to, monoclonal antibodies and polypeptides, and conjugates thereof, for the development,
manufacture, sale, use and distribution of Products and which new technology is not covered by the definition of Crucell Technology, Crucell shall, during the Development Program, refrain from
commercializing such new technology in a way that competes with the Crucell Technology. However, in case Crucell decides to initiate research activities to explore technology for commercialization in
the Field after the date of signature of this Agreement, it shall so notify DSM. If, after the Termination of the Development Program Crucell elects to commercialize such new technology, Crucell shall
so notify DSM and DSM shall have the first right and exclusive right to negotiate with Crucell for a period of six (6) months, including a period of two (2) month to perform a due
diligence on such new technology, on a possible collaboration with respect to such new technology. In such case both parties shall negotiate in good faith any such potential collaboration. 

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        4.    Commercialization.    

        4.1.  It
is the intention of the parties that DSM will utilize the Joint Technology, the Crucell Technology and DSM Technology, to offer Product development and manufacturing
services to Licensees with respect to Products on such terms and conditions as DSM may determine to offer. DSM shall be solely responsible for such development and manufacturing services. DSM shall be
entitled to market and promote the availability of its development and manufacturing services to third parties. 

        4.2.  Crucell
shall ensure that Licensees and potential Licensees who contact Crucell and are seeking development, clinical manufacture and/or commercial manufacturing
services on the PER.C6 Cell platform are being referred solely to DSM as long as the DSM License remains exclusive, provided that, nothing contained herein shall be deemed to restrict or limit
Crucell's right to provide clone generation and small scale (at a    •    scale or less) production services to Licensees for research purposes only or, at any time
that the DSM License is non-exclusive, to authorize or license third parties to do so; provided further, however, that Crucell shall not advertise the provision of or solicit manufacturing
services by Crucell for Products on the Crucell Technology platform provided that, nothing contained herein shall be deemed to restrict or limit Crucell's right to advertise the provision of or
solicit clone generation and small scale (at a    •    scale or less) production services to Licensees for research purposes only. In addition, the template for
Research Licenses and Commercial Licenses included in Schedule 4.3 will require Licensees seeking external process development, clinical material production or commercial contract manufacturing
to obtain such services from DSM. 

        4.3.  The
parties shall, within 30 days of the date of signature of this Agreement, agree upon a summary of the basic terms and conditions pursuant to which Crucell
and DSM will offer Research Licenses and Commercial Licenses to potential Licensees, based upon the drafts attached hereto in Schedule 4.3. Within 30 days from the date of signature of
this Agreement, the parties shall form a committee (the "Business Development Committee") to develop and manage a business development program for the establishment of Licensees. The Business
Development Committee shall be composed of an equal number of representatives of each party, with each party retaining the right to change its designees from time to time. The Business Development
Committee shall meet at least once per month, in person or by telephonic conference, or at such other intervals as the parties may agree. Each party agrees to make such of its personnel available for
consultation with the Business Development Committee as such Committee may from time to time reasonably require. Any decision of the Business Development Committee shall be a majority determination,
whereby all members shall be present or duly represented. Responsibilities of the Business Development Committee shall include, without limitation, monitoring and reviewing the commercial Milestones,
monitoring, collecting and sharing market information related to the Field, reviewing and monitoring the progress of the offering and concluding of Research Licenses and Commercial Licenses and
evaluating and sharing suggestions for license negotiation strategies and the overall marketing strategy, including, with respect to specific license negotiations. Any material deviations by either
party from the terms and conditions agreed upon by the Parties will require approval of the Business Development Committee. In addition, neither party shall have the right, and shall not hold itself
out to third parties as having the right, to negotiate the terms of, or bind contractually, the other party to any license, manufacturing or other contract, agreement, arrangement or understanding. 

        4.4.  Notwithstanding
the provisions of Section 4.3, either party, when offering a Research or Commercial License, may determine, at its sole discretion, to reduce or
increase the milestone payments, license fees or royalties payable to it to less than the levels set forth in Schedule 4.3 or otherwise determined by the Business Development Committee;
provided that (i) any such reduction so determined by one party shall be disregarded by such party in determining Crucell 

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Collaboration Revenue or DSM Collaboration Revenue, as the case may be (i.e., such revenue will be recalculated based on the template formulae applicable to the relevant sales as to which such
reduction was implemented) and (ii) any increase of milestone payments shall be shared equally by the parties. It is further agreed that if and to the extent any Research or Commercial Licenses
granted by Crucell prior to the date of signing of this Agreement contain any most favored nations clauses or similar arrangements as a consequence of which the licensing revenues from such agreements
may be reduced as a consequence of future lower licensing revenues charged to third parties, such lower licensing revenues shall be born by each DSM and Crucell equally. Schedule 4.4. contains
a list of those Licenses which might be subject to most favored nations clause consequences. For avoidance of doubt and greater certainty each DSM and Crucell agree not to grant any Research or
Commercial Licenses which contain any most favored nations clauses or similar arrangements after signing of this Agreement. 

        5.    Consideration for Crucell Technology; Collaboration Revenues.    

        5.1.  As
consideration for the DSM Share granted to DSM hereunder, DSM agrees to make the following payments to Crucell: 

        5.1.1.        •     million
Euros within 10 days following the date of signature of this Agreement; 

        5.1.2.        •     million
Euros within 30 days following the date (i) the First Development Milestone has
been achieved, or (ii) which is the first anniversary of the date of signature, whichever is later. 

        5.1.3.        •     million
Euros within 30 days following the date (i) the Second Development Milestone has
been achieved, or (ii) which is twelve months following the date required for the payment required by Section 5.1.2 or 5.1.7, whichever (i) or (ii) is later. 

        5.1.4.        •     million
Euros within 30 days following the date (i) the Third Development Milestone has
been achieved, or (ii) which is twelve months following the date required for the payment required by Section 5.1.3 or 5.1.7, whichever (i) or (ii) is later. 

        5.1.5.        •     million
Euros within 30 days following the date of FDA approval of the first Product covered by
this Agreement. 

        5.1.6.    Development
Milestones for each of the first three consecutive 12 month periods (each such period a "Development Year" and the last day of each
such period a "Target Date") from and after the date of last signature of this Agreement (respectively, the "First", "Second" and "Third" Development Milestones) shall be as set forth in the
Development Plan, subject to adjustment from time to time by the parties. In the event a Development Milestone is achieved prior to its original Target Date, the Target Date for the next succeeding
Development Milestone shall be deemed amended to refer to the date which is 12 months from the completion of such immediately preceding Development Milestone. 

