Document:

<PAGE>
                                                                    Exhibit 10.4

                          ALNYLAM PHARMACEUTICALS, INC.

                        2004 EMPLOYEE STOCK PURCHASE PLAN

      The purpose of this Plan is to provide eligible employees of Alnylam
Pharmaceuticals, Inc., a Delaware corporation (the "Company"), and certain of
its subsidiaries with opportunities to purchase shares of the Company's common
stock, $.0001 par value (the "Common Stock"). An aggregate of 315,789 shares of
Common Stock have been approved for this purpose. This Plan is intended to
qualify as an "employee stock purchase plan" as defined in Section 423 of the
Internal Revenue Code of 1986, as amended (the "Code"), and the regulations
promulgated thereunder, and shall be interpreted consistent therewith.

      1. Administration. The Plan will be administered by the Company's Board of
Directors (the "Board") or by a Committee appointed by the Board (the
"Committee"). The Board or the Committee has authority to make rules and
regulations for the administration of the Plan and its interpretation and
decisions with regard thereto shall be final and conclusive.

      2. Eligibility. All employees of the Company and all employees of any
subsidiary of the Company (as defined in Section 424(f) of the Code) designated
by the Board or the Committee from time to time (a "Designated Subsidiary"), are
eligible to participate in any one or more of the offerings of Options (as
defined in Section 9) to purchase Common Stock under the Plan provided that:

                  (a) they are customarily employed by the Company or a
      Designated Subsidiary for more than twenty (20) hours a week and for more
      than five (5) months in a calendar year; and

                  (b)   they have been employed by the Company or a
      Designated Subsidiary for at least six (6) months prior to enrolling in
      the Plan;

                  (c)   they are employees of the Company or a Designated
      Subsidiary on the first day of the applicable Plan Period (as defined
      below); and

                  (d) in the case of an executive officer of the Company or a
      Designated Subsidiary, they are not considered a "highly compensated
      individual" within the meaning of Section 414(q) of the Code.

      No employee may be granted an option hereunder if such employee,
immediately after the option is granted, owns 5% or more of the total combined
voting power or value of the stock of the Company or any subsidiary. For
purposes of the preceding sentence, the attribution rules of Section 424(d) of
the Code shall apply in determining the stock ownership of an employee, and all
stock which the employee has a contractual right to purchase shall be treated as
stock owned by the employee.

      3. Offerings. The Company will make one or more offerings ("Offerings") to
employees to purchase stock under this Plan. Offerings will begin each November
1 or the first

<PAGE>
business day thereafter (the "Offering Commencement Dates"). Each Offering
Commencement Date will begin a twelve-month period (a "Plan Period") during
which payroll deductions will be made and held for the purchase of Common Stock
at the end of the Plan Period. The Board or the Committee may, at its
discretion, choose a different Plan Period of twelve (12) months or less for
subsequent Offerings. Notwithstanding anything to the contrary, the first Plan
Period shall begin on the later of November 1, 2004 or the first date that the
Common Stock is publicly traded following the Company's IPO (the "IPO Date"),
and shall end on October 31, 2005.

      4. Participation. An employee eligible on the Offering Commencement Date
of any Offering may participate in such Offering by completing and forwarding a
payroll deduction authorization form to the employee's appropriate payroll
office at least five (5) business days prior to the applicable Offering
Commencement Date. The form will authorize a regular payroll deduction from the
Compensation received by the employee during the Plan Period. Unless an employee
files a new form or withdraws from the Plan, his deductions and purchases will
continue at the same rate for future Offerings under the Plan as long as the
Plan remains in effect. The term "Compensation" means the amount of money
reportable on the employee's Federal Income Tax Withholding Statement, excluding
overtime, shift premium, incentive or bonus awards, allowances and
reimbursements for expenses such as relocation allowances for travel expenses,
income or gains on the exercise of Company stock options or stock appreciation
rights, amounts imputed in respect of benefit programs and similar items,
whether or not shown on the employee's Federal Income Tax Withholding Statement,
but including, in the case of salespersons, sales commissions to the extent
determined by the Board or the Committee.

      5. Deductions. The Company will maintain payroll deduction accounts for
all participating employees. With respect to any Offering made under this Plan,
an employee may authorize a payroll deduction in any dollar amount up to a
maximum of 15% of the Compensation he or she receives during the Plan Period or
such shorter period during which deductions from payroll are made. Payroll
deductions may be at the rate of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%,
12%, 13%, 14% or 15% of Compensation with any change in compensation during the
Plan Period to result in an automatic corresponding change in the dollar amount
withheld. The minimum payroll deduction is such percentage of compensation as
may be established from time to time by the Board or the Committee.

      6. Deduction Changes. An employee may decrease or discontinue his payroll
deduction once during any Plan Period, by filing a new payroll deduction
authorization form. However, an employee may not increase his payroll deduction
during a Plan Period. If an employee elects to discontinue his payroll
deductions during a Plan Period, but does not elect to withdraw his funds
pursuant to Section 8 hereof, funds deducted prior to his election to
discontinue will be applied to the purchase of Common Stock on the Exercise Date
(as defined below).

      7. Interest. Interest will not be paid on any employee accounts.

      8. Withdrawal of Funds. An employee may at any time prior to the close of
business on the last business day in a Plan Period and for any reason
permanently draw out the balance accumulated in the employee's account and
thereby withdraw from participation in an Offering. Partial withdrawals are not
permitted. The employee may not begin participation again during

                                     - 2 -
<PAGE>
the remainder of the Plan Period. The employee may participate in any subsequent
Offering in accordance with terms and conditions established by the Board or the
Committee.

      9. Purchase of Shares. On the Offering Commencement Date of each Plan
Period, the Company will grant to each eligible employee who is then a
participant in the Plan an option ("Option") to purchase on the last business
day of such Plan Period (the "Exercise Date"), at the Option Price hereinafter
provided for, the largest number of whole shares of Common Stock of the Company
as does not exceed the number of shares determined by multiplying $2,083 by the
number of full months in the Offering Period and dividing the result by the
closing price (as defined below) on the Offering Commencement Date of such Plan
Period.

      Notwithstanding the above, no employee may be granted an Option (as
defined in Section 9) which permits his rights to purchase Common Stock under
this Plan and any other employee stock purchase plan (as defined in Section
423(b) of the Code) of the Company and its subsidiaries, to accrue at a rate
which exceeds $25,000 of the fair market value of such Common Stock (determined
at the Offering Commencement Date of the Plan Period) for each calendar year in
which the Option is outstanding at any time.

      The purchase price for each share purchased will be 85% of the closing
price of the Common Stock on (i) the first business day of such Plan Period or
(ii) the Exercise Date, whichever closing price shall be less. Such closing
price shall be (a) the closing price on any national securities exchange on
which the Common Stock is listed, (b) the closing price of the Common Stock on
the Nasdaq National Market or (c) the average of the closing bid and asked
prices in the over-the-counter-market, whichever is applicable, as published in
The Wall Street Journal; provided that, with respect to the first Plan Period,
if the first day of such Plan Period is the IPO Date, the closing price of the
Common Stock on the first business day of such Plan Period shall be deemed to be
the initial public offering price for the Common Stock, as set forth in the
final prospectus relating to the IPO. If no sales of Common Stock were made on
such a day, the price of the Common Stock for purposes of clauses (a) and (b)
above shall be the reported price for the next preceding day on which sales were
made.

      Each employee who continues to be a participant in the Plan on the
Exercise Date shall be deemed to have exercised his Option at the Option Price
on such date and shall be deemed to have purchased from the Company the number
of full shares of Common Stock reserved for the purpose of the Plan that his
accumulated payroll deductions on such date will pay for, but not in excess of
the maximum number determined in the manner set forth above.

      Any balance remaining in an employee's payroll deduction account at the
end of a Plan Period will be automatically refunded to the employee, except that
any balance which is less than the purchase price of one share of Common Stock
will be carried forward into the employee's payroll deduction account for the
following Offering, unless the employee elects not to participate in the
following Offering under the Plan, in which case the balance in the employee's
account shall be refunded.

      10. Issuance of Certificates. Certificates representing shares of Common
Stock purchased under the Plan may be issued only in the name of the employee,
in the name of the employee and another person of legal age as joint tenants
with rights of survivorship, or (in the

                                     - 3 -
<PAGE>
Company's sole discretion) in the name of a brokerage firm, bank or other
nominee holder designated by the employee. The Company may, in its sole
discretion and in compliance with applicable laws, authorize the use of book
entry registration of shares in lieu of issuing stock certificates.

      11. Rights on Retirement, Death or Termination of Employment. In the event
of a participating employee's termination of employment prior to the last
business day of a Plan Period, no payroll deduction shall be taken from any pay
due and owing to an employee and the balance in the employee's account shall be
paid to the employee or, in the event of the employee's death, (a) to a
beneficiary previously designated in a revocable notice signed by the employee
(with any spousal consent required under state law) or (b) in the absence of
such a designated beneficiary, to the executor or administrator of the
employee's estate or (c) if no such executor or administrator has been appointed
to the knowledge of the Company, to such other person(s) as the Company may, in
its discretion, designate. If, prior to the last business day of the Plan
Period, the Designated Subsidiary by which an employee is employed shall cease
to be a subsidiary of the Company, or if the employee is transferred to a
subsidiary of the Company that is not a Designated Subsidiary, the employee
shall be deemed to have terminated employment for the purposes of this Plan.

      12. Optionees Not Stockholders. Neither the granting of an Option to an
employee nor the deductions from his pay shall constitute such employee a
stockholder of the shares of Common Stock covered by an Option under this Plan
until such shares have been purchased by and issued to him.

      13. Rights Not Transferable. Rights under this Plan are not transferable
by a participating employee other than by will or the laws of descent and
distribution, and are exercisable during the employee's lifetime only by the
employee.

      14. Application of Funds. All funds received or held by the Company under
this Plan may be combined with other corporate funds and may be used for any
corporate purpose.

      15. Adjustment in Case of Changes Affecting Common Stock. In the event of
a subdivision of outstanding shares of Common Stock, or the payment of a
dividend in Common Stock, the number of shares approved for this Plan, and the
share limitation set forth in Section 9, shall be increased proportionately, and
such other adjustment shall be made as may be deemed equitable by the Board or
the Committee. In the event of any other change affecting the Common Stock, such
adjustment shall be made as may be deemed equitable by the Board or the
Committee to give proper effect to such event.

      16. Merger. If the Company shall at any time merge or consolidate with
another corporation and the holders of the capital stock of the Company
immediately prior to such merger or consolidation continue to hold at least a
majority by voting power of the capital stock of the surviving corporation
("Continuity of Control"), the holder of each Option then outstanding will
thereafter be entitled to receive at the next Exercise Date upon the exercise of
such Option for each share as to which such Option shall be exercised the
securities or property which a holder of one share of the Common Stock was
entitled to upon and at the time of such merger or consolidation, and the Board
or the Committee shall take such steps in connection with

                                     - 4 -
<PAGE>
such merger or consolidation as the Board or the Committee shall deem necessary
to assure that the provisions of Section 15 shall thereafter be applicable, as
nearly as reasonably may be, in relation to the said securities or property as
to which such holder of such Option might thereafter be entitled to receive
thereunder.

      In the event of a merger or consolidation of the Company with or into
another corporation which does not involve Continuity of Control, or of a sale
of all or substantially all of the assets of the Company while unexercised
Options remain outstanding under the Plan, (a) subject to the provisions of
clauses (b) and (c), after the effective date of such transaction, each holder
of an outstanding Option shall be entitled, upon exercise of such Option, to
receive in lieu of shares of Common Stock, shares of such stock or other
securities as the holders of shares of Common Stock received pursuant to the
terms of such transaction; or (b) all outstanding Options may be cancelled by
the Board or the Committee as of a date prior to the effective date of any such
transaction and all payroll deductions shall be paid out to the participating
employees; or (c) all outstanding Options may be cancelled by the Board or the
Committee as of the effective date of any such transaction, provided that notice
of such cancellation shall be given to each holder of an Option, and each holder
of an Option shall have the right to exercise such Option in full based on
payroll deductions then credited to his account as of a date determined by the
Board or the Committee, which date shall not be less than ten (10) days
preceding the effective date of such transaction.

      17. Amendment of the Plan. The Board may at any time, and from time to
time, amend this Plan in any respect, except that (a) if the approval of any
such amendment by the shareholders of the Company is required by Section 423 of
the Code, such amendment shall not be effected without such approval, and (b) in
no event may any amendment be made which would cause the Plan to fail to comply
with Section 423 of the Code.

      18. Insufficient Shares. In the event that the total number of shares of
Common Stock specified in elections to be purchased under any Offering plus the
number of shares purchased under previous Offerings under this Plan exceeds the
maximum number of shares issuable under this Plan, the Board or the Committee
will allot the shares then available on a pro rata basis.

      19. Termination of the Plan. This Plan may be terminated at any time by
the Board. Upon termination of this Plan all amounts in the accounts of
participating employees shall be promptly refunded.

      20. Governmental Regulations. The Company's obligation to sell and deliver
Common Stock under this Plan is subject to listing on a national stock exchange
or quotation on the Nasdaq National Market (to the extent the Common Stock is
then so listed or quoted) and the approval of all governmental authorities
required in connection with the authorization, issuance or sale of such stock.

      21. Governing Law. The Plan shall be governed by Delaware law except to
the extent that such law is preempted by federal law.

                                     - 5 -
<PAGE>
      22. Issuance of Shares. Shares may be issued upon exercise of an Option
from authorized but unissued Common Stock, from shares held in the treasury of
the Company, or from any other proper source.

      23. Notification upon Sale of Shares. Each employee agrees, by entering
the Plan, to promptly give the Company notice of any disposition of shares
purchased under the Plan where such disposition occurs within two (2) years
after the date of grant of the Option pursuant to which such shares were
purchased.

      24. Special Provisions for First Plan Period. If the first day of the
first Plan Period is the IPO Date, the following provisions of this Section 24
shall apply with respect to the first Plan Period notwithstanding any provision
of the Plan to the contrary:

            (a) Every eligible employee shall automatically become a participant
in the Plan for the first Plan Period at the highest percentage of Compensation
permitted under Section 5. No payroll deductions shall be required for the first
Plan Period; however, a participant may, at any time after the effectiveness of
the Plan's Registration Statement on Form S-8, elect to have payroll deductions
up to the aggregate amount which would have been credited to his or her account
if a deduction of fifteen percent (15%) of the Compensation which he or she
received on each pay day during the first Plan Period had been made (the
"Maximum Amount") or decline to participate by filing an appropriate
subscription agreement.

            (b) Upon the automatic exercise of a participant's option on the
Exercise Date for the first Plan Period, a participant shall be permitted to
purchase shares with (i) the accumulated payroll deductions in his or her
account, if any, (ii) a direct payment from the participant, or (iii) a
combination thereof; provided, however that the total amount applied to the
purchase may not exceed the Maximum Amount.

      25. Withholding. Each employee shall, no later than the date of the event
creating the tax liability, make provision satisfactory to the Board for payment
of any taxes required by law to be withheld in connection with any transaction
related to Options granted to or shares acquired by such employee pursuant to
the Plan. The Company may, to the extent permitted by law, deduct any such taxes
from any payment of any kind otherwise due to an employee.

      26. Effective Date and Approval of Shareholders. The Plan shall take
effect on the IPO Date, subject to approval by the shareholders of the Company
as required by Section 423 of the Code, which approval must occur within twelve
months of the adoption of the Plan by the Board.

