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Sample Business Contracts

License Agreement - Children's Medical Center Corp. and EntreMed Inc.

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                              LICENSE AGREEMENT

         This Agreement is made and entered into this _____ day December, 1996
(the Effective Date), by and between CHILDREN'S MEDICAL CENTER CORPORATION, a
corporation duly organized and existing under the laws of the Commonwealth of
Massachusetts and having its principal office at 300 Longwood Avenue, Boston,
Massachusetts, 02115, U.S.A. (hereinafter referred to as CMCC), and ENTREMED,
INC., a corporation duly organized under the laws of Maryland and having its
principal office at 9610 Medical Center Drive, Suite 200, Rockville, MD 20850
(hereinafter referred to as LICENSEE).

                                   WITNESSETH

         WHEREAS, CMCC is the owner of certain "Patent Rights" (as later
defined herein) relating to CMCC Case No. 474, "Endostatin, An Inhibitor of
Angiogenesis" (US. Patent Applications listed in Exhibit A attached hereto) and
has the right to grant licenses under said Patent Rights;

         WHEREAS, CMCC desires to have the Patent Rights utilized in the public
interest and is willing to grant a license thereunder;

         WHEREAS, LICENSEE has represented to CMCC, to induce CMCC to enter
into this Agreement, that LICENSEE is capable of the development, production,
manufacture, marketing and sale of products similar to the "Licensed
Product(s)" (as later defined herein) and/or the use of the "Licensed
Process(es)" (as later defined herein) and that it shall commit itself to a
thorough, vigorous and diligent program of exploiting the Patent Rights so that
public utilization shall result therefrom; and

         WHEREAS, LICENSEE desires to obtain a license under the Patent Rights
upon the terms and conditions hereinafter set forth.

         NOW, THEREFORE, in consideration of the premises and the mutual
covenants herein, the parties hereto agree as follows:





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                            ARTICLE I - DEFINITIONS

         For the purpose of this Agreement, the following words and phrases
shall have the following meanings:

1.1      "LICENSEE" shall mean EntreMed, Inc. and any Subsidiary or joint
         venture of EntreMed, Inc.

1.2      "Sublicensee" shall mean any corporation, partnership or business
         organization which is not controlled directly or indirectly by
         LICENSEE but to whom LICENSEE transfers know-how, rights or products
         to enable said party to sell Licensed Products and/or Licensed
         Processes.

1.3      "Subsidiary" shall mean any corporation, company or other entity more
         than fifty percent (50%) of whose voting stock is owned or controlled
         directly or indirectly by LICENSEE

1.4      "Patent Rights" shall mean all of the following CMCC intellectual
         property:

         1.4.1.  The United States and foreign patents and/or patent
                 applications listed in AppendixEA;

         1.4.2.  United States and foreign patents issued from the applications
                 listed in Appendix A and from divisionals and continuations of
                 these applications;

         1.4.3.  Claims of U.S. and foreign continuation-in-part applications,
                 and of the resulting patents, which are directed to subject
                 matter specifically described in the U.S. and foreign
                 applications listed in Appendix A;

         1.4.4.  Claims of all later filed foreign patent applications, and of
                 the resulting patents, which are directed to subject matter
                 specifically described in the United States patent and/or
                 patent applications described in (a), (b), or (c) above;

         1.4.5.  Any reissues of United States patents described in (a), (b),
                 (c), or (d) above.





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1.5      A "Licensed Product" shall mean any product or part thereof which:

         1.5.1.  Is covered in whole or in part by an issued, unexpired claim
                 or a pending claim contained in the Patent Rights in the
                 country in which any Licensed Product is made, used, or sold;

         1.5.2.  Is manufactured by using a process which is covered in whole
                 or in part by an issued, unexpired claim or a pending claim
                 contained in the Patent Rights in the country in which any
                 Licensed Process is used or in which the Licensed Product is
                 used or sold.