        5.1.7.    In
the event a Development Milestone has not been achieved by its respective Target Date as decided by the Development Committee, the Development
Committee shall have the option, to specify a deferred Target Date for such Development Milestone to a date which is no more than nine months following the original Target Date. In the event the
Development Committee has exercised such option, DSM's obligation to make the payment required by Section 5.1 associated with the achievement of such Development Milestone shall be deferred
until the relevant Development Milestone has been achieved; provided, however, in the event such Development Milestone has not been achieved by such deferred Target Date, as decided by the Development
Committee, the Development Committee shall issue a report to the Chief Executive Officers of the parties, indicating the status of the Development 

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Milestones and the reasons for not achieving such Development Milestone. Within 30 days following the issuance of such report, during which period the Chief Executive Officers of the parties
shall consult each other in good faith, DSM shall either make the payment required by Section 5.1 associated with the achievement of such Development Milestone or not, in which latter case
(i) the DSM Share shall be subject to reduction in accordance with Section 9.6.2 from and after the deferred Target Date unless DSM nevertheless elects to pay the corresponding
Section 5.1 payment and (ii) unless DSM so elects nevertheless to pay the corresponding Section 5.1 payment in respect of such Development Target within 30 days following
such deferred Target Date, the DSM License shall, upon written notification by Crucell, automatically be converted into a non-exclusive license. 

        5.1.8.    Each
of the payments provided by this Section shall be deemed fully-earned and non-refundable as of the time of payment and shall not be
credited against any other obligation of DSM hereunder. 

        5.2.  As
consideration for the rights granted to Crucell hereunder, Crucell agrees to pay DSM an amount equal to    •    % of Crucell
Collaboration Revenues (the "DSM Share"). Payment of the DSM Share shall be made quarterly, no later than 30 days following the end of each calendar quarter. Payments shall be made in Euros
and, to the extent Crucell Collaboration Revenues were paid to Crucell in any currency other than Euros, shall be converted to Euros at the rates of exchange prevailing at the time of receipt of such
Crucell Collaboration Revenues by Crucell. 

        5.3.  In
light of the objectives of the collaboration contemplated hereby, DSM agrees that Crucell shall be entitled to    •    % of all DSM
Collaboration Revenues. DSM shall make payments to Crucell of amounts due pursuant to this Section quarterly and the parties agree that the reciprocals of the provisions of Sections 5.2 and 5.5 (i.e.,
Crucell having the rights of audit therein provided with respect to DSM) shall apply in favor of Crucell to the accounting for and making of such payments and recordkeeping and rights of inspection
with respect thereof. 

        5.4.  Crucell
shall maintain true and complete books and records which accurately reflect Collaboration Revenues at the principal executive offices of Crucell for a period of
at least 5 years from the end of the year in which such Crucell Collaboration Revenues were recognized. Together with each payment of the DSM Share, Crucell shall provide a report which sets
forth the Crucell Collaboration Revenues for the year as to which such payment relates with reasonable specificity. DSM shall have the right to inspect and audit such books and records required to be
maintained by Crucell, including by the use of independent certified public accountants to which Crucell shall have no reasonable objection, solely for the purpose, and to the extent necessary, to
verify the DSM Share for any period covered thereby. Any such audit shall be conducted on reasonable advance notice no more than once per year, shall be conducted in a manner which does not
unreasonably interfere with Crucell's operations and shall be subject to the confidentiality provisions hereof, subject only to the right of disclosure in any legal proceeding hereunder, but only to
the extent reasonably required to resolve any bona fide dispute arising hereunder. Such audit shall be at the sole expense of DSM;  provided that in the
event any such audit reveals that the DSM Share for any period has been underpaid by 5% or more, which underpayment is not then
subject to a bona fide dispute by Crucell being diligently pursued in good faith, Crucell will be responsible for the costs of such audit, as well as
the amount of such underpayment. Any overpayment or underpayment identified by such audit shall be corrected by the Parties as soon as possible. 

        5.5.  Each
party shall maintain true and complete books and records which accurately reflect the contributions, expenditures and the like required to be made by such party.
The other party shall have the right to inspect and audit such books and records, including by the use of independent certified public accountants to which the record-keeping party shall have no 

10

 

reasonable objection, solely for the purpose, and to the extent necessary, to confirm the making of the contributions required by the Development Plan. Any such audit shall be conducted on reasonable
advance notice no more than once per year, shall be conducted in a manner which does not unreasonably interfere with the record-keeping party's operations and shall be subject to the confidentiality
obligations hereof, subject only to the right of disclosure in any legal proceeding hereunder, but only to the extent reasonably required to resolve any bona
fide dispute arising hereunder. Such audit shall be at the sole expense of the party conducting the audit; provided that in the
event any such audit reveals that the contributions for any period have been underfunded by 5% or more, which underfunding is not then subject to a bona
fide dispute by the record-keeping party being diligently pursued in good faith, the record-keeping party will be responsible for the costs of such audit, as well as the cure
of the underfunding. Any overpayment or underpayment identified by such audit shall be corrected by the Parties as soon as possible. 

        5.6.  Each
party shall maintain true and complete records of all Research Licenses and Commercial Licenses entered into by such party. All such records shall be available for
inspection and review by external and independent legal counsel to which the party subject to such review has no reasonable objection no more than once per calendar year, and upon reasonable advance
notice, solely for purposes of verifying compliance with the standards for such agreements set forth herein. 

        6.    Intellectual Property.    

        6.1.  The
inventorship of ideas, improvements and/or inventions conceived or reduced to practice in the course of the Development Program shall be determined in accordance
with the patent and other intellectual property laws of the country where such invention was so conceived or reduced to practice. Notwithstanding the foregoing, each of the parties shall have an equal
undivided interest and beneficial ownership in all such inventions which are Joint Technology and the parties agree to execute and deliver such documents or instruments as may reasonably be required
to confirm or perfect each party's interest and beneficial ownership in any such Joint Technology. 

        6.2.  Each
party agrees to use its commercially reasonable efforts, at its sole expense, or, if appropriate, at its joint expense, to prepare, file, prosecute and maintain
Patents throughout the Territory, in such countries as it may be commercially reasonable to do so, representing inventions owned by such party and included in Crucell Technology or Joint Technology,
as the case may be. Notwithstanding the preceding, in the event either party declines to file, or, having filed, declines to further prosecute or maintain any Patent, the other party shall have the
right to file, prosecute and maintain the necessary Patent, at its sole expense and in its own name. Notwithstanding any other terms or conditions of this Agreement, each party shall be deemed to have
a fully paid, non-exclusive license, with the right of
sublicense, to any such technology developed by such party but as to which such party declines to file, or, having filed, declines to further prosecute or maintain any Patent and the other party has
elected to file and prosecute a Patent in accordance with the preceding sentence. It is understood by the parties that in case either party reasonably requests any part of the Joint Technology to be
treated as proprietary Know-How, such request shall be discussed in good faith and shall not be treated as a declination to file a Patent as described in this Section 6.2. 