                                     - 6 -<PAGE>

                                                                  EXECUTION COPY

                                                                    EXHIBIT 10.1

          CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE
         SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE OMISSIONS.

                              AMENDED AND RESTATED
                                LICENSE AGREEMENT

                                     BETWEEN

                          TRANSKARYOTIC THERAPIES, INC.

                                       AND

                          AVENTIS PHARMACEUTICALS INC.

                           DATED AS OF MARCH 26, 2004

<PAGE>

                      AMENDED AND RESTATE LICENSE AGREEMENT

      THIS AMENDED AND RESTATED LICENSE AGREEMENT dated as of March 26, 2004
(the "Agreement") is made between TRANSKARYOTIC THERAPIES, INC., a Delaware
corporation having its principal place of business at 700 Main Street,
Cambridge, Massachusetts 02139 ("TKT") and AVENTIS PHARMACEUTICALS INC., a
Delaware corporation (formerly known as Hoechst Marion Roussel, Inc. and
previously formerly known as Marion Merrell Dow Inc.) ("Aventis").

                                    RECITALS

      WHEREAS, TKT has filed patent applications necessary to exploit
discoveries relating to the expression of gene-activated erythropoietin protein
in eukaryotic cells and possesses certain related know-how and expertise.

      WHEREAS, Aventis desires to license TKT's patent rights and certain
related know-how and expertise relating to gene-activated erythropoietin protein
in the Aventis Territory (as defined below) and obtain TKT's assistance for
development of such discoveries.

      WHEREAS, TKT and Aventis previously entered into that certain License
Agreement dated as of May 18, 1994, as amended and restated as of March 1, 1995
(the "Original License Agreement") regarding gene-activated erythropoietin
protein and now desire to amend and restate the Original License Agreement in
its entirety as follows.

      NOW THEREFORE, in consideration of the premises and of the covenants
herein contained, the sufficiency of which is hereby acknowledged, and intending
to be legally bound, the parties hereto mutually agree as follows:

                                    ARTICLE 1

                                   DEFINITIONS

      For purposes of this Agreement, the terms defined in this Article shall
have the meanings specified below:

      1.1   "Affiliate" shall mean any corporation or other entity which
controls, is controlled by, or is under common control with a party to this
Agreement. A corporation or other entity shall be regarded as in control of
another corporation or entity if it owns or directly or indirectly controls more
than fifty percent (50%) of the voting stock or other ownership interest of the
other corporation or entity, or if it possesses, directly or indirectly, the
power to direct or cause the direction of the management and policies of the
corporation or other entity or the power to elect or appoint fifty percent (50%)
or more of the members of the governing body of the corporation or other entity.
Notwithstanding the foregoing, the Dow Chemical Company shall not be considered
an Affiliate of Aventis for purposes of this Agreement.

                                      -2-
<PAGE>

      1.2   "Amendment Effective Date" shall mean the date first set forth
above.

      1.3   "Aventis Technology" shall mean all inventions, trade secrets,
trademarks, copyrights, know-how, data, regulatory submissions and other
intellectual property of any kind (including any proprietary biological
materials, compounds or reagents) which are owned or controlled by, or licensed
(with the right to sublicense) to, Aventis as of the Amendment Effective Date,
relating to or necessary or useful for the manufacture, use, distribution or
sale of GA-EPO, including but not limited to any patents or patent applications
licensed from Third Parties; provided, however, that [**] shall not be
considered Aventis Technology. With respect to Aventis Technology which has been
licensed to Aventis by a Third Party, [**].

      1.4   "Aventis Territory" shall mean the United States of America (and its
territories and possessions, including without limitation, Puerto Rico).

      1.5   "BLA" shall mean a biologics license application filed with the FDA
after completion of human clinical trials to obtain marketing approval for
GA-EPO covered by the TKT Patent Rights or which uses the TKT Technology in the
United States or any comparable application filed with the regulatory
authorities of a country other than the United States to obtain marketing
approval for GA-EPO covered by the TKT Patent Rights or which uses the TKT
Technology in that country.

      1.6   "Commercially Reasonable Efforts" shall mean, with respect to
GA-EPO, those efforts and resources which would be used by Aventis consistent
with its normal business practices for a product of similar market potential, at
a similar stage of its product life, taking into account the establishment of
the product in the marketplace, the competitiveness of the marketplace, the
proprietary position of the product, the regulatory status involved, the
profitability of the product, as well as other relevant factors.

      1.7   "Development Committee" shall mean the joint committee composed of
representatives of TKT and Aventis described in Section 6.2 of this Agreement.

      1.8   "Development Phase" shall mean the second phase of the Program,
which shall commence upon delivery by TKT to Aventis, after acceptance by the
R&D Oversight Committee, of the cell line produced by TKT, and shall consist of
the preclinical and clinical development of GA-EPO covered by the TKT Patent
Rights or which uses the TKT Technology and the preparation and filing of
supporting regulatory submissions until, with respect to each country in the
Aventis Territory, final marketing approval for GA-EPO covered by the TKT Patent
Rights or which uses the TKT Technology is obtained in such country.

      1.9   "Effective Date" shall mean May 18, 1994.

      1.10  "First Commercial Sale" of GA-EPO covered by the TKT Patent Rights
or which uses the TKT Technology shall mean the first sale for use or
consumption by the general public of GA-EPO covered by the TKT Patent Rights or
which uses the TKT Technology in a country in the Aventis Territory or TKT
Territory, as applicable, after

                                      -3-
<PAGE>

required marketing and pricing approval has been granted by the governing health
authority of such country.

      1.11  "FDA" shall mean the United States Food and Drug Administration.

      1.12  "Fully Absorbed Costs" shall mean the direct variable and direct
fixed costs associated with the conduct of the Research Phase or the Development
Phase. Direct variable costs shall be deemed to be the cost of labor, raw
materials, supplies and other resources directly consumed in the conduct of the
Research Phase or the Development Phase. Direct fixed costs shall be deemed to
be the cost of utilities, insurance, equipment depreciation and other fixed
costs directly related to the conduct of the Research Phase or the Development
Phase. Fixed costs shall be allocated based upon the proportion of such costs
directly attributable to support of the Research Phase or the Development Phase.
All costs determinations made hereunder shall be made in accordance with
generally accepted accounting principles consistently applied.

      1.13  "GA-EPO" shall mean all pharmaceutical and other formulations of
gene-activated erythropoietin protein, including all injectable and orally
available formulations, line extensions, combination products, delivery systems,
and dosage forms related thereto, but excluding any gene therapy processes or
products.

      1.14  "IND" shall mean an investigational new drug application filed with
the FDA prior to beginning clinical trials in humans or any comparable
application filed with the regulatory authorities of a country other than the
United States prior to beginning clinical trials in humans in that country, with
respect to GA-EPO covered by the TKT Patent Rights or which uses the TKT
Technology.

      1.15  "Manufacturing Know-How" shall mean all inventions, discoveries,
improvements and other technology, whether or not patentable or copyrightable,
and any patent applications, patents or copyrights based thereon, relating to or
necessary or useful for the production and packaging of GA-EPO covered by the
TKT Patent Rights or which uses the TKT Technology or Aventis Technology.

      1.16  "[**]" means any modification, enhancement or improvement made to
the [**].

      1.17  "[**]" shall mean all inventions, trade secrets, know-how, data and
other intellectual property of any kind which is owned, controlled by or
licensed to [**] owned by Aventis.

      1.18  "Net Sales" with respect to (i) sales of GA-EPO covered by the TKT
Patent Rights or which uses the TKT Technology, and (ii) sales of [**] (as
defined below) in the case of TKT only, shall mean the invoiced amount billed
for GA-EPO finished product in final packing form to the first Third Party trade
purchaser (a "Trade Customer") by Aventis or TKT, as applicable (each, a
"Selling Party"), or the Affiliates of, or distributors which are

                                      -4-
<PAGE>

not Affiliates of, a Selling Party, or by licensees of a Selling Party or, to
the extent permitted in subsections 3.1.2 or 3.2.2, by permitted sublicensees of
Aventis or TKT, as the case may be, (it being understood that wholesalers which
are not Affiliates of a Selling Party shall be considered Trade Customers),
less, whether or not such costs are invoiced separately to such Trade Customer,
(a) amounts refunded or credited for GA-EPO which was rejected, spoiled,
damaged, out-dated or returned, (b) freight, shipment and insurance costs
incurred in transporting GA-EPO to such customers, (c) quantity, trade, case,
and other discounts, rebates (including, without limitation, pursuant to
governmental regulation), chargebacks, retroactive price reductions, credits or
allowances allowed or taken (subject to post-period adjustment if allowed but
not taken within three months of the end of the calendar year in which such
credit or allowance is allowed), and (d) taxes, tariffs, customs duties and
surcharges and other governmental charges incurred in connection with the sale,
exportation or importation of GA-EPO. The transfer of GA-EPO by the Selling
Party or one of its Affiliates to another Affiliate of the Selling Party shall
not be considered a sale; in such cases, Net Sales shall be determined based on
the invoiced sales price by the Affiliate to the Trade Customer, less the
deductions allowed under this Section. The Selling Party shall be deemed to have
sold a "Bundled Product" if GA-EPO finished product is sold by the Selling Party
pursuant to an agreement with a Trade Customer specifying, for a combination of
products or services, (i) a single price, (ii) other terms of purchase not
separately identifying either a price per product or the effective deductions
referred to above per product or (iii) a price for units of GA-EPO which is
discounted below the Selling Party's standard invoice price per unit of GA-EPO
by at least five percentage points more than the amount that any other product
or service in the Bundled Product is discounted below such other product's or
service's standard invoice price. In order to calculate the Net Sales of GA-EPO
included in a Bundled Product (a) in the case of the foregoing clauses (i) and
(ii), the total net Sales of the Bundled Product shall be multiplied by a
fraction the numerator of which shall be the product of the number of units of
GA-EPO sold multiplied by the standard invoice price per unit of GA-EPO, and the
denominator of which shall be the sum, or all products or services included in
the Bundled Product, of the product of the number of units sold for each product
or service in the Bundled Product multiplied by the standard invoice price per
unit for each such product or service and (b) in the case of the foregoing
clause (iii), the parties will determine whether an adjustment to Net Sales is
appropriate and, if so, a mutually agreeable method of calculation. If GA-EPO is
formulated by the Selling Party with one or more different active biological or
chemical ingredients and such formulation is sold in finished product form, then
the Selling Party shall be deemed to have sold a "Combination Product." In order
to calculate the Net Sales of GA-EPO included in a Combination Product, the
total invoice price for the Combination Product shall be multiplied by a
fraction, the numerator of which shall be the product of the dosage of GA-EPO
included in the Combination Product multiplied by the standard invoice price of
such dosage of GA-EPO, and the denominator of which shall be the sum, for all
individual active ingredients included in the Combination Product, of the
product of the dosage of each product included in the Combination Product
multiplied by the standard invoice price of such dosage of each such product. If
it is not possible to determine the standard invoice price for an active
ingredient of the Combination Product, then the standard invoice price for such
individual active ingredient shall be the fully allocated cost of manufacture
therefor determined in accordance with standard cost accounting principles, as
adjusted to reflect the Selling Party's standard profit margin for like

                                      -5-
<PAGE>

products. The amount of Net Sales for any period shall be determined on the
basis of sales recorded in the ordinary course on the books and records of the
Selling Party (or any Affiliate of the Selling Party) during such period in
accordance with Generally Accepted Accounting Principles and with past practice,
without reference to the effects of any subsequent audit adjustments which
result in any of such sales being recognized by the Selling Party in another
period. Net Sales shall not include any sales of GA-EPO by by TKT, its
Affiliates or sublicensees in Japan.

      1.19  "Program" shall mean the collaboration by TKT and Aventis described
in this Agreement.

      1.20  "R&D Oversight Committee" shall mean the joint committee composed of
representatives of TKT and Aventis described in Section 6.1 of this Agreement.

      1.21  "Research Phase" shall mean the first stage of the Program
commencing on the Effective Date, during which a cell line for the expression of
GA-EPO covered by the TKT Patent Rights or which uses the TKT Technology will be
prepared by TKT and delivered to Aventis. The Research Phase is more fully
described in Article 4.

      1.22  "Research Program" shall mean the GA-EPO research program described
in Section 4.1 of this Agreement.

      1.23  "Third Party" shall mean any entity other than TKT or Aventis and
their respective Affiliates.

      1.24  "TKT Patent Rights" shall mean all present and, at Aventis's
election, future patents, patent applications, patent extensions, certificates
of invention, or applications for certificates of invention, together with any
divisions, continuations or continuations-in-part thereof, which are owned or
controlled by TKT relating to or necessary or useful for the manufacture, use,
distribution or sale of GA-EPO, including without limitation those specified on
Schedule 1.23 hereto.

      1.25  "TKT Technology" shall mean all present and future inventions, trade
secrets, copyrights, know-how, data, regulatory submissions and other
intellectual property of any kind (including any proprietary biological
materials, compounds or reagents but not including TKT Patent Rights) which are
owned or controlled by, or licensed (with the right to sublicense) to, TKT
relating to or necessary or useful for the manufacture, use, distribution or
sale of GA-EPO, including but not limited to any patents or patent applications
licensed from Third Parties. With respect to TKT Technology which has been
licensed to TKT by a Third Party, (i) Aventis agrees to assume and pay for its
portion of any costs, expenses, fees or royalties associated with its use of
sublicense rights relating to such licensed TKT Technology to the extent
described in Section 8.7, and (ii) if TKT does not currently have the right to
sublicense such intellectual property to Aventis hereunder, such license is
listed on Schedule 1.24 hereto and TKT shall use commercially reasonable efforts
to obtain the right to sublicense such intellectual property (as well as any
intellectual property licensed to TKT hereafter which is included in the TKT
Technology), to Aventis hereunder.

                                      -6-
<PAGE>

      1.26  "TKT Territory" shall mean all of the countries of the world,
excluding those countries comprising the Aventis Territory.

                                    ARTICLE 2

                               SCOPE AND STRUCTURE

      2.1   General. TKT and Aventis wish to establish an agreement with respect
to GA-EPO. During the course of the Program, TKT and Aventis shall communicate
regularly and shall assume different rights and responsibilities, all as more
specifically described herein.

                                    ARTICLE 3

               LICENSE GRANTS; MANUFACTURING AND MARKETING RIGHTS

      3.1   Grant of License Rights by TKT to Aventis.

            3.1.1 Exclusive GA-EPO License. TKT hereby grants to Aventis an
exclusive, perpetual, right and license under the TKT Patent Rights and the TKT
Technology to (i) research, develop, import, make and have made GA-EPO
throughout the world for distribution and sale in the Aventis Territory and (ii)
market, have marketed, offer for sale, sell, have sold, distribute, have
distributed and otherwise commercialize GA-EPO in the Aventis Territory.

            3.1.2 Sublicenses of GA-EPO. Aventis shall have the right to grant
sublicenses under the TKT Patent Rights and the TKT Technology license granted
by TKT to Aventis under subsection 3.1.1 to Affiliates of Aventis and, with the
written consent of TKT, which shall not be unreasonably withheld, to entities
which are not Affiliates of Aventis. In connection with such sublicense, Aventis
may provide that the sublicensee shall pay directly to TKT any amounts which may
become due in accordance with Section 7.2, provided, however, that Aventis shall
in any event remain liable for the payment of all such amounts notwithstanding
any such provision between Aventis and its sublicensee. Upon TKT's request, and
to the extent that Aventis is not contractually prohibited from doing so,
Aventis will provide a copy of such sublicenses to TKT.