1.6      A "Licensed Process" shall mean any process which is  covered in whole
         or in part by an issued, unexpired claim or a pending claim contained
         in the Patent Rights.

1.7      "Net Sales" shall mean the gross amount invoiced for all sales of
         Licensed Products by LICENSEE, its Subsidiaries or its Sublicensees
         less:

         1.7.1.  trade, quantity and cash discounts, allowed, incurred or
                 actually taken;

         1.7.2.  sales taxes directly related to the sale to the extent
                 included in the gross invoice price;

         1.7.3.  the portion of freight, postage and shipping insurance
                 expenses paid by LICENSEE;

         1.7.4.  value added tax, sales or turnover tax, or excise taxes or
                 duties which are included in said invoiced amount;

         1.7.5.  rebates accrued, incurred or paid to Federal Medicaid or State
                 Medicare and amounts exactly repaid or credited by reason of
                 rejections or the return of Licensed Products (due to recalls,
                 dating or other reasons) and retroactive deductions; and

         1.7.6.  cost of export licenses and any taxes, fees or other charges
                 associated with the exportation or importation of Licensed
                 Products.





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         1.7.7   No deductions shall be made for commissions paid to
                 individuals employed by LICENSEE and on its payroll, or for
                 the cost of collections.

         1.7.8   Licensed Products shall be considered "sold" when billed out or
                 invoiced.

                         ARTICLE II - GRANT OF LICENSE

2.1      CMCC hereby grants to LICENSEE the exclusive worldwide right and
         license to make, have made, use, lease and sell the Licensed Products,
         and to practice the Licensed Processes to the end of the term for
         which the Patent Rights are granted unless sooner terminated according
         to the terms hereof. CMCC shall retain a royalty-free, nonexclusive,
         irrevocable license to practice the Patent Rights for research
         purposes only.

2.2      LICENSEE agrees that it will use its best efforts to manufacture
         substantially in the United States the Licensed Products leased or
         sold in the United States.

2.3      To establish exclusivity for LICENSEE, CMCC hereby agrees that it
         shall not grant any other license to  make, have made, use, lease
         and/or sell Licensed Products or to utilize Licensed Processes during
         the period of time in which this Agreement is in effect.

2.4      LICENSEE shall have the right to enter into sublicensing agreements
         for the rights, privileges, and licenses granted hereunder. Such
         sublicenses will expire upon the expiration of LICENSEE's rights
         granted herein.





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2.5      LICENSEE agrees that any sublicense granted by it shall provide that
         the obligations to CMCC of Articles II, V, VII, VIII, IX, X, XII,
         XIII, and XV of this Agreement shall be binding upon the sublicensee
         as if it were a party to this Agreement.  LICENSEE further agrees to
         attach copies of these Articles to sublicense agreements.  Further,
         LICENSEE hereby agrees that every sublicensing agreement to which it
         shall be a party and which shall relate to the rights, privileges and
         license granted hereunder shall contain a statement setting forth the
         event or date upon which LICENSEE'S exclusive rights, privileges and
         license hereunder shall terminate.

2.6      LICENSEE agrees to forward to CMCC a copy of any and all fully
         executed sublicense agreements, and further agrees to forward to CMCC
         annually a copy of such reports received by LICENSEE from its
         sublicensees during the preceding twelve (12) month period under the
         sublicenses as shall be pertinent to a royalty accounting under said
         sublicense agreements.

2.7      LICENSEE shall not receive from sublicensees anything of value in lieu
         of cash payments based upon payment obligations of any sublicense
         under this Agreement, without the express prior written permission of
         CMCC.

2.8      The license granted hereunder shall not be construed to confer any
         rights upon LICENSEE by implication, estoppel or otherwise as to any
         technology not specifically set forth in Appendix A hereof.