        6.3.  Each
of Crucell and DSM shall keep the other reasonably informed, through the Development Committee, as to the status of Patent matters and inventions, including,
without limiting the generality of the foregoing, by allowing the other party a reasonable opportunity to review and comment upon proposed Patent filings and all correspondence received from any
patent office or other governmental entity or third party with respect thereto. 

11

 

        6.4.  In
the event the production, sale or use of any Product results in a claim, suit or proceeding in the nature of patent or other intellectual property infringement
against Crucell or DSM relating to Crucell Technology, DSM Technology or Joint Technology, the party receiving notice of such claim shall promptly notify the other party in writing setting forth a
description of the claim in reasonable detail. Each party shall have the right, but not the obligation, to defend and control the defense of such claim with counsel of its choice to which the other
party shall have no reasonable objection. Such other party shall provide such reasonable cooperation in the defense of any such claim as the relevant party may reasonably request. In the event a party
does not promptly notify the other party of its intention to defend any such claim, the other party shall have the right, but not the obligation, to assume and control such defense with counsel of its
choice to which the relevant party has no reasonable objection. In addition, irrespective of which party has initially undertaken the defense of any such matter, the other party shall have the right,
exercised by furnishing written notice within 6 months of the commencement of any such suit or proceeding to the party undertaking such defense, to participate in the defense of such matter,
provided that such party agrees to be responsible for    •    % of the internal and out-of-pocket expenses of such defense, including costs
incurred prior to the exercise by such party of its right to so participate. 

        6.5.  In
the event that either party becomes aware that any Crucell Technology, DSM Technology or Joint Technology necessary for the development, manufacture, use or sale of
Products is infringed or misappropriated by a third party, such party shall promptly notify the other party. With respect to Crucell Technology and Joint Technology Crucell shall have the first
option, but not the obligation, to enforce the rights represented by the Crucell Technology or Joint Technology, as the case may be, in its own name. In the event Crucell declines to initiate suit
within 180 days of the receipt by or furnishing to Crucell of notice of the alleged infringement, DSM may initiate such suit in its own name or the name of Crucell. The party prosecuting the
infringement shall keep the other party reasonably informed as to the progress of such proceeding. In addition, irrespective of which party has initially undertaken the prosecution of any such matter,
the other party shall have the right, exercised by furnishing written notice within 6 months of the commencement of any such suit or proceeding to the party undertaking such prosecution, to
participate in the prosecution of such matter, provided that such party agrees to be responsible for    •    % of the internal and
out-of-pocket expenses of such prosecution, including costs incurred prior to the exercise by such party of its right to so participate. 

        6.6.  The
party assuming the defense or prosecution of any intellectual property matter covered by this Section shall be solely responsible for the costs incurred in
connection therewith and shall have the sole right to the proceeds of any recovery or judgment obtained, as the case may be. In the event the other party has exercised its option to participate in any
such defense or prosecution, each party shall be responsible for    •    % of internal and out-of-pocket expenses thereof and shall be entitled
to    •    % of the benefits of any recovery or judgment. Each party shall be solely responsible for its internal costs of participating in any such matter. 

        6.7.  Neither
party shall enter into any settlement or compromise of any matter being defended or prosecuted pursuant to this Section 6 which admits or concedes that
any DSM Technology, Crucell Technology or Joint Technology is invalid, infringing third party intellectual property rights, inherently defective or unenforceable without the prior written consent of
the other party. 

12

  

        6.8.  Each
party agrees that it will not assert any claim of invalidity or patent infringement against the other with respect to any Joint Technology or technology which is
included (or becomes included) in the DSM License or Grantback License. 

        7.    Representations, Warranties and Indemnification.    

        7.1.  Each
party represents and warrants to the other that (i) it has the full right and authority to enter into this Agreement, grant the rights and licenses granted
herein and perform each of its other obligations hereunder; (ii) this Agreement has been duly authorized and approved by all necessary corporate action on the part of such party;
(iii) it has not previously granted, and will not grant, any rights in conflict with the rights and licenses granted herein; and (iv) there are no existing or threatened actions, suits
or claims pending against it with respect to Crucell Technology or DSM Technology or its right to enter into and perform its obligations under this Agreement which would restrict, interfere with or
impose any costs, obligations, liens or encumbrances in respect of the rights granted to either party hereunder. 

        7.2.  Crucell
furthermore warrants and represents that (i) it has full and unrestricted ownership of the Crucell Technology and, except as disclosed in
Schedule 7.2, that it has not granted any rights to third parties that may interfere with or violate the provisions and purposes of this Agreement (ii) there are no facts or
circumstances known to Crucell on the date of signing this Agreement which could potentially interfere with or otherwise detrimentally affect the full enjoyment by DSM of the rights granted to it
under this Agreement or the achievement of the purposes set forth herein and (iii) to the best of its knowledge at the date of signature of this Agreement the Crucell Technology as licensed by
Crucell to DSM hereunder with the purpose to establish an expression platform and to perform the activities contemplated in the Development Program do not infringe third party intellectual property
rights. For the avoidance of doubt, it is understood by the parties that the aforementioned representation and warranty under (iii) does not apply to the extent of (a) activities
performed by DSM under the Development Program in as far as using technology other than the Crucell Technology, (b) activities not falling under the Development Program and/or
(c) manufacturing activities. 

        7.3.  DSM
and Crucell specifically disclaim any representation or warranty that the Development Program will be successful, in whole or in part. The failure of the Parties to
successfully develop improvements to Crucell Technology or DSM Technology or the application thereof to the research or manufacture of Products will not constitute a breach of any representation or
warranty or other obligation under this Agreement. EXCEPT FOR WARRANTIES PROVIDED FOR IN THIS AGREEMENT, DSM AND CRUCELL EXPRESSLY DISCLAIM ANY WARRANTIES OR CONDITIONS, EXPRESS, IMPLIED, STATUTORY OR
OTHERWISE, WITH RESPECT TO THE
DEVELOPMENT PROGRAM AND THE DSM TECHNOLOGY AND CRUCELL TECHNOLOGY, INCLUDING, WITHOUT LIMITATION, ANY WARRANTY OF MERCHANTABILITY, NON-INFRINGEMENT, FITNESS FOR A PARTICULAR PURPOSE OR
VALIDITY. 