            3.1.3 Exclusive Manufacturing Know-How License. TKT hereby grants to
Aventis a worldwide, perpetual, and exclusive and, except as provided below,
fully paid-up and royalty-free right and license under Manufacturing Know-How
owned or controlled by, or licensed (subject to the provisions of this
subsection 3.1.3, with the right to sublicense) to, TKT prior to the Amendment
Effective Date to make and have made GA-EPO throughout the world for
distribution and sale in the Aventis Territory. With respect to Manufacturing
Know-How which has been licensed to TKT by a Third Party, (i) Aventis [**] with
its sublicense of such Manufacturing Know-How, and (ii) if TKT does not
currently have the right to sublicense such intellectual property to Aventis
hereunder, such license is listed on Schedule 3.1.3 hereto and TKT shall use

                                      -7-
<PAGE>

commercially reasonable efforts to obtain the right to sublicense such
intellectual property to Aventis hereunder for such limited purposes.

            3.1.4 Sublicenses of Manufacturing Know-How. Aventis shall have the
right to grant sublicenses under the Manufacturing Know-How license granted by
TKT to Aventis under subsection 3.1.3 to Affiliates of Aventis and, with the
written consent of TKT, which shall not be unreasonably withheld, to entities
which are not Affiliates of Aventis. Aventis will provide a copy of such
sublicenses to TKT.

      3.2   Grant of License Rights by Aventis to TKT.

            3.2.1 Exclusive GA-EPO License. Aventis hereby grants to TKT an
exclusive, perpetual, right and license under the Aventis Technology to (i)
research, develop, import, make and have made GA-EPO throughout the world
(subject to Section 3.2.5) for distribution and sale in the TKT Territory and
(ii) market, have marketed, offer for sale, sell, have sold, distribute, have
distributed and otherwise commercialize GA-EPO in the TKT Territory.

            3.2.2 Sublicenses of GA-EPO. TKT shall have the right to grant
sublicenses under the Aventis Technology license granted by Aventis to TKT under
subsection 3.2.1. In connection with such sublicense, TKT may provide that the
sublicensee shall pay directly to Aventis any amounts which may become due in
accordance with Section 7.2; provided, however, that TKT shall in any event
remain liable for the payment of all such amounts notwithstanding any such
provision between TKT and its sublicensee. TKT shall have no right to license or
sublicense any right to market, have marketed, offer for sale, sell, have sold,
distribute, have distributed or otherwise commercialize GA-EPO in Canada without
the prior written consent of Aventis, which consent will not be unreasonably
withheld, conditioned or delayed. Upon Aventis' request TKT will provide a copy
of such sublicenses to Aventis.

            3.2.3 Exclusive Manufacturing Know-How License. Aventis hereby
grants to TKT a perpetual, exclusive and, except as provided below, royalty-free
right and license under Manufacturing Know-How (other than [**]) owned or
controlled by, or licensed (subject to the provisions of this subsection 3.2.3,
with the right to sublicense) to, Aventis prior to the Amendment Effective Date
to make and have made (subject to Section 3.2.5) GA-EPO throughout the world for
distribution and sale in the TKT Territory. With respect to Manufacturing
Know-How which has been licensed to Aventis by a Third Party, (i) TKT agrees
[**] with its sublicense of such Manufacturing Know-How, and (ii) if Aventis
does not currently have the right to sublicense such intellectual property to
TKT hereunder, such license is listed on Schedule 3.2.3 hereto and Aventis shall
use commercially reasonable efforts to obtain the right to sublicense such
intellectual property to TKT hereunder for such limited purposes.

            3.2.4 Sublicenses of Manufacturing Know-How. TKT shall have the
right to grant sublicenses under the Manufacturing Know-How license granted by
Aventis to TKT under subsection 3.2.3. TKT will provide a copy of such
sublicenses to Aventis if such sublicense covers the use of Aventis Technology.

                                      -8-
<PAGE>

            3.2.5 Right to Manufacture and Conduct Clinical Studies.

                  (a)   TKT shall not make or have made GA-EPO [**]. TKT shall
not conduct any clinical study in any country in the Aventis Territory without
the prior written consent of Aventis, which consent shall not be unreasonably
withheld, conditioned or delayed.

                  (b)   Aventis shall not make or have made GA-EPO [**]. Aventis
shall not conduct any clinical study in any country in the TKT Territory without
the prior written consent of TKT, which consent shall not be unreasonably
withheld, conditioned or delayed.

      3.3   Reservation of Rights.

            3.3.1 TKT Reservation. Notwithstanding the license grants set forth
above TKT at all times reserves the right under the TKT Patent Rights, TKT
Technology, and Manufacturing Know-How owned either exclusively by TKT or
jointly with Aventis (i) [**] and (ii) subject, with respect to Manufacturing
Know-How owned jointly by TKT and Aventis, to the consent of Aventis, which
consent shall not be unreasonably withheld, to make, have made, use, sublicense,
distribute for sale and sell products other than GA-EPO throughout the world.

            3.3.2 Aventis Reservation. Notwithstanding the license grants set
forth above, Aventis at all times reserves the right under the Aventis
Technology and Manufacturing Know-How owned either exclusively by Aventis or
jointly with TKT (i) [**] and (ii) subject, with respect to Manufacturing
Know-How owned jointly by TKT and Aventis, to the consent of TKT, which consent
shall not be unreasonably withheld, to research, develop, import, make, have
made, use, sublicense, distribute for sale and sell products other than GA-EPO
throughout the world.

      3.4   [**].

            3.4.1 Exclusive License. Aventis hereby grants to TKT an exclusive
(subject to Section 3.4.3), perpetual right and license under [**] (i) to [**];
and (ii) market, have marketed, offer for sale, sell, have sold, distribute,
have distributed and otherwise commercialize GA-EPO in the TKT Territory [**].

            3.4.2 Sublicense of [**]. TKT shall have the right to grant
sublicenses to [**] under the license granted by Aventis to TKT under this
Section 3.4 in each case in connection with the licensing by TKT of rights with
respect to GA-EPO; provided, however, that each such sublicense shall contain a
provision (i) requiring such sublicensee to [**] grant to Aventis a
non-exclusive, perpetual and royalty free sublicense to made, discovered or
developed by such sublicensee, and (ii) prohibiting further sublicensing of
[**]. In connection with such sublicenses, TKT may provide that the sublicensee
shall pay directly to Aventis any amounts which may become due in accordance
with Article 7; provided, however, that TKT shall in any event remain liable for
the payment of all such amounts notwithstanding any such provision between TKT

                                      -9-
<PAGE>

and its sublicensee. TKT shall provide a copy of any such sublicense to Aventis
promptly upon the execution thereof.

            3.4.3 Aventis Reservation of Rights. Aventis reserves the right to
practice [**] for any and all purposes other than [**].

      3.5   Oncology Data.

            3.5.1 Aventis has conducted clinical trials of GA-EPO for certain
oncology indications (the "Oncology Trials"). TKT may, at any time, request (a
"TKT License Request") a license to the data generated by Aventis in conducting
the Oncology Trials (the "Aventis Oncology Data"). Each TKT License Request will
include a description of TKT's proposed use (the "Proposed Use") of the Aventis
Oncology Data. Within thirty (30) days of its receipt of a TKT License Request,
Aventis shall notify TKT of its decision to accept or reject such TKT License
Request (which decision shall be in the sole discretion of Aventis). In the
event that Aventis accepts the TKT License Request, the Aventis Oncology Data
shall immediately become part of the Aventis Technology licensed to TKT
hereunder, and Aventis shall, as promptly as practicable, deliver copies of the
Aventis Oncology Data to TKT. If Aventis rejects such TKT License Request,
subject to Section 3.5.2, the Aventis Oncology Data will continue to be excluded
from the licenses granted by Aventis hereunder, and Aventis shall be under no
obligation to deliver copies of the Aventis Oncology Data to TKT.

            3.5.2 Upon the Aventis Determination Date, the Aventis Oncology Data
shall immediately become part of the Aventis Technology licensed to TKT
hereunder, and Aventis shall, as promptly as practicable, deliver copies of the
Aventis Oncology Data to TKT.

      3.6   Aventis Option. For a period of [**] from the Amendment Effective
Date, if TKT determines to sell or license to any Third Party (each, a "Gene
Therapy Transaction") any of TKT's gene therapy programs, including, but not
limited to, TKT's Factor VIII gene therapy program for hemophilia and GLP-1 gene
therapy program for diabetes, TKT shall first give Aventis a right of first
refusal to purchase or license, as the case may be, any such programs [**] (an
"Aventis Right of First Refusal"). At such time as TKT in good faith believes
that a Gene Therapy Transaction is likely to occur, TKT shall (i) provide
Aventis with notice that discussions with a Third Party are taking place (the
"Initial Notification"), (ii) provide Aventis with a summary of the proposed
terms of the transaction, (iii) provide Aventis with such information and
documentation as may be necessary for Aventis to make an informed determination
with regard to the rights granted under this Section 3.6, and (iv) respond to
all inquiries of Aventis related to the Gene Therapy Transaction, including but
not limited to requests for additional information regarding the gene therapy
program which is the focus of such Gene Therapy Transaction. Upon execution of a
term sheet between TKT and such third party, TKT shall provide such term sheet
to Aventis (the "Final Notification"), and Aventis shall have a period equal to
the longer of (A) [**] from the date of the Initial Notification and (B) [**]
from the date of the Final Notification, (the "Exercise Period") to notify TKT
of its intent to exercise the Aventis Right of First Refusal. If Aventis
provides TKT with

                                      -10-
<PAGE>

notice of its intent to exercise the Aventis Rights of First Refusal within the
Exercise Period, Aventis and TKT shall negotiate the terms of such sale or
license (as applicable) in good faith for a period of [**]. If Aventis does not
provide TKT with notice of its intent to exercise the Aventis Right of First
Refusal within the Exercise Period, or TKT and Aventis are unable to come to
terms regarding such sale or license within such [**] period, TKT shall be free
to enter into a Gene Therapy Transaction with such Third Party [**] the terms
and conditions contained in the final term sheet.

                                    ARTICLE 4

                               THE RESEARCH PHASE

      4.1   Conduct of the Research Program.

            4.1.1 General. The conduct of the Research Program shall be the
primary responsibility of TKT and shall take place primarily at TKT's facilities
in Cambridge, Massachusetts. The Research Program shall be conducted in good
scientific manner, and in compliance with all applicable good laboratory
practices and applicable legal requirements to achieve efficiently and
expeditiously its objectives. TKT shall proceed diligently with the work set out
in the Research Program using its best efforts using commercially reasonable
means consistent with those used by TKT for other projects with a similar
commercial potential.

            4.1.2 Research Plan. The Research Program shall be conducted under a
research plan which describes the work to be pursued by TKT during the Research
Phase and which has been approved by the R&D Oversight Committee prior to the
date hereof. If at any time during the Research Phase, TKT or Aventis determine
that a significant change to the research plan is necessary or desirable, it
shall prepare a written description detailing the change to the research plan
and shall submit such description to the R&D Oversight Committee for its
approval. An outline of the research plan is attached to the Original License
Agreement and describes the work to be pursued during the Research Phase,
including: (i) identifying the technical problems involved and the general
projects to be carried out regarding GA-EPO, (ii) estimating the personnel to be
committed for each project, and (iii) setting forth a projected timetable for
the work to be performed.

            4.1.3 Subcontracts. Subject to the approval of the R&D Oversight
Committee and the provisions of Article 9, TKT may subcontract portions of the
Research Program to be performed by it in the normal course of its business to a
Third Party.

            4.1.4 Data. TKT shall maintain records in sufficient detail and in
good scientific manner appropriate for regulatory filings and patent purposes
and as will properly reflect all work done and results achieved in the
performance of the Research Program (including all data in the form required to
be maintained under any applicable governmental regulations). Such records shall
include books, records, reports, research notes, charts, graphs, comments,
computations, analyses, recordings, photographs, computer programs and
documentation thereof, computer information storage means,

                                      -11-
<PAGE>

samples of materials and other graphic or written data generated in connection
with the Research Program. TKT shall provide Aventis the right to inspect such
records, and shall provide copies of all requested records, to the extent
reasonably required for the performance of Aventis's obligations under this
Agreement; provided, however, that Aventis shall maintain such records and the
information of TKT contained therein in confidence in accordance with Article 9
hereof and shall not use such records or information except to the extent
otherwise permitted by this Agreement.

            4.1.5 Quarterly Reports by TKT. Within fourteen (14) days following
the end of each calendar quarter, or at the reasonable request (with mutually
agreed advance notice) of the R&D Oversight Committee, TKT shall provide to the
members of the R&D Oversight Committee a written report which shall summarize in
reasonable detail the work TKT has performed under the Research Program during
the preceding calendar quarter.

            4.1.6 Assistance by Aventis. Aventis shall provide such assistance
to TKT in conducting the Research Program as TKT may reasonably request, and TKT
will reimburse Aventis for its documented Fully Absorbed Costs incurred in
providing such assistance; provided, however, that prior to providing such
assistance Aventis shall have provided to TKT an estimate of such Fully Absorbed
Costs and TKT shall have approved such estimate; provided, further, that no
failure of Aventis to undertake or successfully complete such assistance shall
relieve TKT from its obligations hereunder or affect Aventis's right to
terminate this Agreement pursuant to Section 12.3.

            4.1.7 Funding of the Research Program. TKT shall bear all costs and
expenses in connection with the Research Program.

      4.2   Term of the Research Phase.

            4.2.1 Completion of the Research Phase. The term of the Research
Phase shall commence as of the first day of the month following the Effective
Date. TKT shall deliver to the R&D Oversight Committee data characterizing the
cell line which is to be used to create the master cell bank, including the
history of the cell line, the growth properties of the cell line, the protocol
used to purify GA-EPO, the DNA sequence of plasmids used in generating the cell
line, erythropoietin expression levels, size, glycosylation profile, amino acid
composition, amino terminal sequence, an estimate of specific activity in vitro,
cDNA sequence, and site of plasmid integration and copy number. The R&D
Oversight Committee shall promptly evaluate the data submitted by TKT and
determine, in its reasonable discretion, whether such cell line can be used to
create a master cell bank which will yield a quantity of GA-EPO sufficient for
scale up to commercial production levels. The R&D Oversight Committee shall
provide TKT and Aventis with prompt written notice of its decision. Upon
notification of acceptance of such cell line by the R&D Oversight Committee, TKT
shall promptly deliver to Aventis such cell line which is to be used to create
the master cell bank, and Aventis shall have the right to use such cell line
consistent with the terms of this Agreement.

                                      -12-
<PAGE>

            4.2.2 Term of the Research Phase. The term of the Research Phase
shall continue until September 18, 1995.

                                    ARTICLE 5

                              THE DEVELOPMENT PHASE

      5.1   Conduct of the Development Phase.

            5.1.1 Development Phase. The Development Phase shall consist of the
preparation and filing of regulatory submissions and the preclinical and
clinical development of GA-EPO until, with respect to each country in the
Aventis Territory or TKT Territory, as the case may be, final marketing approval
for GA-EPO is obtained in such country.

            5.1.2 Development of GA-EPO in the TKT Territory. The conduct of the
Development Phase for regulatory approval in the TKT Territory shall be the sole
responsibility of, and shall be at the sole discretion of, TKT. All costs and
expenses of the Development Phase for regulatory approval in the TKT Territory
shall be borne exclusively by TKT.

            5.1.3 Development of GA-EPO in the Aventis Territory. The conduct of
the Development Phase for regulatory approval in the Aventis Territory shall be
the sole responsibility of, and, subject to Section 5.1.4, shall be at the sole
discretion of, Aventis. All costs and expenses associated with the Development
Phase for regulatory approval in the Aventis Territory shall be borne
exclusively by Aventis.

