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-

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            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

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