        7.4.  Each
party (the "Indemnifying Party") shall indemnify the other and its Affiliates and their respective directors, officers, employees and agents and the successors and
assigns of any of the foregoing (the "Indemnitees") and protect, defend, save and hold each Indemnitee harmless from and against any and all liabilities, damages, losses, settlements, claims, actions,
suits, penalties, fines, costs or expenses (including, without limitation, reasonable attorneys' fees and other expenses of litigation) (each of the foregoing, a "Claim") incurred by any Indemnitee,
arising from or occurring as a result of the breach of any representation or warranty of the Indemnifying 

13

 

Party made herein. Each Party's indemnification obligation under the previous sentence shall be limited to an amount equal to    •    Million Euro in the aggregate.
In addition: 

        7.4.1.    Crucell
shall indemnify DSM and its Affiliates and hold DSM and its Affiliates harmless from and against Claims to the extent directly arising from
PER.C6 Cells or Crucell Technology. Notwithstanding the foregoing, Crucell's indemnification obligation pursuant to the previous sentence shall be limited to an amount equal to
    •     million Euros in the aggregate, provided that the foregoing limitation shall not apply in the event Crucell is judicially determined to have acted with
gross negligence or willful misconduct in respect of a Claim as to which indemnification is sought. 

        7.5.  A
party (the "Indemnitee") that intends to claim indemnification under this Section shall promptly notify the other party (the "Indemnitor") in writing of any loss,
claim, damage, liability or action in respect of which the Indemnitee or any of its Affiliates or their respective directors, officers, employees or agents intend to claim such indemnification, and
the Indemnitor shall have the right to participate in, and, to the extent Indemnitor so desires, to assume the defense thereof with counsel of its choice to which the Indemnitee shall have no
reasonable objection. In addition, the Indemnitee shall have the right to participate in, but not control, the defense of any Claim with counsel of its choice at its own expense. The indemnity
provided by this Section shall not apply to amounts paid in settlement of any Claim if such settlement is effected without the consent of the Indemnitor, which consent shall not be unreasonably
withheld. The failure to deliver written notice to the Indemnitor within a reasonable time after becoming aware of a Claim, if prejudicial to its ability to defend such action, shall relieve such
Indemnitor of any liability to the Indemnitee under this Section with respect to such Claim. The Indemnitee under this Section, including its employees and agents, shall cooperate fully with the
Indemnitor and its legal representatives in the investigation and defense of any action, claim or liability covered by this Indemnification. 

        7.6.  Each
party shall use all commercially reasonable efforts to maintain liability insurance with respect to its activities and liabilities hereunder or contemplated
hereby. Such insurance shall be in such amounts and subject to such deductibles as the parties may agree, based on standards prevailing in the industry from time to time. 

        8.    Confidentiality.    

        8.1.  Except
as expressly provided herein, the parties agree that, for the Term of this Agreement and for seven (7) years thereafter, the receiving party shall keep
completely confidential and shall not publish or otherwise disclose, and shall not use for any purpose, other than as contemplated by this Agreement and the rights granted thereunder, any information
furnished to it by the other party hereto pursuant to this Agreement. The foregoing shall not be deemed to apply to information which such party can establish by competent proof: 

        8.1.1.    was
already known to the receiving party, other than under an obligation of confidentiality, at the time of disclosure; 

        8.1.2.    was
generally available to the public or otherwise part of the public domain at the time of its disclosure to the receiving party; 

        8.1.3.    became
generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the
receiving party in breach of this Agreement; or 

        8.1.4.    was
subsequently lawfully disclosed to the receiving party without obligation of secrecy and non-use by a person other than a party or
developed by the receiving party without reference to any information or materials disclosed by the disclosing party. 

14

 

        8.2.  Each
party hereto may disclose information required to be maintained as confidential hereunder to the extent, and only to the extent, such disclosure is reasonably
necessary in (i) filing or prosecuting Patent applications as permitted under this Agreement, (ii) prosecuting or defending litigation, (iii) complying with applicable
governmental regulations or otherwise submitting information to tax or other governmental authorities, (iv) making a permitted (sub)license or other exercise of its rights hereunder,
(v) conducting pre-clinical or clinical trials, or (vi) providing all necessary information required for a fair scientific and economic assessment of market value to a
potential permitted (sub)licensee or assignee of rights hereunder or customer of either party; provided that if a party seeks to make any such disclosure of Confidential Information, pursuant to a
confidentiality agreement which provides for confidential treatment to substantially the same extent as required hereby, it will give reasonable advance notice to the other party of such intended
disclosure and, save to the extent inappropriate in the case of Patent applications, will use its best efforts to secure confidential treatment and appropriate limitations of such information prior to
its disclosure (whether through protective orders or otherwise). 

        9.    Term and Termination    

        9.1  This
Agreement shall become effective as of the Effective Date and, unless sooner terminated in accordance with the terms hereof, shall be deemed to continue for such
indefinite period until terminated in accordance with its provisions (the "Term"). During any period that the DSM License remains in effect pursuant to this Section, Crucell shall continue to pay DSM
the DSM Share, DSM shall continue to pay Crucell the amounts required by Section 5.4 and the terms and conditions of this Agreement shall continue to apply and remain in effect throughout any
such period. 

        9.2  Either
party may terminate this Agreement in the event the other party shall have materially breached or defaulted in the performance of any of its material obligations
hereunder, and such default shall have continued for 60 days after written notice thereof, describing such breach or default with reasonable specificity, was provided to the breaching party by
the non-breaching party. Any such termination shall become effective at the end of such 60 day period unless the breaching party has cured such breach or default during such period
to the reasonable satisfaction of the non-breaching party or, if such breach is susceptible of cure but not within a 60 day period, has commenced and is diligently pursuing such
cure in a manner which reasonably assures its timely completion. Notwithstanding the generality of the foregoing it is agreed that in case DSM notifies Crucell that it will invoke its right under
Section 9.5.2 Crucell shall be awarded a 120 day extension of the remedy period. 

        9.3  DSM
shall have the option to terminate this Agreement at any time without cause, effective upon 60 days written notice to the other party. 

        9.4  This
Agreement can be terminated by a party in the event the other party files a petition under any bankruptcy, insolvency, moratorium or similar law for the protection
of debtors, or has any such petition filed against it, which petition is not dismissed within 45 days. Notwithstanding the foregoing, termination of the Agreement pursuant to this Section shall
not be deemed to terminate the DSM License, or the obligations of payment of the respective Shares, which shall continue to apply as set forth and adjusted pursuant to Section 9.5. 

        9.5  Regardless
of the cause for termination, termination or expiration of this Agreement shall in no event affect the DSM License, the Sublicense or the Grantback License,
except to the extent specifically provided for in this Section 9.5. 