            5.1.4 Diligence Obligations. Promptly, but in no event more than
[**] following [**], Aventis shall notify TKT in writing (a "Determination
Notice") of its intention to either (i) continue) [**], or (ii) terminate this
Agreement pursuant to Section 12.4.2 (an "[**]"). The failure of Aventis to
deliver a Determination Notice to TKT within such [**] period shall be deemed an
[**].

      5.2   Development Information.

            5.2.1 Information for.

                  (a)   To the extent that such information or documentation has
not already been provided to Aventis in connection with Aventis' participation
on the Development Committee or R&D Oversight Committee, TKT will provide to
Aventis all documentation available to TKT which is reasonably required or
useful [**]. Without limiting the generality of the foregoing, to the extent
reasonably required or useful to Aventis, TKT shall provide Aventis with [**]
related to GA-EPO which Aventis may reasonably request and which is in the
possession of TKT. TKT shall have the right to redact any documents provided to
Aventis to remove information not related to GA-EPO. Aventis shall have the
right [**] but ownership of all such documentation (and any data contained in
such documentation) so conveyed shall remain vested in TKT.

                                      -13-
<PAGE>

                  (b)   To the extent that such information or documentation has
not already been provided to TKT in connection with TKT's participation on the
Development Committee or R&D Oversight Committee, Aventis will provide to TKT
all documentation available to Aventis which is reasonably required or useful
[**]. Without limiting the generality of the foregoing, to the extent reasonably
required or useful to TKT, Aventis shall provide TKT with [**] related to GA-EPO
which TKT may reasonably request and which is in the possession of Aventis.
Aventis shall have the right to redact any documents provided to TKT to remove
information not related to GA-EPO. TKT shall have the right to [**] but
ownership of all such documentation (and any data contained in such
documentation) so conveyed shall remain vested in Aventis.

            5.2.2 Regulatory Submissions.

                  (a)   To the extent that such documentation has not already
been provided by Aventis, Aventis shall provide TKT with copies of all
submissions to any drug regulatory authorities which have been made prior to the
Amendment Effective Date. To the extent that such documentation has already been
provided to TKT, Aventis shall, upon the request of TKT, use reasonable efforts
to provide copies of such documentation to TKT. Upon the reasonable request of
TKT, Aventis shall also provide TKT with copies of all submissions to drug
regulatory authorities in any country in the Aventis Territory and the results
of all clinical trials conducted by, or under the supervision of, Aventis with
respect to GA-EPO; provided, however, that Aventis reserves the right to assess
reasonable copying charges for any such materials requested by TKT which exceed
approximately two cartons of material.

                  (b)   Upon the reasonable request of Aventis, TKT shall
provide Aventis with copies of all submissions to drug regulatory authorities in
any country in the TKT Territory and the results of all clinical trials
conducted by, or under the supervision of, TKT with respect to GA-EPO; provided,
however, that TKT reserves the right to assess reasonable copying charges for
any such materials requested by Aventis which exceed approximately two cartons
of material.

                  (c)   TKT and Aventis shall use commercially reasonable
efforts to [**].

                                    ARTICLE 6

                RESEARCH, DEVELOPMENT AND REGULATORY COORDINATION

      6.1   R&D Oversight Committee.

            6.1.1 General. Promptly after the Effective Date, a joint committee
comprised of up to three named representatives of Aventis and up to three named
representatives of TKT (the "R&D Oversight Committee") shall be appointed. One
of the representatives of TKT shall act as Chairman of the R&D Oversight
Committee. The R&D Oversight Committee shall be responsible for the supervision
of the Research

                                      -14-
<PAGE>

Program. Such meetings shall be held at TKT's facilities located in Cambridge,
Massachusetts, and at such times as are agreed to by TKT and Aventis, or at such
other locations or in such other form (e.g., telephone or video conference) as
the members of the R&D Oversight Committee shall agree, but no less frequently
than three times per year. At such meetings, the principal function of the R&D
Oversight Committee will be to discuss the Research Program and determine
whether any cell line presented to it by TKT meets the specifications for
further development described in subsection 4.3.1. A party may change one or
more of its representatives to the R&D Oversight Committee at any time. Members
of the R&D Oversight Committee may be represented at any meeting by another
member of the R&D Oversight Committee so designated by the absent member, or by
a deputy. Any approval, determination or other action shall require the
affirmative vote of both TKT and Aventis, with each party having one vote, as
determined by each party's representatives who are members of the R&D Oversight
Committee. Employees, subcontractors or consultants of either TKT and Aventis
who are involved with the Program and who are not members of the R&D Oversight
Committee may attend meetings of the Committee as guests of either party.

            6.1.2 Minutes. The R&D Oversight Committee shall keep accurate
minutes of its deliberations. The Chairman shall be responsible for the
preparation of draft minutes. Draft minutes shall be sent to all members of the
R&D Oversight Committee within ten (10) business days after each meeting. All
records of the R&D Oversight Committee shall be available to both parties.

      6.2   Development Committee.

            6.2.1 General. Promptly after the Effective Date, a joint committee
comprised of up to four named representatives of Aventis and up to four named
representatives of TKT (the "Development Committee") shall be appointed. One of
the representatives of Aventis shall act as Chairman of the Development
Committee. Such meetings shall be held at TKT's facilities in Cambridge,
Massachusetts during the Research Phase, and thereafter in Bridgewater, N.J.,
and, in any event, at times and places or in such form (e.g., telephone or video
conference) as the members of the Development Committee shall agree but no less
frequently than three times per year. At such meetings, the Development
Committee will discuss the Development Phase of GA-EPO, including but not
limited to, preclinical and clinical testing and the preparation of regulatory
submissions for approval of GA-EPO in the Aventis Territory. To the extent
reasonable or appropriate, meetings of the Development Committee will be
coordinated and held jointly with the R&D Oversight Committee. A party may
change one or more of its representatives to the Development Committee at any
time. Members of the Development Committee may be represented at any meeting by
another member of the Development Committee so designated by the absent member,
or by a deputy. Notwithstanding the foregoing, after the Amendment Effective
Date, the provisions of this Agreement relating to the obligations and
activities of the Development Committee shall be suspended until the date of an
Aventis Positive Notification.

      6.3   Minutes. The Development Committee shall keep accurate minutes of
its deliberations. The Chairman shall be responsible for the preparation of
draft minutes.

                                      -15-
<PAGE>

Draft minutes shall be sent to all members of the Development Committee within
ten (10) business days after each meeting. All records of the Development
Committee shall at all times be available to both parties.

      6.4   General Disagreements. All disagreements within the R&D Oversight
Committee and the Development Committee shall be resolved in accordance with the
provisions of Section 13.6.

      6.5   Visit of Facilities. Representatives of Aventis may, upon reasonable
notice and at times reasonably acceptable to TKT, visit TKT's facilities where
the Research Program is being conducted and consult with personnel of TKT
performing work on the Research Program, and those of any permitted
subcontractors of TKT. Representatives of TKT and Aventis may, with the other
party's prior approval, which approval shall not be unreasonably withheld, visit
manufacturing sites and the sites of any clinical trials or other experiments
being conducted by such other party in connection with the Development Phase. If
requested by the other party, TKT and Aventis shall cause appropriate
individuals working on the Development Phase to be available for meetings at the
location of the facilities where such individuals are employed at times
reasonably convenient to the party responding to such request.

      6.6   Review and Planning.

            6.6.1 Clinical, Regulatory and Marketing Activities. Representatives
of TKT (and its sublicensees) and Aventis (and its sublicensees) shall meet from
time to time as may be determined between the parties, but in no event less
frequently than annually, at a place mutually agreed to by the parties (which,
prior to the First Commercial Sale, will be one of the R&D Oversight Committee
or Development Committee meetings) (each, a "CRM Meeting"). At each CRM Meeting
each party shall review the clinical, regulatory and marketing activities
undertaken by the other party or its Affiliates since the previous CRM Meeting
and shall present its clinical, regulatory and marketing plans for GA-EPO for
the ensuing year. Each party will consider in good faith the clinical,
regulatory and marketing plans of the other party for GA-EPO for the ensuing
year; provided, however, that neither party will be required to take any action
to modify its clinical, regulatory or marketing plans based upon the plans of
the other party. Notwithstanding the foregoing, no CRM Meeting will be held
prior to an Aventis Positive Notification.

            6.6.2 Chemistry, Manufacturing and Controls Activities.
Representatives of TKT (and its sublicensees), Aventis (and its sublicensees)
and [**] shall meet from time to time as may be determined between the Aventis
and TKT, but in no event less frequently than quarterly, at a place mutually
agreed to by the parties (each, a "CMC Meeting"). At each CMC Meeting the
parties shall review the chemistry, manufacturing and controls ("CMC")
activities of TKT and Aventis (and their respective sublicensees) since the
previous CMC Meeting, each of TKT and Aventis shall present its CMC plans for
GA-EPO for the ensuing quarter, and the parties shall discuss any proposed
material changes to the specifications of GA-EPO, the manufacturing
specifications or the quality control processes related to the manufacture and
release of

                                      -16-
<PAGE>

GA-EPO. Each of Aventis and TKT will consider in good faith the CMC plans of the
other party for GA-EPO for the ensuing year; provided, however, that neither
Aventis nor TKT will be required to take any action to modify its CMC plans
based upon the CMC plans of the other party.

            6.6.3 Responsibility. After the Amendment Effective Date, Aventis
shall be responsible, subject to Section 5.1.4, for all clinical, regulatory,
marketing and CMC activities related to the research, development, manufacture,
distribution or sale of GA-EPO by Aventis, its Affiliates or sublicensees in the
Aventis Territory, and TKT shall be responsible for all clinical, regulatory,
marketing and CMC activities related to the research, development, manufacture,
distribution or sale of GA-EPO by TKT, its Affiliates or sublicensees in the TKT
Territory.

      6.7   Regulatory Matters.

            6.7.1 Adverse Event Reporting. Aventis and TKT shall each: (a)
notify the other of each Serious Adverse Drug Experience with respect to GA-EPO
within forty-eight (48) hours of the time such Serious Adverse Drug Experience
becomes known to such party or an Affiliate of such party; and (b) notify the
other of each Adverse Drug Experience with respect to GA-EPO within two (2)
business days of the time such Adverse Drug Experience becomes known to such
party or an Affiliate of such party. For purposes of this Section 6.6: (a) an
"Adverse Drug Experience" shall mean any "adverse experience" as defined or
contemplated by 21 C.F.R. 312.32 or 314.80; and (b) a "Serious Adverse Drug
Experience" shall mean any "Adverse Drug Experience" that is fatal or life
threatening, is permanently disabling, requires in-patient hospitalization, or
is a congenital anomaly, cancer or overdose, or any other event which would
constitute a "serious adverse drug experience" pursuant to the terms of 21 C.F.R
312.32 or 314.80.

            6.7.2 Communication with Regulatory Authorities. TKT shall not,
without the prior written consent of Aventis, or unless required by applicable
law, correspond or communicate with the FDA or with any other regulatory
authority in the Aventis Territory regarding GA-EPO. Furthermore, TKT shall,
immediately upon receipt of any communication from the FDA or from any other
regulatory authority in the Aventis Territory regarding GA-EPO, forward a copy
or description (if not in writing) of such communication to Aventis, and respond
to all inquiries of Aventis relating thereto. If TKT is advised by its legal
counsel that it must communicate with the FDA or with any other regulatory
authority in the Aventis Territory regarding GA-EPO, then TKT shall so advise
Aventis immediately and, unless applicable law prohibits, provide Aventis in
advance with a copy or description of any proposed communication with the FDA or
any other regulatory authority in the Aventis Territory regarding GA-EPO and
comply with any and all reasonable direction of Aventis concerning any meeting
or written or oral communication with the FDA or any other regulatory authority
in the Aventis Territory regarding GA-EPO.

            6.7.3 Communication with Regulatory Authorities. Aventis shall not,
without the prior written consent of TKT, or unless required by applicable law,
correspond or communicate with any regulatory authority in the TKT Territory
regarding

                                      -17-
<PAGE>

GA-EPO. Furthermore, Aventis shall, immediately upon receipt of any
communication from any regulatory authority in the TKT Territory regarding
GA-EPO, forward a copy or description (if not in writing) of such communication
to TKT, and respond to all inquiries of TKT relating thereto. If Aventis is
advised by its legal counsel that it must communicate with any regulatory
authority in the TKT Territory regarding GA-EPO, then Aventis shall so advise
TKT immediately and, unless applicable law prohibits, provide TKT in advance
with a copy or description of any proposed communication with such regulatory
authority in the TKT Territory regarding GA-EPO and comply with any and all
reasonable direction of TKT concerning any meeting or written or oral
communication with such regulatory authority in the TKT Territory regarding
GA-EPO.

      6.8   [**].

                                    ARTICLE 7

                            MILESTONES AND ROYALTIES

      7.1   Milestone Payments. Aventis and TKT acknowledge payment by Aventis
to TKT of $[**] contemporaneously with the signing of a Letter Agreement dated
March 18, 1994 between TKT and Aventis. In consideration of TKT's work on the
Research Program and the licenses granted to Aventis hereunder, Aventis has paid
or shall pay the following additional amounts to TKT upon the achievement of
each of the following milestones (except as noted below), prior to any
expiration or termination of this Agreement under Article 12 with respect to the
country to which such milestone relates, it being understood and agreed to that
TKT shall use a portion of such payments as necessary to fund the performance of
its obligations under the Program:

<TABLE>
<CAPTION>
                       Milestone                                        Payment
                       ---------                                        -------
<S>                                                        <C>
Execution of the Original License Agreement                $[**] (Paid)

                                                           $5,000,000 Preferred Stock
                                                           Investment(1) (Paid)

Initial Public Offering (as defined in the Class D Stock   $5,000,000 Common Stock
Purchase Agreement) ("IPO") by TKT                         Investment(Paid)

                                                           Additional $5,000,000 Common Stock
                                                           Investment (2)(Paid)

First Approval of Cell Line by R&D Oversight Committee     $[**] (Paid)

First Filing of IND with the FDA                           $[**] (Paid)

Start of Phase III Clinical Trials                         $[**] (Paid)

First Filing of BLA with the FDA                           $[**] (Paid)

First Commercial Sale in the United States                 $[**]
</TABLE>

                                      -18-
<PAGE>

(1)   On the terms and subject to the conditions of the Class D Preferred Stock
      Purchase Agreement dated as of May 18, 1994, by and between Aventis and
      TKT (the "Class D Stock Purchase Agreement").

(2)   Aventis shall purchase shares Common Stock of TKT in the IPO upon the
      terms and subject to the conditions of the Class D Stock Purchase
      Agreement.

      Either TKT or Aventis shall notify the other in writing within ten (10)
business days following the occurrence of each of the milestones set forth
above. Within ten (10) business days after receipt of such notice, Aventis shall
pay to TKT in United States dollars by check or other means acceptable to TKT,
the milestone payments set forth above. Milestone payments made to TKT pursuant
to this Section 7.1 are not refundable under any circumstances and will not be
credited against royalty payments due TKT under Section 7.2.

      7.2   Royalties. The Selling Party shall pay to the other party royalties
as follows:

            7.2.1 Royalties to TKT Based on Net Sales of GA-EPO. Except as
otherwise provided in this Section 7.2, Aventis shall pay to TKT a royalty based
on the Net Sales of GA-EPO covered by the TKT Patent Rights or which uses the
TKT Technology in the Aventis Territory, from the launch of sales in such
territory until the expiration of the royalty obligations of Aventis under
Section 12.2, at the rates set forth below:

<TABLE>
<CAPTION>
   Cumulative Net Sales of GA-EPO in the            Royalty Rate as a
Applicable Territory in Millions of Dollars           % Net Sales
-------------------------------------------           -----------
<S>                                                 <C>
Equal to or less than $[**]                               [**]%
Over $[**]                                                [**]%
</TABLE>

it being understood that the [**]% rate starts at the first dollar over $[**]
million. -

7.2.2 Royalties to Aventis Based on Net Sales of GA-EPO. Except as otherwise
provided in this Section 7.2, TKT shall pay to Aventis a royalty based on the
Net Sales of GA-EPO covered by the TKT Patent Rights or which uses the TKT
Technology or Aventis Technology in the TKT Territory, from the launch of sales
in such territory until the expiration of the royalty obligations of TKT under
Section 12.3 (i), at the rates set forth below:

<TABLE>
<CAPTION>
       Annual Net Sales of GA-EPO in the                  Royalty Rate as a
  Applicable Territory in Millions of Dollars                % Net Sales
  -------------------------------------------                -----------
<S>                                                       <C>
Equal to or less than $[**]                                     [**]%
More than $[**] and equal to or less than $[**]                 [**]%
More than $[**] and equal to or less than $[**]                 [**]%
Over $[**]                                                      [**]%
</TABLE>

                                      -19-
<PAGE>

it being understood that the increased percentage rate starts at the first
dollar over each Net Sales threshold.

            7.2.3 Sharing of Revenues From Sublicensees. If TKT grants one or
more sublicenses to research, develop, make, have made, distribute, sell or have
sold GA-EPO to any Third Parties, at such point as TKT has received an aggregate
of $[**] in up-front and milestone payments under such sublicenses, TKT shall
pay to Aventis [**] percent ([**]%) of any incremental up-front and/or milestone
payments in excess of $[**] received by TKT from such sublicensees.
Notwithstanding anything else in this Section 7.2.3, Aventis shall have no right
to receive any payment from TKT as a result of (i) TKT selling securities,
including common stock of TKT, to a third party in connection with a sublicense
or (ii) any sublicense to (A) research, develop, make or have made GA-EPO for
distribution and sale in Japan, or (B) distribute, sell or have sold GA-EPO in
Japan.

      7.3   Royalties Based on Net Sales of [**]. TKT shall pay to Aventis a
royalty based on the Net Sales of [**] in the TKT Territory, from the launch of
sales in such territory until the expiration of the royalty obligations of TKT
under Section 12.3(ii), at the rates set forth below:

<TABLE>
<CAPTION>
        Annual Net Sales of [**] in the                    Royalty Rate as a
  Applicable Territory in Millions of Dollars                 % Net Sales
  -------------------------------------------                 -----------
<S>                                                        <C>
Equal to or less than $[**]                                      [**]%
More than $[**] and equal to or less than $[**]                  [**]%
More than $[**]                                                  [**]%
</TABLE>

it being understood that the increased percentage rate starts at the first
dollar over each Net Sales threshold. The royalties owed to Aventis by TKT
pursuant to this Section 7.3 are in addition to, and not in lieu of, any royalty
owed to Aventis by TKT pursuant to Section 7.2 hereof.

      7.4   Royalty Reports, Exchange Rates. (a) During the term of this
Agreement, following the First Commercial Sale of GA-EPO covered by the TKT
Patent Rights or which uses the TKT Technology by the Selling Party in the
Applicable Territory, the Selling Party shall furnish to the other party a
written quarterly report showing with respect to GA-EPO covered by the TKT
Patent Rights or which use the TKT Technology, on a country by country basis
(except as provided below): (i) the gross sales of all GA-EPO covered by the TKT
Patent Rights or which uses the TKT Technology sold by the Selling Party and its
Affiliates, its distributors and its permitted sublicensees, during the
reporting period; (ii) the calculation of Net Sales from such gross sales; (iii)
any revenues from sublicensees received by such Selling Party during the
reporting period; (iv) the royalties and other payments payable in United States
dollars which shall have accrued hereunder in respect of such Net Sales and
sublicense revenue; (v) withholding taxes, if any, required by law to be
deducted as a payment by the other party in respect of such Net Sales and
sublicense revenue; and (vi) the exchange rates used in

                                      -20-
<PAGE>

determining the amount of United States dollars. In addition, TKT shall furnish
to Aventis written quarterly reports in accordance with the foregoing with
respect to Net Sales of [**].

      (b)   With respect to sales of GA-EPO invoiced in United States dollars,
the Net Sales amounts and the amounts due hereunder shall be expressed in United
States dollars. With respect to sales of GA-EPO invoiced in a currency other
than United States dollars, the Net Sales and amounts due hereunder shall be
expressed in the domestic currency of the party making the sale, together with
the United States dollar equivalent of the amount payable, calculated using the
arithmetic average of the exchange rates certified by the Federal Reserve Bank
of New York for customs purposes on each Business Day of each month of the
calendar quarter in which the Net Sales were made. The "exchange rates certified
by the Federal Reserve Bank of New York for customs purposes" found at
http://www.federalreserve.gov/releases/h10/Hist/ or any other publication as
agreed to by the parties shall be used as the source of exchange rates to
calculate the average as defined in the preceding sentence.

      7.5   Audits.

            7.5.1 Procedure. Upon the written request of TKT or Aventis, the
other party shall permit an internal auditor or independent public accountant
selected by TKT or Aventis, as the case may be, and acceptable to the other
party, which acceptance shall not be unreasonably withheld, to have access
during normal business hours to such of the records of Aventis or TKT, as the
case may be, as may be reasonably necessary to verify the accuracy of the
royalty reports, cost computations and final cost amounts described hereunder,
in respect of any fiscal year ending not more than twenty-hour (24) months prior
to the date of such request. All such verifications shall be conducted at TKT's
or Aventis's, as the case may be, expense and not more than once in each
calendar year.

            7.5.2 Expenses. In the event such accountant concludes that
additional royalties or lower expense reimbursement were required during such
period, and the party receiving such audit request agrees with such conclusion,
the additional royalty shall be paid in accordance with Section 7.5 or the
excess expense reimbursement shall be promptly repaid. The fees charged by such
accountant shall be paid by the party requesting such audit, unless the audit
discloses and the party receiving such audit request agrees (i) in the case of
an audit by TKT, that the royalties payable by Aventis, or, (ii) in the case of
an audit by Aventis, that the cost computation estimates and final amounts
hereunder, for the audited period are incorrect by more than five percent (5%),
in which case the audited party shall pay the reasonable fees and expenses
charged by the accountant.

            7.5.3 Sublicenses.

                  (a)   Aventis shall use reasonable efforts to include in each
Third Party sublicense granted by it pursuant to this Agreement a provision
requiring the sublicensee to make reports to Aventis, to keep and maintain
records of sales made pursuant to such sublicense and to grant access to such
records by TKT's independent

                                      -21-
<PAGE>

accountant to the same extent required of Aventis under this Agreement. Upon the
expiration of twenty-four (24) months following the end of any fiscal year, the
calculations of royalties payable with respect to such year shall be binding and
conclusive upon TKT; and Aventis and its sublicensees shall be released from any
liability of accountability with respect to royalties for such year.

                  (b)   TKT shall use reasonable efforts to include in each
Third Party sublicense granted by it pursuant to this Agreement a provision
requiring the sublicensee to make reports to TKT, to keep and maintain records
of sales made pursuant to such sublicense and to grant access to such records by
Aventis' independent accountant to the same extent required of TKT under this
Agreement. Upon the expiration of twenty-four (24) months following the end of
any fiscal year, the calculations of royalties payable with respect to such year
shall be binding and conclusive upon Aventis; and TKT and its sublicensees shall
be released from any liability of accountability with respect to royalties for
such year.

            7.5.4 Confidential Treatment. Each party agrees that all information
subject to review under this Section 7.5 or under any sublicense agreement is
confidential and that such party shall cause its accountant to retain all such
information in confidence.

      7.6   Royalty Payment Terms. Royalties shown to have accrued by each
royalty report provided for under this Agreement shall be due and payable on the
date such royalty report is due. Payment of royalties in whole or in part may be
made in advance of such due date. Royalties determined to be owing, and any
overpayments to be credited, with respect to any prior quarter shall be added or
credited, as the case may be, to the next quarterly payment hereunder.

      7.7   Form of Payment. All research payments, milestone payments,
royalties and other payments due hereunder shall be paid in United States
dollars. If at any time legal restrictions prevent the prompt remittance of part
or all royalties with respect to any country of the Aventis Territory or TKT
Territory, as the case may be, where GA-EPO covered by the TKT Patent Rights or
TKT Technology or Aventis Technology is sold, payment shall be made through such
lawful means or methods as the non-Selling party may determine.

      7.8   Withholding Taxes.

            7.8.1 All royalties payable to TKT hereunder shall be paid without
deductions of any withholding taxes, value-added taxes or other taxes, levies or
charges applicable to such payments, other than (i) United States taxes payable
by TKT and (ii) foreign taxes payable by TKT to the extent that such taxes are
imposed by reason of TKT's having a permanent establishment in any country
within the Aventis Territory or otherwise being subject to taxation by such
country (except foreign taxes imposed solely by reason of the license granted to
Aventis hereunder). Aventis shall be credited for the net benefit realized by
TKT for any foreign tax deductions or credits taken by TKT with respect to such
amounts paid by Aventis. In addition, any reorganization of TKT or an Affiliate
of TKT with or into an entity organized outside the United States shall not
result

                                      -22-
<PAGE>

in any increased costs to Aventis under this Agreement. Each party will assist
the other party in claming tax refunds, deductions or credits at the other
party's request and will cooperate to minimize the withholding tax, if
available, under various treaties applicable to any payment made hereunder.

            7.8.2 All royalties payable to Aventis hereunder shall be paid
without deductions of any withholding taxes, value-added taxes or other taxes,
levies or charges applicable to such payments, other than (i) United States
taxes payable by Aventis and (ii) foreign taxes payable by Aventis to the extent
that such taxes are imposed by reason of Aventis' having a permanent
establishment in any country within the TKT Territory or otherwise being subject
to taxation by such country (except foreign taxes imposed solely by reason of
the license granted to TKT hereunder). TKT shall be credited for the net benefit
realized by Aventis for any foreign tax deductions or credits taken by Aventis
with respect to such amounts paid by TKT. In addition, any reorganization of
Aventis or an Affiliate of Aventis with or into an entity organized outside the
United States shall not result in any increased costs to TKT under this
Agreement. Each party will assist the other party in claming tax refunds,
deductions or credits at the other party's request and will cooperate to
minimize the withholding tax, if available, under various treaties applicable to
any payment made hereunder.

      7.9   Interest on Late Payments. Any payments by either party that are not
paid on or before the date such payments are due under this Agreement shall bear
interest, to the extent permitted by law, at the London Interbank Offering Rate
as set by Citibank, N.A. from time to time, plus 50 basis points, calculated on
the number of days payment is delinquent.

                                    ARTICLE 8

                          INTELLECTUAL PROPERTY RIGHTS

      8.1   Ownership.

            8.1.1 Ownership of Discoveries and Improvements. All right, title
and interest in all writings, inventions, discoveries, improvements and other
technology, whether or not patentable or copyrightable, and any patent
applications, patents or copyrights based thereon (collectively, the
"Inventions") that are discovered, made or conceived during and as a result of
the Research Phase or the Development Phase solely by employees of TKT or others
acting on behalf of TKT ("TKT Inventions") shall be owned by TKT. In addition,
TKT shall retain ownership of, and shall be responsible for maintaining and
protecting, the cell line approved by the R&D Oversight Committee pursuant to
subsection 4.3.1 which is used to create the master cell bank; provided that,
TKT will provide Aventis with access to such cell line to create a new master
cell bank in the event that the master cell bank in Aventis's possession is
destroyed or otherwise rendered unusable. All right, title and interest in all
inventions that are discovered, made or conceived during and as a result of the
Research Phase or the Development Phase or thereafter solely by employees of
Aventis or others acting on behalf of Aventis ("Aventis Inventions") shall be
owned by Aventis. All right, title and interest in all Inventions that

                                      -23-
<PAGE>

are discovered, made or conceived during and as a result of the Research Phase
or the Development Phase or thereafter jointly by employees of TKT and Aventis
or others acting on their behalf (the "Joint Inventions") shall be jointly owned
by Aventis and TKT. Each party shall promptly disclose to the other party the
making, conception or reduction to practice of Inventions by employees or others
acting on behalf of such party. The parties acknowledge that the ownership
rights set forth above are subject to the license grants set forth in Article 3.

            8.1.2 Cooperation of Employees. Each party represents and agrees
that its employees and consultants shall be obligated under a binding written
agreement to assign to such party, or as such party shall direct, all Inventions
made or conceived during and as a result of the Research Phase or the
Development Phase by such employee or consultant. In the case of non-employees
working for other companies or institutions on behalf of TKT or Aventis, TKT or
Aventis, as applicable, shall use reasonable efforts to obtain the right to
license all Inventions made by such non-employees on behalf of TKT or Aventis,
as applicable, in accordance with the policies of the company or institution
employing such non-employee. TKT and Aventis agree to undertake to enforce such
agreements with employees or others or such rights pertaining to non-employees
(including, where appropriate, by legal action) considering, among other things,
the commercial value of such Inventions.

      8.2   Filing, Prosecution and Maintenance of TKT Patent Rights and TKT
Technology.

            8.2.1 Filing, Prosecution and Maintenance. TKT shall be responsible
for the filing, prosecution (including oppositions) and maintenance of all
patent applications and patents which make up the TKT Patent Rights and such
other registrations related to the TKT Technology. For so long as any of the
license grants set forth in Article 3 remain in effect, TKT agrees to file and
prosecute patent applications and maintain the patents covering the TKT Patent
Rights and, to the extent applicable, for the registration or other protection
of the TKT Technology, in all countries in the Aventis Territory in which
Aventis customarily files for products of similar interest. TKT shall consult
with Aventis and keep Aventis fully informed of important issues relating to the
preparation, filing, prosecution and maintenance of such patent applications and
patents, including patent strategy with respect to both existing and future
patent applications, patents and patent extensions, and shall furnish to Aventis
copies of documents relevant to such preparation, filing, prosecution or
maintenance sufficiently prior to filing such document or making any payment due
thereunder to allow for review and comment by Aventis, and TKT shall seriously
consider all such comments. TKT and Aventis shall mutually determine procedures
for carrying out the filing, prosecution (including oppositions) and
maintenance, as applicable, of patent applications and patents for all Joint
Inventions and shall each bear half of the costs thereof, and both parties shall
be kept fully informed of and consult and cooperate with respect to all actions
taken with respect thereto; provided that, if either party elects to not bear
half the cost of such activity with respect to a particular Joint Invention in a
particular country, then the other party may, at its sole expense and
discretion, undertake the filing, prosecution (including oppositions) and
maintenance of such patent or patent application in such country, and the party
not

                                      -24-
<PAGE>

participating in such expenses shall assign its interest in such patent or
patent application in such country to the other party, including the rights to
receive and collect from third parties any royalties and damages from future or
past infringement, but reserving a perpetual royalty-free non-exclusive license
in such country (without the right to sublicense and subject to any limitations
imposed by this Agreement, including Section 2.2 hereof) to use such Joint
Invention to make, have made, use, distribute for sale and sell any products
covered by such patent covering such Joint Invention. The non-participating
party will cooperate with the other party, at the other party's expense, as
necessary to enable the other party to establish and protect its rights under
this subsection 8.2.1.