        9.5.1    Only
in case of termination of this Agreement by Crucell pursuant to Section 9.2 or 9.4 or by DSM pursuant to Section 9.3, the DSM License
shall turn into a non exclusive 

15

 

license and the DSM Share shall be adjusted to the Residual Share (as defined in Section 9.6 below). 

        9.5.2    In
case of termination of this Agreement by DSM pursuant to Section 9.2 or 9.4 (provided such bankruptcy has become final as to Crucell), Crucell
shall be obligated to take all steps necessary to assign and convey to DSM legal title to the Patents included in the DSM License and described in Schedule 9.5.2. hereto. In case of termination
of this Agreement by DSM pursuant to Section 9.2 and consequently legal title transfer to the Patents from Crucell to DSM described in Schedule 9.5.2. hereto has occurred, Crucell shall
receive a non-exclusive, perpetual, royalty free, fully paid up license to those Patents from DSM, without the right to sub-license. 

        9.6  In
case of termination of this Agreement by Crucell pursuant to Section 9.2 or 9.4 or by DSM pursuant to Section 9.3, DSM shall continue to be entitled to
receive the DSM Share, as adjusted in accordance with the following provisions (as so adjusted, the "Residual Share"), for the period and subject to the terms and conditions set forth below: 

        9.6.1    The
Residual Share shall be payable for any period that Crucell continues to have Crucell Collaboration Revenues. 

        9.6.2    The
Residual Share shall be determined as follows: 

	If Termination Occurs
 
	 	Residual Share

	Before Time for Section 5.1.2 Payment	 	•% of DSM Share
	

After Time for Section 5.1.2 Payment and provided that such payment has been made by DSM But Before Time for Section 5.1.3 Payment	
 	

•% of DSM Share
	

After Time for Section 5.1.3 Payment and provided that such payment has been made by DSM But Before Time for Section 5.1.4 Payment	
 	

•% of DSM Share
	

After Time for Section 5.1.4 Payment and provided that such payment has been made by DSM But Before Time for Section 5.1.5 Payment	
 	

•% of DSM Share
	

After Time for Section 5.1.5 Payment and provided that such payment has been made by DSM	
 	

•% of DSM Share

        9.6.3.    Any
such termination of this Agreement shall not be deemed to terminate the obligation of DSM to make payments to Crucell as provided by
Section 5.4, provided that the percentage of DSM Collaboration Revenues which is the subject of such payment following such termination shall be determined by subtracting (i) the
Residual Share determined in accordance with this Section from (ii) 100%. 

        9.7  In
addition, termination of this Agreement by DSM pursuant to this Section or by DSM pursuant to Section 9.2 or by Crucell pursuant to Section 9.5, shall
not be deemed to (i) terminate any license granted under and/or pursuant to this Agreement, provided that the DSM License shall, upon written notification by Crucell, automatically be converted
to a non-exclusive license upon such termination, (ii) waive any payment obligations which expressly provide that they survive the termination of this Agreement, or
(iii) terminate or waive any ancillary rights or obligations, such as rights of audit, integral and necessarily connected to such continuing licenses or payment obligations. 

16

 

        9.8  The
expiration of the Term or other termination of this Agreement shall not affect (i) obligations of either party accruing prior to the effectiveness of such
expiration or termination, or (ii) obligations which provide by their respective terms for survival and enforceability for a period beyond the Term, in each case which obligations shall
continue to be enforceable in accordance with their respective terms. 

        10.    Miscellaneous.    

        10.1.    This
Agreement shall be governed by and construed and enforced in accordance with the laws of The Netherlands without reference to its conflicts of laws
of principles. 

        10.2.    Notwithstanding
the foregoing, any disputes arising under or in connection with this Agreement which cannot be resolved amicably, shall be finally
submitted to arbitration in The Hague, Netherlands, in accordance with the rules of Conciliation and Arbitration of the International Chambre of Commerce, as amended from time to time. In any
arbitration pursuant to this Agreement, the award or decision shall be rendered by a majority of the members of an arbitration panel consisting of three members. 

        10.3.    Nonperformance
of any party (except for payment obligations) shall be excused to the extent that performance is rendered impossible by strike, fire,
earthquake, flood, governmental acts or orders or restrictions, failure of suppliers, or any other reason where failure to perform is beyond the reasonable control and not caused by the negligence or
intentional conduct or misconduct of the non-performing party. 

        10.4.    No
failure on the part of DSM or Crucell to exercise and no delay in exercising any right under this Agreement, or provided by statute or at law or in
equity or otherwise, shall impair, prejudice or constitute a waiver of any such right, nor shall any partial exercise of any such right preclude any other or further exercise thereof or the exercise
of any other right. 

        10.5.    Nothing
contained in this Agreement is intended implicitly, or is to be construed, to constitute DSM or Crucell as partners or agents of each other in
the legal sense. No party hereto shall have any express or implied right or authority to assume or create any obligations on behalf of or in the name of any other party or to bind any other party to
any contract, agreement or undertaking with any third party. 

        10.6.    All
notices, requests and other communications hereunder shall be in writing and shall be deemed to have been sufficiently given when received, whether
personally delivered or sent by registered or certified mail, return receipt requested, postage prepaid, or transmitted by facsimile 

17

 

with contemporaneous confirmation, in each case to the respective address specified below, or such other address as may be specified in writing to the other parties hereto: 

	To Crucell:	 	Crucell Holland B.V.

Archimedesweg 4,

2333 CN, Leiden

The Netherlands

Attn: Chief Business Officer

Facsimile No.: 31 71 524 8720
	

 	
 	

With a copy to:

Office of Chief Counsel

Facsimile No.: 31 71 524 8720
	

To DSM:	
 	

DSM Biologics

PO Box 43

6130 AA Sittard

Attn: Chief Executive Officer

Facsimile No.: 31 46 477 3179

With a copy to:

Legal Counsel

Facsimile No.: 31 46 477 3179

        10.7.    This
Agreement shall not be assignable by either party to any third party hereto without the written consent of the other party hereto, such consent not
unreasonably to be withheld; except DSM may assign this Agreement without Crucell's consent to any Affiliate or an entity that acquires substantially all of the business or assets of DSM, and Crucell
may assign this Agreement without DSM's consent to an Affiliate or an entity that acquires substantially all of the business or assets of Crucell, in each case whether by merger, sale of shares,
reorganization, acquisition or sale. The terms and conditions of this Agreement shall be binding on and inure to the benefit of the permitted successors and assigns of the parties. Either party
assigning this Agreement as per this Section shall promptly notify the other party in writing of any such assignment, prior to the assignment taking place. 

        10.8.    No
amendment or modification of any provision of this Agreement shall be effective unless in writing signed by the parties hereto. 