      If TKT elects not to continue to seek or maintain patent protection on any
patent or patent application which makes up the TKT Patent Rights or relates to
the TKT Technology in any country, Aventis shall have the right, at its option,
but in the name of TKT and at TKT's expense, to file, prosecute (including
oppositions) and maintain such patent applications and patents as TKT shall have
previously filed in at least one country, provided, however, that the rights of
the parties with respect to any such TKT Patent Rights and TKT Technology shall
in all other respects be as described in this Agreement. TKT will advise Aventis
of all decisions taken with respect to any such election in a timely manner in
order to allow Aventis to protect its rights under this subsection 8.2.1.

            8.2.2 Patent Filing Costs. TKT shall bear all costs associated with
filing, prosecuting and maintaining patent applications and patents covering the
TKT Patent Rights in all countries in the Aventis Territory.

      8.3   Cooperation. Each party shall make available to the other party (or
to the other party's authorized attorneys, agents or representatives), its
employees, agents, subcontractors or consultants to the extent reasonably
necessary or appropriate to enable the appropriate party to file, prosecute and
maintain patent applications and resulting patents with respect to Inventions
owned by a party and for periods of time reasonably sufficient for such party to
obtain the assistance it needs from such personnel. Where appropriate, each
party shall sign or cause to have signed all documents relating to said patent
applications or patents at no charge to the other party. Notwithstanding the
foregoing, Aventis shall not be precluded from contesting the validity or
enforceability of the TKT Patent Rights or TKT Technology.

      8.4   Notification of Patent Term Restoration. TKT shall notify Aventis of
(i) the issuance of each patent included within the TKT Patent Rights, giving
the date of issue and patent number for each such patent, and (ii) each notice
pertaining to any patent included within the TKT Patent Rights which it receives
as patent owner pursuant to the Drug Price Competition and Patent Term
Restoration Act of 1984 (hereinafter called the "Act"), or other similar laws
now or hereafter in effect, or pursuant to comparable laws or regulations in
other countries in the Aventis Territory. The parties shall cooperate with each
other in applying for patent term extensions (including Supplementary Protection
Certificates in European Community Countries) where applicable in any country of
the Aventis territory. TKT shall also notify Aventis of each application filed
for patent term extension, any allegations of failure to show due diligence and
all awards of patent term

                                      -25-
<PAGE>

extensions with respect to the TKT Patent Rights. Such notices shall be given
promptly, but in any event within ten (10) business days after receipt of each
such notice pursuant to the Act (or comparable laws or regulations in other
countries in the Aventis Territory). TKT shall notify Aventis of each filing for
patent term restoration under the Act (or comparable laws or regulations in
other countries in the Aventis Territory), any allegations of failure to show
due diligence and all awards of patent term restoration (extensions) with
respect to the TKT Patent Rights.

      8.5   No Other Technology Rights. Except as otherwise expressly provided
in this Agreement, under no circumstances shall a party hereto, as a result of
this Agreement, obtain any ownership interest in or other right to any
technology, know-how, patents, pending patent applications, products, or
biological materials of the other party, including items owned, controlled or
developed by the other party, or transferred by the other party to said party,
at any time pursuant to this Agreement. It is understood and agreed that this
Agreement does not grant Aventis any license or other right in the TKT Patent
Rights for uses other than the production, manufacture, use, distribution for
sale and sale of GA-ERPO covered by the TKT Patent Rights or which uses the TKT
Technology. It is understood and agreed that this Agreement does not grant TKT
any license or other right in the [**] for uses other than the for sale and
distribution in the TKT Territory.

      8.6   Enforcement of TKT Patent Rights and TKT Technology; Defense of
Infringement Actions. TKT and Aventis shall each promptly, but in any event no
later than ten (10) business days after receipt of notice of such action, notify
the other in writing of any patent nullity actions, any declaratory judgment
actions or any alleged or threatened infringement of patents or patent
applications or misappropriation of intellectual property comprising the TKT
Patent Rights or the TKT Technology or if either party, or any of their
respective Affiliates, shall be individually named as a defendant in a legal
proceeding by a Third Party alleging infringement of a patent or other
intellectual property right as a result of the manufacture, production, use,
distribution for sale or sale of GA-EPO, or of any other information or
notification regarding the TKT Patent Rights or TKT Technology.

            8.6.1 First Right to Respond.

                  (a)   Aventis's First Right to Respond. Aventis shall have the
first right to respond to, defend or prosecute any actions, challenges,
infringements, misappropriations or proceeding by a Third Party alleging
infringement described in Section 8.6.1 brought in the Aventis Territory or
alleging infringement based upon the manufacture, production, use, distribution
for sale or sale of GA-EPO in the Aventis Territory. In the event Aventis elects
to do so, TKT will cooperate with Aventis and its legal counsel, join in such
suits as may be brought by Aventis, and be available at Aventis's reasonable
request to be an expert witness or otherwise to assist in such proceedings.
Aventis will cooperate with TKT and its legal counsel and keep TKT and its
counsel reasonably informed at all times as to the status of Aventis's response
or defense.

                                      -26-
<PAGE>

                  (b)   TKT's First Right to Respond. TKT shall have the first
right to respond to, defend or prosecute any actions, challenges, infringements,
misappropriations or proceedings brought by a Third Party alleging infringement
described in Section 8.6 brought in the TKT Territory or alleging infringement
based upon the manufacture, production, use, distribution for sale or sale of
GA-EPO in the TKT Territory. In event that TKT elects to do so, Aventis will
cooperate with TKT and its legal counsel, join in such suits as may be brought
by TKT, and be available at TKT's reasonable request to be an expert witness or
otherwise assist in such proceedings. TKT will cooperate with Aventis and its
legal counsel and keep Aventis and its counsel reasonably informed at all times
as to the status of TKT's response or defense.

            8.6.2 No Adverse Settlement Without Consent.

                  (a)   No Adverse Settlement Without TKT Consent. Aventis will
not settle any suit involving the TKT Patent Rights or TKT Technology in a
manner that would compromise any rights of TKT without obtaining the prior
written consent of TKT.

                  (b)   No Adverse Settlement Without Aventis Consent. TKT will
not settle any suit involving the TKT Patent Rights or TKT Technology in a
manner that would compromise any rights of Aventis without obtaining the prior
written consent of Aventis.

            8.6.3 Sharing of Litigation and Settlement Expenses.

                  (a)   On-going Litigation. Each party acknowledges and agrees
that Aventis has responded to certain patent infringement actions brought by
Amgen, Inc. and Kirin-Amgen, Inc. in the United States (the "U.S. Amgen Patent
Litigation") and in Europe (the "European Amgen Patent Litigation") (such
continuing litigation identified by Action Numbers: (a) 97-10814-WGY; (b)
4547/2002; and (c) HC01C03284.

                        (i)   After the Amendment Effective Date, Aventis shall
retain the right to control the U.S. Amgen Patent Litigation. Aventis shall be
responsible for [**]% of any legal fees and other costs and expenses associated
with the U.S. Amgen Patent Litigation incurred prior to the Amendment Effective
Date. After the Amendment Effective Date, (A) legal fees and other costs and
expenses associated with the U.S. Amgen Patent Litigation, including, but not
limited to any costs incurred in connection with settlements (subject to (B)
below), court awards, judgments or other damages arising from such litigation,
and those costs incurred by TKT at Aventis's request, shall be shared [**]% by
Aventis and [**]% by TKT; (B) costs of acquiring Third Party patents or licenses
in connection with U.S. Amgen Patent Litigation shall be shared [**]% by Aventis
and [**]% by TKT; and (C) amounts recovered from Third Parties in connection
with the U.S. Amgen Patent Litigation shall (w) first belong [**]% to Aventis
until Aventis has recovered the costs incurred in connection with the U.S. Amgen
Patent Litigation (including costs advanced to TKT which have not been recovered
by Aventis), (x) then belong [**]% to TKT until TKT has recovered all costs
actually paid by TKT in connection with the U.S. Amgen Patent Litigation, and
(y) then shall be shared [**]% to

                                      -27-
<PAGE>

Aventis and [**]% to TKT. Aventis shall advance all costs required to be paid by
TKT pursuant to clauses (A) and (B), and shall recover advanced costs through
credits against up to [**] percent ([**]%) of the royalties otherwise payable by
Aventis to TKT hereunder, until the amount so advanced by Aventis is fully
recovered; provided, however, in the event that the rights of Aventis to sell
GA-EPO in the Aventis Territory are terminated, or the sale of GA-EPO covered by
the TKT Patent Rights or which uses the TKT Technology is permanently enjoined
in any country or countries in the Aventis Territory accounting for
substantially all of the Net Sales of GA-EPO covered by the TKT Patent Rights or
which uses the TKT Technology by Aventis at a time when Aventis has not
recovered all of the costs advanced by Aventis for legal fees and other costs
and expenses associated with such response or defense incurred after the
Amendment Effective Date, then TKT shall pay to Aventis the portion of such
costs not so recovered by Aventis within ninety (90) days after the occurrence
of such termination or injunction. In order to allow TKT to comply with any
applicable financial reporting requirements, Aventis and TKT shall cooperate in
causing Fish & Neave, or its successor, to, within ten (10) days of the end of
each calendar quarter, provide Aventis and TKT with a summary of all litigation
costs incurred in such calendar quarter. Notwithstanding the foregoing, TKT's
obligations pursuant to this Section 8.6.3(i)(A), either directly or through
deduction from royalties owed to TKT, shall not exceed $[**]; provided, however,
that in the event that [**].

                        (ii)  After the Amendment Effective Date, TKT shall
control the European Amgen Patent Litigation. Aventis shall be responsible for
[**]% of any legal fees and other costs and expenses associated with the
European Amgen Patent Litigation incurred prior to the Amendment Effective Date.
After the Amendment Effective Date: (A) legal fees and other costs and expenses
associated with the European Amgen Patent Litigation, including those incurred
by Aventis at TKT's request, shall be borne [**]% by TKT; (B) costs of acquiring
Third Party patents or licenses and any settlement, court award, judgment or
other damages will be borne [**]% by TKT; and (C) amounts recovered from Third
Parties in connection with the European Amgen Patent Litigation shall belong
[**]% to TKT. Notwithstanding the foregoing, Aventis shall be entitled to [**]%
of any recovery of legal fees from Amgen or Kirin-Amgen under the order of the
United Kingdom Court of Appeal dated 27 March 2003.

                  (b)   Sharing of Litigation and Settlement Expenses in the
Aventis Territory. In the event that Aventis elects to respond to, defend or
prosecute any actions, challenges, infringements, misappropriations or
proceeding by a Third Party alleging infringement described in Section 8.6
brought in the Aventis Territory or alleging infringement based upon the
manufacture, production, use, distribution for sale or sale of GA-EPO in the
Aventis Territory (other than the U.S. Amgen Patent Litigation), then: (i) legal
fees and other costs and expenses associated with such response or defense,
including those incurred by TKT at Aventis' request, shall be borne [**]% by
Aventis; (ii) costs of acquiring Third Party patents or licenses and any
settlement, court award, judgment or other damages will be borne [**]% by
Aventis; and (iii) amounts recovered from Third Parties in connection with such
response or defense shall belong [**]% to Aventis.

                                      -28-
<PAGE>

                  (c)   Sharing of Litigation and Settlement Expenses in the TKT
Territory. In the event that TKT elects to respond to, defend or prosecute any
actions, challenges, infringements, misappropriations or proceeding by a Third
Party alleging infringement described in Section 8.6 brought in the TKT
Territory or alleging infringement based upon the manufacture, production, use,
distribution for sale or sale of GA-EPO in the TKT Territory (other than the
European Amgen Patent Litigation), then: (i) legal fees and other costs and
expenses associated with such response or defense, including those incurred by
Aventis at TKT's request, shall be borne [**]% by TKT; (ii) costs of acquiring
Third Party patents or licenses and any settlement, court award, judgment or
other damages will be borne [**]% by TKT; and (iii) amounts recovered from Third
Parties in connection with such response or defense shall belong [**]% to TKT.

            8.6.4 Second Right to Respond.

                  (a)   TKT's Second Right to Respond. In the event that Aventis
elects not to respond to, defend or prosecute any actions, challenges,
infringements, misappropriations or proceeding by a Third Party alleging
infringement described in Section 8.6 brought in the Aventis Territory or
alleging infringement based upon the manufacture, production, use, distribution
for sale or sale of GA-EPO in the Aventis Territory, within sixty (60) days of
becoming aware of or being notified of such actions, challenges, infringements,
misappropriations or proceedings, then TKT shall have the option to do so at
TKT's sole cost, provided that in such case all amounts so recovered from any
Third Party shall be retained by TKT and TKT shall have no further obligations
to Aventis with respect to the response or defense thereof.

                  (b)   Aventis' Second Right To Respond. In the event that TKT
elects not to respond to, defend or prosecute any actions, challenges,
infringements, misappropriations or proceeding by a Third Party alleging
infringement described in Section 8.6 brought in the TKT Territory or alleging
infringement based upon the manufacture, production, use, distribution for sale
or sale of GA-EPO in the TKT Territory within sixty (60) days of becoming aware
of or being notified of such actions, challenges, infringements,
misappropriations or proceedings, then Aventis shall have the option to do so at
Aventis' sole cost, provided that in such case all amounts so recovered from any
Third party shall be retained by Aventis and Aventis shall have no further
obligations to TKT with respect to the response or defense thereof.

      8.7   Costs of Acquiring Additional Technology other than Manufacturing
Know-How. In the event that either the R&D Oversight Committee or the
Development Committee determines that it is necessary or desirable for Aventis
to acquire any Third Party patent or license in connection with the development
or manufacture of GA-EPO covered by the TKT Patent Rights or which uses the TKT
Technology in the Aventis Territory, other than patents or licenses which are
included in Manufacturing Know-How, then the costs of acquiring such Third Party
patent or license shall be shared [**]% by Aventis and [**]% by TKT. The cost
sharing provisions described in this Section 8.7 shall only apply to Third Party
patent or license acquisitions approved unanimously by the R&D Oversight
Committee or the Development Committee.

                                      -29-
<PAGE>

                                    ARTICLE 9

                                 CONFIDENTIALITY

      9.1   Nondisclosure Obligations.

            9.1.1 General. Except as otherwise provided in this Article 9,
during the term of this Agreement and for a period of ten (10) years thereafter,
both parties shall maintain in confidence and use only for purposes specifically
authorized under this Agreement (i) confidential information and data received
from the other party resulting from or related to the development of GA-EPO and
(ii) all information and data not described in clause (i) but supplied by the
other party under this Agreement marked "Confidential."