        10.9.    If
any provision hereof should be held invalid, illegal or unenforceable in any jurisdiction, all other provisions hereof shall remain in full force and
effect in such jurisdiction and shall be liberally construed in order to carry out the intentions of the parties hereto as nearly as may be possible. Such invalidity, illegality or unenforceability
shall not affect the validity, legality or enforceability of such provision in any other jurisdiction. 

        10.10.    Each
of the parties hereto agrees not to disclose to any third party, nor originate any public announcement, publicity or news release, whether to the
public or press, stockholders or otherwise, disclosing the existence, the terms of this Agreement performance under this Agreement or any amendment hereto without the prior written consent of each
other party hereto, such consent not be withheld unreasonably, except disclosures may be made to legal or financial advisors, accountants and investors on a need to know basis under circumstances that
reasonably ensure the confidentiality thereof, or to the extent required by law. If a party decides to make an announcement required by law, it shall give the other party five (5) business days
advance notice of the text of the announcement so that the other party shall have an opportunity to comment. If 

18

 

such other party does not comment within the five (5) business days, it will no longer have the opportunity to comment. 

        Notwithstanding
the foregoing, the parties shall agree upon a press release to announce the execution of this Agreement and the parties agree to schedule, coordinate and agree upon the
terms of a joint press conference with respect to this Agreement and the collaboration contemplated hereby; thereafter, Crucell and DSM may each disclose to third parties the information contained in
such press release and Q&A without the need for further approval by the other 

        10.11.    This
Agreement constitutes the entire agreement, both written and oral, with respect to the subject matter hereof, and supersedes all prior or
contemporaneous understandings or agreements,
whether written or oral, between DSM and Crucell with respect to such subject matter, which shall include, without being limited thereto, any and all term sheets and confidentiality agreements between
the parties with respect to such subject matter. 

        10.12.    This
Agreement may be executed in two or more counterparts, each of which shall be deemed an original, and all of which together, shall constitute one
and the same instrument. 

        10.13.    Headings
used herein are for convenience only and shall not in any way affect the construction of or be taken into consideration in interpreting this
Agreement. 

        10.14.    If
and to the extent mutually agreed upon by the parties, DSM and Crucell agree to mark and have their Affiliates, Licensees and customers mark all
Products they sell or distribute utilizing the technology covered by this Agreement in accordance with the applicable statute or regulations in the country or countries of manufacture and sale. 

        10.15.    If
any covenant, obligation or term hereunder or the application of any part of this Agreement to any party or circumstance shall, to any extent, be
invalid or unenforceable, as a matter of law, parties shall in good faith attempt to replace such covenant, obligation or term by a valid and enforceable covenant, obligation or term, which comes as
close in effect to the replaced covenant, obligation or term. Additionally, the remainder of this Agreement or the application of such covenants, agreements or obligations other than those which are
held to be invalid or unenforceable shall not be affected thereby and each covenant, obligation and agreement contained herein shall be separately valid and enforceable to the full extent permitted by
law, provided however, that in any such case the parties shall, if appropriate, adjust the relevant payment obligations accordingly. 

19

 

        IN
WITNESS WHEREOF, the parties hereto have caused this Agreement to be duly executed and delivered in duplicate originals as of the date first above written. 

	 	 	CRUCELL N.V.
	

 	
 	

By:	
 	

 
	 	 	 	 	

	

 	
 	
CRUCELL HOLLAND BV
	

 	
 	

By:	
 	

Crucell N.V., duly represented by
	

 	
 	

	

 	
 	
DSM BIOLOGICS HOLDING, INC.
	

 	
 	

By:	
 	

 
	 	 	 	 	

	

 	
 	

By:	
 	

 
	 	 	 	 	

	

 	
 	
DSM BIOLOGICS COMPANY, INC.
	

 	
 	

By:	
 	

 
	 	 	 	 	

	

 	
 	

By:	
 	

 
	 	 	 	 	

	

 	
 	
DSM BIOLOGICS COMPANY, B.V.
	

 	
 	

By:	
 	

 
	 	 	 	 	

	

 	
 	

By:	
 	

 
	 	 	 	 	

20

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Exhibit 4.4

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Exhibit 4.5    
  

 
  EMPLOYMENT CONTRACT    
  

THE UNDERSIGNED:  

	1.
	CRUCELL HOLLAND B.V., previously called IntroGene B.V., a private limited liability company having its registered office at
Archimedesweg 4, (2333 CN) Leiden, for the purposes hereof in accordance with the Articles of Association lawfully represented by Mr T. Logtenberg in his capacity as Managing Director of Crucell N.V.,
hereinafter to be referred to as "Crucell Holland";

	2
	CRUCELL N.V., a public limited liability company, having its registered office at Archimedesweg 4, (2333 CN) Leiden, for the purposes
hereof in accordance with the Articles of Association lawfully represented by Mr P.J. Strijkert, hereinafter to be referred to as "Crucell N.V.";

	3.
	Prof.
Dr. D. VALERIO, residing at (2342 AN) Oestgeest, Rhijngeesterstraatweg 11, hereinafter to be referred to as "Mr Valerio"; 

WHEREAS:  

	•
	Crucell
Holland, Crucell N.V. and Mr Valerio have entered into an employment contract on October 21, 2000 on terms in material aspects similar to the
terms of this employment contract;

	•
	Crucell
Holland, Crucell N.V. and Mr Valerio desire to incorporate the items agreed in the October 21, 2000 employment contract in manuscript and to
confirm the language of "Article 15: Indemnity" and "Articles 1.4, 1.5 Severance payment upon dismissal" in this employment contract;

	•
	"Crucell
Holland" acquired 100% of the shares of U-BiSys B.V. ("U-BiSys"), a private limited liability company. Crucell N.V. is the
holding company and is 100% shareholder of Crucell Holland; Moreover, Crucell N.V. is Managing Director of Crucell Holland and of U-Bisys.

	•
	Crucell
N.V. is listed on the Stock Exchange of Euronext Amsterdam N.V. and the NASDAQ;

	•
	Mr
Valerio is officially appointed, as from the date of the listing of Crucell N.V. on the Stock Exchange of Euronext Amsterdam N.V. and on the NASDAQ, as
Managing Director of Crucell N.V., by Shareholders resolution in accordance with the Articles of Association of Crucell N.V. As from the date of the listing of Crucell N.V. on the Stock Exchange of
Euronext Amsterdam N.V. and on the NASDAQ, Mr Valerio has been granted the title President and Chief Executive Officer Crucell N.V. by the Supervisory
Board of Crucell N.V.;

	•
	Mr
Valerio has been employed by Crucell Holland as Managing Director since July 1, 1993;

	•
	Mr
Valerio has resigned from his position as a Managing Director from Crucell Holland with effect from above referred date of
listing, which resignation is officially confirmed by a Shareholders' resolution in accordance with the Articles of Association of Crucell Holland. Mr
Valerio has, at his resignation as Managing Director, been fully and finally discharged from his responsibilities as Managing Director, in accordance with the required corporate proceedings.