            9.1.2 Limitations. For purposes of this Article 9, information and
data described in paragraph (i) or (ii) shall be referred to as "Information."
To the extent it is reasonably necessary or appropriate to fulfill its
obligations or exercise its rights under this Agreement, a party may disclose
Information it is otherwise obligated under this Section not to disclose to its
Affiliates, sublicensees, consultants, outside contractors and clinical
investigators, on a need-to-know basis on condition that such entities or
persons agree to keep the Information confidential for the same time periods and
to the same extent as such party is required to keep the Information
confidential; and a party or its sublicensees may disclose such Information to
government or other regulatory authorities to the extent that such disclosure is
reasonably necessary to obtain patents or authorizations to conduct clinical
trials of, and to commercially market, GA-EPO. The obligation not to disclose
Information shall not apply to any part of such Information that (i) is or
becomes part of the public domain other than by unauthorized acts of the party
obligated not to disclose such Information or its Affiliates or sublicensees;
(ii) can be shown by written documents to have been disclosed to the receiving
party or its Affiliates or sublicensees by a Third Party, provided such
Information was not obtained by such Third Party directly or indirectly from the
other party under this Agreement pursuant to a confidentiality agreement; (iii)
prior to disclosure under this Agreement, was already in the possession of the
receiving party or its Affiliates or sublicensees, provided such Information was
not obtained directly or indirectly from the other party under this Agreement
pursuant to a confidentiality agreement; (iv) can be shown by written documents
to have been independently developed by the receiving party or its Affiliates
without breach of any of the provisions of this Agreement; or (v) is disclosed
by the receiving party pursuant to oral questions, interrogatories, requests for
information or documents, subpoena, civil investigative demand issued by a court
or governmental agency; provided that the receiving party notifies the other
party immediately upon receipt thereof (and provided that the disclosing party
furnishes only that portion of the Information which it is advised by counsel is
legally required). Notwithstanding anything to the contrary herein, TKT may
disclose Information, including this Agreement, to potential TKT sublicensees
provided that such potential sublicensees are bound to a confidentiality
agreement with TKT on terms similar to the terms hereof.

                                      -30-
<PAGE>

            9.2   Materials.

                  9.2.1 Cell Line and Master Cell Bank. Neither TKT nor Aventis
shall provide to or permit access by a Third Party to the cell line used to
create the master cell bank or the master cell bank (collectively, the "Cell
Materials"), other than a manufacturer of GA-EPO pursuant to an agreement with
TKT or Aventis which requires such manufacturer to take adequate steps to
protect the confidentiality of the Cell Materials and which prohibits such
manufacturer from supplying or sending the Cell Materials to any other Third
Party. TKT and Aventis shall each take appropriate steps to prevent Third
Parties from gaining access to the Cell Materials, other than pursuant to this
subsection, with the same precautions used by TKT and Aventis for confidential
materials having a similar commercial value.

                  9.2.2 Samples. Samples of compounds synthesized, purified or
developed in the course of the Research and Development Program shall not be
supplied or sent by either party to any Third Party, other than to regulatory
agencies or for use in clinical trials, unless protected by an appropriate
materials transfer agreement. Samples of compounds other than those described
above provided by one party (the "supplying party") to the other party (the
"receiving party") in the course of the Research Program shall not be supplied
or sent by the receiving party to any Third Party, other than to regulatory
agencies or for use in clinical trials, without the written consent of the
supplying party.

      9.3   Terms of this Agreement. TKT and Aventis each agree not to disclose
any terms or conditions of this Agreement to any Third Party without the prior
consent of the other party, except as required by applicable law. If TKT
determines that it is required to file with the Securities and Exchange
Commission or other governmental agency this Agreement as an exhibit to the
registration statement relating to the IPO or otherwise, TKT shall request
confidential treatment of such portions of this Agreement as it and Aventis
shall together determine. Notwithstanding the foregoing, within 15 days after
the execution of this Agreement, Aventis and TKT shall agree upon the substance
of information that can be used as a routine reference in the usual course of
business to describe the terms of this transaction, and Aventis and TKT may
disclose such information, as modified by mutual agreement from time to time,
without the other party's consent; provided, however, that if either party
determines that excessive use of such statement is made by the other party, then
the party determined to be using such statement excessively shall, upon notice
by the other party, cease making such statement.

      9.4   Press Release. Aventis and TKT agree not to issue any press release
or public announcement concerning this Agreement or any activities contemplated
hereunder without the prior written consent of the other party. If either party
determines that it is necessary or advisable under any law, rule or regulation,
including but not limited to the rules and regulations promulgated by the United
States Securities and Exchange Commission, to file a public statement regarding
this Agreement or any activities contemplated hereby, the consent of the other
party shall not be required for such statement; provided, however, that such
public statement shall first be provided to

                                      -31-
<PAGE>

such other party, and such other party shall have a reasonable opportunity to
comment on such public statement.

      9.5   Publications.

            9.5.1 Procedure. Each party recognizes the mutual interest in
obtaining valid patent protection. Consequently, either party and its employees
or consultants or any other Third Party wishing to make a publication (including
any oral disclosure made without obligation or confidentiality) relating to work
performed by such party as part of the Program (the "Publishing Party") shall
transmit to the other party (the "Reviewing Party") a copy of the proposed
written publication at least forty-five (45) days prior to submission for
publication, or an abstract of such oral disclosure at least fifteen (15) days
prior to submission of the abstract or the oral disclosure, whichever is
earlier. The Reviewing Party shall have the right (a) to propose modifications
to the publication for patent reasons, (b) to request a delay in publication or
presentation in order to protect patentable information, or (c) to request that
the information be maintained as a trade secret and, in such case, the
Publishing Party shall not make such publication.

            9.5.2 Delay. If the Reviewing Party requests a delay as described in
subsection 9.5.1(b) the Publishing Party shall delay submission or presentation
of the publication for a period of ninety (90) days to enable patent
applications protecting each party's rights in such information to be filed.

            9.5.3 Resolution. Upon the receipt of written approval of the
Reviewing Party the Publishing Party may proceed with the written publication or
the oral presentation.

            9.5.4 Injunctive Relief. The parties hereto understand and agree
that remedies at law may be inadequate to protect against any breach of any of
the provisions of this Article 9 by either party or their employees, agents,
officers or directors or any other person acting in concert with it or on its
behalf. Accordingly, each party shall be entitled to the granting of injunctive
relief by a court of competent jurisdiction against any action that constitutes
any such breach of this Article 9. It is understood that such injunctive relief
is intended solely as provisional relief pending the dispute resolution
procedures described in Section 13.6 hereof.

                                   ARTICLE 10

                         REPRESENTATIONS AND WARRANTIES

      10.1  General.

            10.1.1 Authorization. Each party represents and warrants to the
other that it has the legal right and power to enter into this Agreement, to
extend the rights and licenses granted to the other in this Agreement, and to
fully perform its obligations hereunder, and that the performance of such
obligations will not conflict with its charter documents or any agreements,
contracts or other arrangements to which it is a party.

                                      -32-
<PAGE>

            10.1.2 No Inconsistent TKT Arrangements. TKT represents and warrants
that it has full power and authority to grant the license set forth in Article 3
hereof and that there are no agreements, assignments, encumbrances or other
arrangements inconsistent with this Agreement including, without limitation, any
obligations to governmental agencies, private foundations or corporate entities
resulting from acceptance of research grant monies, equity investments,
corporate sponsorships or otherwise.

            10.1.3 Exclusivity. TKT represents and warrants that Aventis is the
exclusive licensee of the TKT Technology owned by TKT and the TKT Patent Rights
with respect to the manufacture, use or sale of GA-EPO in the Aventis Territory.

            10.1.4 Licensed Technology.

                   (a)  TKT represents and warrants that, as of the Effective
Date, the TKT Patent Rights and TKT Technology do not include any intellectual
property licensed to TKT from a Third Party other than those included in a
License Agreement dated May 1997 between TKT and the University of Iowa Research
Foundation.

                   (b)  Aventis represent and warrants that, as of the Amendment
Effective Date, it has the right to license to TKT the Aventis Technology and
[**].

      10.2  Patent Validity.

            10.2.1 Title.

                  (a)   TKT represents and warrants that as of the Effective
Date, it possesses the exclusive right, title and interest in and to the TKT
Technology owned by TKT and the TKT Patent Rights and that it has the full legal
right and power to: (i) enter into the obligations set forth in this Agreement;
and (ii) grant the rights and licenses set forth in Article 3.

                  (b)   Aventis represents and warrants that as of the Amendment
Effective Date, it possesses the exclusive right, title and interest in and to
the Aventis Technology owned by Aventis and that it has the full legal right and
power to: (i) enter into the obligations set forth in this Agreement; and (ii)
grant the rights and licenses set forth in Article 3.

            10.2.2 No Encumbrances. TKT represents and warrants as of the
Effective Date, to the best of its actual knowledge and based upon the advice of
its counsel, to the best of such counsel's actual knowledge without undertaking
any independent investigation, (i) that there were no encumbrances, liens or
other claims affecting the TKT Technology owned by TKT or the TKT Patent Rights
and (ii) that such TKT Technology and TKT Patent Rights were valid, enforceable
and free from infringement, and that there were no pending or threatened
actions, suits or proceedings relating thereto or to GA-EPO.

                                      -33-
<PAGE>

            10.2.3 Non-Infringement. TKT represents and warrants that as of the
Effective Date, to the best of its actual knowledge and based upon the advice of
its counsel, to the best of such counsel's actual knowledge without undertaking
any independent investigation, there were no legal obstacles, including no
patent rights or other proprietary rights of others, which will prevent it from
carrying out its obligations under this Agreement or prevent Aventis from
carrying out its obligations under this Agreement or which will be infringed by
the performance of either party's obligations under this Agreement.

                                   ARTICLE 11

                                    INDEMNITY

      11.1  Aventis Indemnity Obligations. In the absence of TKT's negligence or
breach of representation, warranty, covenant or agreement by TKT, Aventis agrees
to defend, indemnify and hold TKT, its Affiliates and their respective employees
and agents harmless from all claims, losses, damages or expenses arising as a
result of (a) actual or asserted violations of any applicable law or regulation
by Aventis or its Affiliates or sublicensees (acting under an agreement with
Aventis) by virtue of which GA-EPO covered by the TKT Patent Rights or which
uses the TKT Technology manufactured, distributed or sold shall be alleged or
determined to be adulterated, misbranded, mislabeled or otherwise not in
compliance with any applicable law or regulation or (b) claims for bodily
injury, death or property damage attributable to Aventis's performance of its
obligations under this Agreement or the manufacture, distribution, sale or use
of GA-EPO covered by the TKT Patent Rights or which uses the TKT Technology by
Aventis or its Affiliates or sublicensees (acting under an agreement with
Aventis).

      11.2  TKT Indemnity Obligations. In the absence of Aventis's negligence or
a breach of representation, warranty, covenant or agreement by Aventis, TKT
agrees to defend, indemnify and hold Aventis, its Affiliates and sublicensees
and their respective employees and agents harmless from all claims, losses,
damages and expenses arising as a result of (a) actual or asserted violations of
any applicable law or regulation by TKT or its Affiliates or licensees (acting
under an agreement with TKT) by virtue of which GA-EPO covered by the TKT Patent
Rights or which uses the TKT Technology manufactured, distributed or sold shall
be alleged or determined to be adulterated, misbranded, mislabeled or otherwise
not in compliance with any applicable law or regulation or (b) claims for bodily
injury, death or property damage attributable to TKT's performance of its
obligations under this Agreement, or the manufacture, distribution, sale or use
of GA-EPO covered by the TKT Patent Rights or which uses the TKT Technology by
TKT or its Affiliates or licensees (acting under an agreement with TKT).

      11.3  Procedure. A party or any of its Affiliates or their respective
employees or agents (the "Indemnitee") that intends to claim indemnification
under this Article 11 shall promptly notify the other party (the "Indemnitor")
of any claim, loss, damage, or expenses in respect of which the Indemnitee
intends to claim such indemnification

                                      -34-
<PAGE>

reasonably promptly after the Indemnitee is aware thereof, and the Indemnitor
shall assume the defense of any related third party action, suit or proceeding
with counsel mutually satisfactory to the parties; provided, however, that an
Indemnitee shall have the right to retain its own counsel, with the fees and
expenses to be paid by the Indemnitor, if representation of such Indemnitee by
the counsel retained by the Indemnitor would be inappropriate due to actual or
potential differing interests between such Indemnitee and any other party
represented by such counsel in such proceedings. The indemnity agreement in this
Article 11 shall not apply to amounts paid in settlement of any claim, loss,
damage or expense if such settlement is effected without the consent of the
Indemnitor, which consent shall not be withheld unreasonably. The failure of an
Indemnitee to deliver notice to the Indemnitor within a reasonable time after
becoming aware of any such matter, if prejudicial to the Indemnitor's ability to
defend such action, shall relieve the Indemnitor of any liability to the
Indemnitee under this Article 11. The Indemnitor shall not have any liability to
any Indemnitee otherwise than under this Article 11. The Indemnitee under this
Article 11 and its employees and agents shall cooperate fully with the
Indemnitor and its legal representatives in the investigation of any matter
covered by this indemnification. The Indemnitor shall additionally be liable to
pay the reasonable legal costs and attorneys' fees incurred by the Indemnitee in
establishing a successful claim for indemnity hereunder.

      11.4  Insurance. For the period starting with the First Commercial Sale of
GA-EPO, Aventis and TKT shall each maintain product liability insurance with
respect to development, manufacture and sale of GA-EPO covered by the TKT Patent
Rights or which uses the TKT Technology in reasonable amounts determined after
consultation with each other, for the term of this Agreement (if such insurance
is an occurrence-basis policy) or for an additional ten years after the
expiration or termination of this Agreement (if such insurance is a claims-made
basis policy).

                                   ARTICLE 12

                              TERM AND TERMINATION

      12.1  Expiration. Unless terminated earlier in accordance with Section
12.4, this Agreement shall expire upon the later to occur of (i) the expiration
of the royalty obligations of Aventis under Section 12.2, and (ii) the
expiration of the royalty obligations of TKT under Section 12.3.

      12.2  Expiration of Royalty Obligations of Aventis. Unless terminated
earlier pursuant to Section 12.4, the obligation of Aventis to pay royalties in
accordance with Section 7.2 shall terminate and the licenses granted by TKT to
Aventis hereunder shall become fully paid and perpetual, with respect to each
country in the Aventis Territory, upon the later of (i) ten years after the
First Commercial Sale of GA-EPO covered by the TKT Patent Rights or which uses
the TKT Technology by Aventis or its Affiliates or sublicensees in such country
and (ii) the last to expire of any of the then existing patents included in the
TKT Patent Rights in such country.

                                      -35-
<PAGE>

      12.3  Expiration of Royalty Obligations of TKT. Unless terminated earlier
pursuant to Section 12.4, the obligation of TKT to pay royalties in accordance
with (i) Section 7.2 shall terminate and the licenses granted by Aventis to TKT
under Section 3.2 shall become fully paid and perpetual, with respect to each
country in the TKT Territory, upon the later of (a) ten years after the First
Commercial Sale of [**] GA-EPO covered by the TKT Patent Rights or which uses
the TKT Technology or Aventis Technology by TKT or its Affiliates or
sublicensees in such country and (b) the last to expire of any of the then
existing patents included in the TKT Patent Rights in such country, and (ii)
Section 7.3 shall terminate and the licenses granted by Aventis to TKT under
Section 3.4 shall become fully paid and perpetual, with respect to each country
in the TKT Territory, upon the later of (a) ten years after the First Commercial
Sale of by TKT or its Affiliates or sublicensees in such country and (b) the
last to expire of any of the then existing patents covering [**] in such
country.

      12.4  Termination. This Agreement may be terminated in the following
circumstances:

            12.4.1 By the non-breaching party by reason of a material breach not
described in subsection 12.4.5 that the breaching party fails to remedy within
90 days after written notice thereof by the non-breaching party;

            12.4.2 By Aventis at any time for any reason prior to the date of an
Aventis Positive Notification;

            12.4.3 By Aventis upon 180 days prior written notice with respect to
all or a portion of the Aventis Territory, if, in its reasonable judgment,
Aventis determines that toxicities or side effects directly attributable to
GA-EPO covered by the TKT Patent Rights or which uses the TKT Technology have
rendered it such a safety risk to the patient population that GA-EPO covered by
the TKT Patent Rights or which uses the TKT Technology is commercially
nonviable;

            12.4.4 By Aventis, upon 180 days prior written notice, with respect
to any portion of the Aventis Territory if, after consultation with TKT, Aventis
determines that GA-EPO covered by the TKT Patent Rights or which uses the TKT
Technology is commercially nonviable;

            12.4.5 [**] at any time following [**] with respect to the relevant
portion of the Aventis Territory, in the event that [**] and Aventis fails to
remedy or take reasonable action to initiate a remedy of such default within
ninety (90) days after notice thereof by TKT; provided that termination by TKT
pursuant to this subsection 12.4.5 shall be TKT's sole remedy [**].