	•
	Mr
Valerio will remain employed by Crucell Holland under the employment conditions described below. The underlying employment agreement will replace the
former employment agreement with Crucell Holland. The number of years of service of Mr Valerio ("the seniority") at Crucell Holland will be respected under the new employment agreement;

	•
	Mr
Valerio currently holds the position of Managing Director of a joint venture company of Crucell Holland and of a subsidiary of Crucell Holland; Mr Valerio
will continue to hold this position on request of Crucell N.V., in addition to the position of Chief Executive Officer of Crucell N.V.; 

1

 
	•
	Mr
Valerio holds since 1992 the position of University Professor in the field of Gene Therapy at the
University of Leiden. Valerio will continue to hold this position for one day a week on the same conditions, in addition to the position of Chief Executive
Officer of Crucell N.V.. The Chair under which Mr Valerio performs the activities has been installed since March 2000.

	•
	Mr
Valerio will perform his activities as University Professor at the University of Leiden through the foundation "Foundation
Leerstoel Leiden Crucell N.V. i.o.".

	•
	The
Shareholders' Body (as defined in the Articles of Association of Crucell N.V.) has appointed Mr Valerio as Managing Director in accordance with the
Articles of Association and authorised Mr P.J. Strijkert to sign the employment agreement on behalf of Crucell N.V..

	•
	The
parties wish to record the underlying employment agreement in writing. 

HAVE AGREED AS FOLLOWS:  

Article 1: Commencement, Term and Notice  

	1.
	The
employment contract will commence simultaneously with the date of listing of Crucell N.V. at the Stock Exchange of Euronext Amsterdam N.V. and NASDAQ, and is entered into for an
indefinite period of time.

	2.
	Mr
Valerio may terminate the employment contract with due observance of a notice period of 3 months, and Crucell Holland may terminate the employment contract with due
observance of a notice period of 6 months. Notice may be given only in writing.

	3.
	The
employment will end in any event without notice being required at the end of the month in which Mr Valerio reaches the age of 65.

	4.
	If
Crucell Holland dismisses Mr Valerio, parties will leave it to the decision of the competent court as to what the amount of severance pay shall be.

	5.
	Without
prejudice to the provisions referred to in this Article 1, the severance payment shall be a three (3) year gross salary, including holiday allowance, if the
dismissal of Mr Valerio is due to a Crucell change of control", either directly or indirectly. 

Article 2: Position  

	1.
	Mr
Valerio will hold the position of President and Chief Executive Officer for Crucell N.V..

	2.
	In
this position Mr Valerio will be entrusted with the management of Crucell N.V. and in this position Mr Valerio is appointed member of and President of the Board of Management of
Crucell N.V.. The duties Mr Valerio will be charged with, will be determined in consultation with the Board of Management, which duties can be amended in consultation with the Board of Management and
after approval of the Supervisory Board. Mr Valerio will act in his position of President and Chief Executive Officer in accordance with the obligations
and duties arising from this employment agreement and the Articles of Association of Crucell N.V.. Mr Valerio will perform his activities as a managing director of Crucell N.V. to his best abilities
and act as a diligent Managing Director. 

Article 3: Salary  

	1.
	The
Supervisory Board has officially determined in accordance with the Articles of Association of Crucell N.V. that Mr Valerio will be entitled to a gross basic annual salary of EUR
350,000.—including 8% holiday allowance. The salary shall be paid in twelve monthly equal instalments. The salary will include the remuneration of Mr Valerio's position as University
Professor at the University of Leiden. 

2

 
	2.
	Mr
Valerio will be eligible to an annual bonus to be determined by the Supervisory Board of Crucell N.V.. 

Article 4: Board of Management Optionscheme  

	1.
	Mr
Valerio will be granted at the listing of Crucell N.V. at the Stock Exchange of Euronext Amsterdam N.V. and NASDAQ, an initial number of stock options of 502.500 at 117% of the
introduction price of the Initial Public Offering ("IPO") under the applicable Crucell N.V. Optionscheme. A copy of the Crucell N.V. Optionscheme is attached to this employment contract as
Schedule 4.1.

	2.
	Subject
to the approval of the Remuneration Committee of Crucell N.V.'s Supervisory Board, Crucell Holland will provide Mr Valerio with a loan (in the amount of the applicable tax
assessment) for the payment of the tax assessment due and financing of exercising rights of options, resulting from the granting and exercising of the stock options. The terms and conditions of this
loan are determined in a Loan Agreement. With respect to the interest due on this loan, the Remuneration Committee may decide that Crucell Holland will increase the gross monthly salary of Mr Valerio
to effect that the net equivalent of this gross increase, can be used by Mr Valerio to pay the interest due. The loans granted to Mr Valerio will be re-payable in the events as stipulated
in the Loan Agreement, including but not limited to a lapse of a six month period after exercising an option agreement. Schedule 4.2 provides an overview of the current loans, with interest
rates and loan amount due. 

Article 5: Expense Allowance  

	1.
	Each
month, Mr Valerio will receive a minimum net fixed expense allowance in accordance with Crucell Holland's expense allowance policy.

	2.
	Expenses
that will not be deemed to be covered by the monthly expense allowance will qualify for compensation if they are related to the performance of Mr Valerio's position. A
statement of those expenses must be submitted to Crucell Holland prior to the end of the month following the month in which they were incurred. Expenses can be claimed upon submission of the original
receipt(s), specifying the business-related reason for which they were incurred. Crucell Holland will pay the expenses within one month after Mr Valerio has claimed them, provided that the statement
of expenses is sufficiently itemised, accompanied by the original receipt(s) and approved by Crucell Holland. 

Article 6: Telephone  

	1.
	Crucell
Holland will compensate Mr Valerio for the entire telephone bill of his private telephone and separate fax line (other than a mobile telephone), while deducting the wage tax
and employee insurance premiums due.

	2.
	Crucell
Holland will place at Mr Valerio's disposal a mobile telephone registered in Crucell Holland's name in accordance with Crucell Holland's mobile phone policy. 

Article 7: Car  

	1.
	Mr
Valerio is entitled to a lease car in the category 4 of Crucell Hollands's car policy. Mr Valerio will initially continue the use of his current lease car on the same
conditions. 