            12.4.6 If a competing GA-EPO product is introduced into any country
in the Aventis Territory, and TKT does not have issued patents or pending claims
under the patents included in the TKT Patent Rights which (if issued, in the
case of pending claims) will enable a patent infringement action to be
initiated, then Aventis has the right to terminate as to any such country on 180
days notice; or

                                      -36-
<PAGE>

            12.4.7 By either party upon bankruptcy, insolvency, dissolution or
winding up of the other.

      12.5  Effect of Termination. Expiration of termination of this Agreement
shall not relieve the parties of any obligation accruing prior to such
expiration or termination. The provisions of Article 7, Article 8, Article 9 and
Article 11 shall survive the expiration or termination of this Agreement;
provided, however that (i) the royalty obligations of the parties set forth in
Article 7 shall not survive expiration of this Agreement, and (ii) the licenses
granted hereunder shall survive expiration of this Agreement in accordance with
the terms of Sections 12.2 and 12.3. In the event of a termination of this
Agreement pursuant to subsections 12.4.1 to 12.4.7, then all TKT Patent Rights
licensed hereunder with respect to the portion of the Aventis Territory
terminated will be returned to TKT and, except in the event that this Agreement
is terminated by TKT pursuant to subsection 12.4.1, copies of all regulatory
filings and related supporting and other materials prepared in connection with
such terminated portion of the Aventis Territory shall also be delivered to and
available for use by TKT, and in any event Aventis will immediately cease to
sell GA-EPO covered by the TKT Patent Rights or which uses the TKT Technology in
the relevant portion of the Aventis Territory with respect to which this
Agreement is terminated. In the event of termination of this Agreement in all
countries within the Aventis Territory, Aventis will return to TKT the cell line
used to create the master cell bank, the master cell bank and any cells produced
from the use of such master cell bank which are in Aventis's possession, or, if
instructed by TKT, Aventis shall destroy such materials and provide written
confirmation to TKT of their destruction. Except in the event that this
Agreement is terminated by TKT pursuant to subsection 12.4.1, Aventis shall, to
the extent legally permissible, take all additional action reasonably necessary
to assign all of its right, title and interest in and transfer possession and
control to TKT of the regulatory filings prepared by Aventis to the extent that
such filings relate to GA-EPO covered by the TKT Patent Rights or which use the
TKT Technology and any regulatory approvals received by Aventis to the extent
that such approvals relate to GA-EPO covered by the TKT Patent Rights or which
use the TKT Technology; provided, however, that Aventis may retain a joint
ownership interest in such filings and approvals to the extent that such filings
or approvals are necessary under this Agreement for portions of the Aventis
Territory with respect to which this Agreement has not been terminated or for
the development or commercialization by Aventis of products other than GA-EPO
covered by the TKT Patent Rights or which use the TKT Technology. Except in the
event that this Agreement is terminated by Aventis pursuant to Section 12.4.1,
the licenses granted to TKT hereunder shall survive any termination of this
Agreement. The licenses granted to TKT hereunder shall immediately terminate in
the event that this Agreement is terminated by Aventis under Section 12.4.1.

                                   ARTICLE 13

                            RELEASES AND DELIVERABLES

      13.1  Release by Aventis. Aventis hereby (i) releases and discharges TKT
from its obligations under Section 8.6.3 of this Agreement with respect to time
periods prior to the Amendment Effective Date to pay [**] percent ([**]%) of the
legal fees and other

                                      -37-
<PAGE>

costs and expenses associated with the U.S. Amgen Patent Litigation and the
European Amgen Patent Litigation and (ii) releases and forever discharges TKT
from any liability associated with any failure of TKT to comply with or
otherwise perform any obligations imposed on TKT pursuant to the terms and
conditions of this Agreement as in effect immediately prior to the Amendment
Effective Date. Nothing contained in the previous sentence is intended to waive
any rights of Aventis or release TKT from any liabilities or other obligations
that may arise after the Amendment Effective Date. For purposes of clarity, it
is understood that all legal fees and other costs and expenses, as well as all
recoveries from Third Parties, associated with the Amgen Patent Litigation
relating to periods after the Amendment Effective Date, shall be allocated
between the parties as set forth in Subsection 8.6.3 as in effect immediately
prior to the Amendment Effective Date.

      13.2  Release by TKT. TKT hereby (i) acknowledges and agrees that Aventis
has fully satisfied all of its obligations under the terms and conditions of
this Agreement as in effect immediately prior to the Amendment Effective Date,
including, but not limited to, all obligations imposed on Aventis pursuant to
Sections 5.1.2 and 5.8.1 as in effect prior to the Amendment Effective Date, and
(ii) releases and forever discharges Aventis from any liability associated with
any failure of Aventis to comply with or otherwise perform any obligations
imposed on Aventis pursuant to the terms and conditions of this Agreement as in
effect immediately prior to the Amendment Effective Date. Nothing contained in
the previous sentence is intended to waive any rights of TKT or release Aventis
from any liabilities or other obligations that may arise after the Amendment
Effective Date. [**]. Nothing contained herein shall limit any rights TKT may
have [**].

      13.3  [**] Regulatory Filings and Regulatory Approvals.

            13.3.1 Regulatory Filings. Aventis hereby agrees to [**]. Except to
the extent that other deadlines are agreed to elsewhere in this Agreement,
promptly, but not later than one hundred eighty (180) days after the Amendment
Effective Date, TKT and Aventis shall [**]. Aventis shall either, at Aventis'
option, (i) [**] or (ii) [**].

            13.3.2 Regulatory Information. Promptly, but in no event later than
ninety (90) days after the Amendment Effective Date, Aventis shall deliver to
TKT copies of all files of Aventis and its Affiliates not previously delivered
to TKT pertaining to the Regulatory Filings and the Regulatory Approvals and all
related correspondence to or from Regulatory Authorities related to such
Regulatory Filings or Regulatory Approvals and all documents referred to in the
regulatory chronology for each Regulatory Filing or Regulatory Approval, in each
case to the extent such information is within the possession of Aventis and its
Affiliates.

                                   ARTICLE 14

                                  MISCELLANEOUS

      14.1  Force Majeure. Neither party shall be held liable or responsible to
the other party nor be deemed to have defaulted under or breached this Agreement
for failure

                                      -38-
<PAGE>

or delay in fulfilling or performing any term of this Agreement when such
failure or delay is caused by or results from causes beyond the reasonable
control of the affected party, including but not limited to fire, floods,
embargoes, war, acts of war (whether war is declared or not), locusts,
insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances, acts of God or acts, omissions or delays in acting by any
governmental authority or the other party.

      14.2  Assignment. This Agreement may not be assigned or otherwise
transferred by either party without the consent of the other party; provided,
however, that either TKT or Aventis may, without such consent, assign its rights
and obligations under this Agreement (i) in connection with a corporate
reorganization, to any Affiliate, all or substantially all of the equity
interest of which is owned and controlled by such party or its direct or
indirect parent corporation, or (ii) in connection with a merger, consolidation
or sale of substantially all of such party's assets to an unrelated third party;
provided, however, that such party's rights and obligations under this Agreement
shall be assumed by its successor in interest in any such transaction and shall
not be transferred separate from all or substantially all of its other business
assets, including those business assets that are the subject of this Agreement.
Any purported assignment in violation of the preceding sentence shall be void.
Any permitted assignee shall assume all obligations of its assignor under this
Agreement.

      14.3  Severability. Each party hereby agrees that it does not intend to
violate any public policy, statutory or common laws, rules, regulations, treaty
or decision of any government agency or executive body thereof of any country or
community or association of countries. Should one or more provisions of this
Agreement be or become invalid, the parties hereto shall substitute, by mutual
consent, valid provisions for such invalid provisions which valid provisions in
their economic effect are sufficiently similar to the invalid provisions that it
can be reasonably assumed that the parties would have entered into this
Agreement with such valid provisions. In case such valid provisions cannot be
agreed upon, the invalidity of one or several provisions of this Agreement shall
not affect the validity of this Agreement as a whole, unless the invalid
provisions are of such essential importance to this Agreement that it is to be
reasonably assumed that the parties would not have entered into this Agreement
without the invalid provisions.

      14.4  Notices. Any consent, notice or report required or permitted to be
given or made under this Agreement by one of the parties hereto to the other
shall be in writing, delivered personally or by facsimile (and promptly
confirmed by telephone, personal delivery or courier) or courier, postage
prepaid (where applicable), addressed to such other party at its address
indicated below, or to such other address as the addressee shall have last
furnished in writing to the addressor and shall be effective upon receipt by the
addressee.

If to TKT:              Transkaryotic Therapies, Inc.
                        700 Main Street
                        Cambridge, MA 02139
                        Attention: Chief Executive Officer

                                      -39-
<PAGE>

                        Telephone: (617) 349-0200
                        Telecopy: (617) 613-4004

with a copy to:         Transkaryotic Therapies, Inc.
                        700 Main Street
                        Cambridge, MA 02139
                        Attention: Legal Department
                        Telephone: (617) 349-0200
                        Telecopy: (617) 349-0550

If to Aventis:          Aventis Pharmaceuticals Inc.
                        200 Crossing Boulevard
                        BX2-700A
                        Bridgewater, NJ 08809
                        Attention: Vice President, Legal Corporate Development
                        Telephone: (908) 231-3537
                        Telecopy: (908) 231-4480

with a copy to:         Morgan, Lewis & Bockius LLP
                        502 Carnegie Center
                        Princeton, NJ 08540
                        Attention: Randall B. Sunberg, Esq.
                        Telephone: (609) 919-6600
                        Telecopy: (609) 919-6639

      14.5  Applicable Law. This Agreement shall be governed by and construed in
accordance with the laws of the State of Delaware, without giving effect to the
choice of law provisions thereof.

      14.6  Dispute Resolution. Any disputes arising between the parties
relating to, arising out of or in any way connected with this Agreement or any
term or condition hereof, or the performance by either party of its obligations
hereunder, whether before or after termination of this Agreement, shall be
promptly presented to the Chief Executive Officers of TKT and Aventis for
resolution and if the Chief Executive Officers or their designees cannot
promptly resolve such disputes, then such dispute shall be finally resolved by
binding arbitration, except that disputes arising within the Development
Committee shall be ultimately resolved, without the use of arbitration, by the
Chief Executive Officer of Aventis. Whenever a party shall decide to institute
arbitration proceedings, it shall give written notice to that effect to the
other party. The party giving such notice shall refrain from instituting the
arbitration proceedings for a period of sixty (60) days following such notice.
Any arbitration hereunder shall be conducted under the commercial rules of the
American Arbitration Association. Each such arbitration shall be conducted in
the English language by a panel of three arbitrators appointed in accordance
with such rules; provided, however, that both parties hereto shall be entitled
to representation by counsel, to appear and present written and oral evidence
and argument and to cross-examine witnesses presented by the other party. The
arbitral panel (i) shall

                                      -40-
<PAGE>

have the authority to grant specific performance, (ii) may allocate between the
parties the costs of arbitration in such equitable manner as they may determine,
but (iii) shall not render an arbitral award contrary to the provisions of this
Agreement. The arbitral award shall be in writing and the arbitral panel shall
provide written reasons for its award. The award of the arbitral panel shall be
final and binding upon the parties hereto. Any such arbitration shall be held in
Chicago, Illinois, or any other mutually agreed location. Judgment upon the
award so rendered may be entered in any court having jurisdiction or application
may be made to such court for judicial acceptance of any award and an order of
enforcement, as the case may be. Notwithstanding the provisions of this Section
13.7, in the event of a material breach of this Agreement by TKT that TKT fails
to remedy within 90 days after written notice thereof by Aventis, Aventis shall
have the right to bring an action for specific performance by TKT or its
Affiliates of TKT's obligations hereunder, to seek an injunction with respect to
any action by TKT or its Affiliates inconsistent with any of TKT's obligations
hereunder or to bring an action against TKT or its Affiliates at law or in
equity in any court or other tribunal in which such action may properly be
brought.

      14.7  Entire Agreement. This Agreement, together with the Class D Stock
Purchase Agreement, contains the entire understanding of the parties with
respect to the subject matter hereof and supersedes the Letter Agreement dated
March 18, 1994 between TKT and Aventis and the Original License Agreement. All
express or implied agreements and understandings, either oral or written,
heretofore made are expressly merged in and made a part of this Agreement. This
Agreement may be amended, or any term hereof modified, only by a written
instrument duly executed by both parties hereto.

      14.8  Headings. The captions to the several Articles and Sections hereof
are not a part of this Agreement, but are merely guides or labels to assist in
locating and reading the several Articles and Sections hereof.

      14.9  Independent Contractors. It is expressly agreed that TKT and Aventis
shall be independent contractors and that the relationship between the two
parties shall not constitute a partnership, joint venture or agency. Neither TKT
nor Aventis shall have the authority to make any statements, representations or
commitments of any kind, or to take any action, which shall be binding on the
other, without the prior consent of the other party to do so.

      14.10 Agreement Not to Solicit Employees. During the term of this
Agreement and for a period of two (2) years following the termination of this
Agreement, TKT and Aventis agree not to seek to persuade or induce any employee
of the other company to discontinue his or her employment with that company in
order to become employed by or associated with any business, enterprise or
effort that is associated with its own business.

      14.11 Exports. The parties acknowledge that the export of technical data,
materials or products is subject to the exporting party receiving any necessary
export licenses and that the parties cannot be responsible for any delays
attributable to export controls which are beyond the reasonable control of ether
party. TKT and Aventis agree not to export or re-export, directly or indirectly,
any information, technical data, the

                                      -41-
<PAGE>

direct product of such data, samples or equipment received or generated under
this Agreement in violation of any governmental regulations which may be
applicable, including, but not limited to, the Export Administration Act of
1979, as amended, its rules and regulations, including, but not limited to Part
779 of the United States Export Control Regulations, published by the United
States Department of Commerce, and other applicable export control laws. TKT and
Aventis agree to obtain similar covenants from their licensees, sublicensees and
contractors with respect to the subject matter of this Section 13.12.

      14.12 Waiver. The waiver by either party hereto of any right hereunder or
the failure to perform or of a breach by the other party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other party whether of a similar nature or otherwise.

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

                            [SIGNATURE PAGE FOLLOWS]

                                      -42-
<PAGE>

      IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first set forth above.

                                        AVENTIS PHARMACEUTICALS INC.

                                        By:       /s/Richard J. Markham
                                           --------------------------------
                                           Name:  Richard J. Markham
                                           Title: Chief Operating Officer

                                        TRANSKARYOTIC THERAPIES, INC.

                                            By: /s/ Michael J. Astrue
                                               ----------------------------
                                               Name: Michael J. Astrue
                                               Title: President and Chief
                                                      Executive Officer

                                      -43-
<PAGE>

                                  SCHEDULE 1.3
                              NO SUBLICENSE RIGHTS

1.  [**]

2.  [**]

                                      -44-

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00066-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00066-of-00352.parquet"}]]