Article 8: Pension  

	1.
	Mr
Valerio will remain fully entitled to the pension provisions as has been agreed with Crucell Holland on December 1998 in "De Pensioenbrief". The rights and obligations with
respect to the 

3

 

pension
provisions are laid down in the "Pensioenbrief", a copy of which is attached to this employment contract as Schedule 8.1. However, Crucell Holland will, upon prior approval of Mr
Valerio, adjust the "Pensioenbrief" with respect to the actual Dutch tax legislation and the agreed pensionable salary of NLG 500,000, inclusive the yearly indexation, ultimately before
November 1, 2000, with full reservation of all rights and entitlements of Mr Valerio under the present Pensioenbrief. With respect to the adjusted pensionable salary, all years of service with
Crucell Holland as of July 1, 1993, will be taken into account with regard to the pensionaccrual under the Pensioenbrief. 

Article 9: Holidays  

	1.
	Mr
Valerio will be entitled to 30 days' holiday each calendar year, which may be taken in consultation with the Management Board of Crucell N.V.. 

Article 10: Illness and Incapacity for Work  

	1.
	If
Mr Valerio is unable to perform the agreed work due to illness, Mr Valerio will remain entitled to 100% of his last-earned gross salary for a period of 24 months
commencing on the first day of illness. Crucell Holland will take out and maintain a proper insurance in this respect.

	2.
	Crucell
Holland will furthermore maintain, at its own account, the Disability Insurance ("Arbeidsongeschiktheidsverzekering") for Mr Valerio, which provides for a monthly
allowance/pension in case of disablement, a percentage to be agreed upon of the last earned salary until the pensionable age. The last earned salary means the monthly gross basic salary. Crucell
Holland covenants in addition to the Disability Insurance to take out and maintain, at its own account, a proper "WAO-hiaat" insurance. 

Article 11: Health Insurance  

	1.
	After
having withheld the wage tax and social security premiums due, Crucell Holland will compensate Mr Valerio for 75% of his annual premium payable for a health insurance for Mr
Valerio and his family approved by Crucell Holland in advance. To that effect, Mr Valerio will provide a statement each year to be approved by Crucell Holland. Mr Valerio will provide Crucell Holland
with a copy of the policy. 

Article 12: Confidentiality  

	1.
	Neither
during the term of the employment contract nor upon termination thereof may Mr Valerio inform any third party in any form, directly or indirectly, of any particulars concerning
or related to the business conducted by Crucell Holland or its affiliated companies, which Mr Valerio could reasonably have known were not intended for third parties, regardless of whether such
information includes any reference to its confidential nature or ownership and regardless of how Mr Valerio learned of the particulars. 

Article 13: Sidelines  

	1.
	During
the term of the employment contract, Mr Valerio must refrain from undertaking or holding any sidelines or additional posts, such as committee work, or managerial or other
activities for associations, foundations or other organisations of an idealistic, cultural, sporting, political or other nature, whether or not for consideration, without Crucell Holland's prior
written consent, regardless of whether Crucell Holland is either partly or fully aware of such activities, if it is plausible that such activities may affect Mr Valerio's full dedication to his duties
within Crucell Holland's company, in terms of both time and attention. On request of Crucell Holland, Mr Valerio currently holds the position of Managing Director of a joint venture company of Crucell 

4

 

Holland
as well as of a subsidiary of Crucell Holland. As described in the preamble of this agreement, Mr Valerio holds and will continue to hold the position as professor at the University of Leiden
for one day a week. Furthermore Mr Valerio is a member of the "Curatorium Rijnlands Lyceum". 

Article 14: Intellectual Property Rights  

	1.
	All
intellectual property rights including but not limited to patent rights, design rights, copyrights and related rights, database rights, trademark rights and chip rights ensuing, in
the Netherlands and abroad, from the work performed by Mr Valerio under his employment contract and during a period of one year after termination thereof, will be exclusively vested in Crucell
Holland. For greater certainty intellectual property rights including but not limited to patent rights, design rights, copyrights and related rights, database rights, trademark rights and chip rights
ensuing, in the Netherlands and abroad, from the work performed by Mr Valerio in his position as University Professor in the field of Gene Therapy at the University of Leiden will not vest in Crucell
Holland.

	2.
	Insofar
as the rights specified herein are not vested in Crucell Holland by operation of law on the grounds of the employment contract between the parties, Mr Valerio covenants that he
will transfer
and, insofar as possible, hereby transfers to Crucell Holland any intellectual property rights of any nature in or arising from work performed by Mr Valerio in the discharge of his duties, both in the
Netherlands and abroad. 

Article 15: Indemnity  

	1.
	Crucell
N.V. will indemnify, in accordance with the Articles of Association of Crucell N.V., Mr Valerio against any and all liabilities and damage resulting from any and all possible
claims based upon and in connection with Mr Valerio's activities as a Managing Director of Crucell N.V., as a Managing Director of the joint venture company of Crucell Holland and as Managing Director
of subsidiary companies, or any other affiliated company in which Mr Valerio is a Managing Director. If Mr Valerio discovers that he may be held liable in connection with his position as Managing
Director of Crucell N.V., of the joint venture company, of subsidiary companies, or of any other affiliated companies, Mr Valerio will immediately report this to Crucell N.V.. Crucell N.V. must take
out and maintain a proper liability insurance with sufficient coverage in this regard. Crucell N.V. will see to a timely payment of the insurance premiums. 

Article 16: Applicable Law  

	1.
	This
employment contract and the appendices will be governed by the laws of the Netherlands. All disputes arising out of or in connection to this Agreement shall be referred to the
competent Dutch court.

	2.
	For
the avoidance of doubt, this employment contract cancels and supersedes all previous employment contracts, between Crucell Holland, Crucell N.V. and Mr Valerio, including but not
limited to the employment contract dated October 21, 2000. However the number of years of service of Mr Valerio since July 1, 1993 ("the seniority") at Crucell Holland will be respected
under this employment agreement. 

5

 

        Drawn
up in three original copies and signed in Leiden, on October 18, 2001. 

	For and on behalf of

Crucell Holland B.V.	 	The Employee
	

By	
 	

 	
 	

By	
 	

 
	 	 	
 Crucell N.V.	 	 	 	
 Prof. Dr. Domenico Valerio
	

Prof. Dr. T. Logtenberg
 Managing Director

(Statutair directeur)	
 	

 	
 	

 
	

For and on behalf of

Crucell N.V.	
 	

 	
 	

 
	

By	
 	

 	
 	

 	
 	

 
	 	 	
 Dr. P.J. Strijkert
 Chairman of the Supervisory Board	 	 	 	 

6

QuickLinks

Exhibit 4.5

EMPLOYMENT CONTRACT

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