2.9      LICENSEE agrees, to the best of its ability, to adhere to Public Laws
         96-517 and 98-620.


                          ARTICLE III - DUE DILIGENCE


3.1      LICENSEE shall use its best efforts to bring one or more Licensed
         Products or Licensed Processes to market through a thorough, vigorous
         and diligent program for exploitation of the Patent Rights.
         Thereafter, LICENSEE agrees that until expiration or  termination of
         this Agreement, LICENSEE shall continue active and diligent efforts to
         keep Licensed Products and/or Licensed Processes reasonably available
         to the public. CMCC agrees that LICENSEE





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         shall have complete control of all regulatory submissions of Licensed
         Products to the appropriate regulatory agencies worldwide. In the
         event LICENSEE decides not to exploit a licensed Patent Right, it
         shall promptly inform CMCC in writing and shall surrender to CMCC its
         license to that Patent Right. Only one payment will be made for each
         of the milestones recited under 3.1.1,  3.1.2,  3.1.3 and 3.1.4.   Due
         diligence shall be demonstrated by attaining the following milestones:

         3.1.1   -within 5 years of the Effective Date, the filing of an IND in
                 the U.S. for a Licensed Product by LICENSEE;

         3.1.2   -within 6.5 years of the Effective Date, the initiation of
                 Phase II trials of a Licensed Product;

         3.1.3   -within 8.5  years of the Effective Date, the initiation of
                 Phase III trials of a Licensed Product; and

         3.1.4   -within 11 years of the Effective Date, the submission of an
                 NDA or similar application to gain regulatory approval for the
                 marketing of a Licensed Product; and by continuing sponsorship
                 of related preclinical studies at Children's Hospital, if
                 appropriate.

3.2      LICENSEE acknowledges that, prior to attaining the first milestone of
         3.1.1 above, additional activities must be undertaken including but
         not limited to:  1) development of a plan describing the scientific
         and technical goals to be accomplished prior to attaining the
         milestone of 3.1.1 and allocation the LICENSEE resources, either
         internal or contracted, that will be applied in accomplishing those
         goals, 2) confirmation of the antitumor activity of one or more
         Licensed Products in one or more animal models, 3) development of
         processes for manufacturing one or more Licensed Products on a scale
         capable of producing sufficient material for testing and evaluation,
         4) conduct of preclinical toxicology and pharmacology studies, and 4)
         determination of whether Licensee or a sublicense will be initiating
         clinical trials.  Licensee agrees to keep CMCC reasonable informed of
         the additional activities by preparing at least annually a





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         written summary of the  activities planned and completed and by
         holding on at least annually a meeting with CMCC representatives to
         review progress to date.

3.3      LICENSEE acknowledges that the primary objective of CMCC in entering
         this License Agreement is to promote the development and marketing of
         Licensed Products and Processes for the public good. To this end, CMCC
         shall have the right to terminate this Agreement pursuant to Paragraph
         13.3 below if LICENSEE fails to attain any of the above milestones for
         more than six (6) months after the milestone time period because of
         business circustances such as merger, acquisition or the like.
         However, if LICENSEE can demonstrate to the satisfaction of CMCC, at
         CMCC's sole discretion, that circumstances beyond LICENSEE's control
         precluded LICENSEE from fulfilling its diligence obligations, and that
         it is unlikely that any third party could overcome these circumstances
         better than LICENSEE, then CMCC shall not exercise its termination
         rights under this Article for one year from the date on which CMCC
         give notice of termination and if LICENSEE reestablishes diligence
         towards it objectives during this one year period, any prior lack of
         diligence will be deemed cured.

                      ARTICLE IV - PAYMENTS AND ROYALTIES

4.1      For the rights, privileges and license granted hereunder, LICENSEE
         shall pay to CMCC in the manner hereinafter provided to the end of the
         term of the Patent Rights or until this Agreement shall be terminated
         as hereinafter provided, whether the milestones are achieved under the
         sponsorship of LICENSEE or a sublicensee, the following milestone
         payments totaling $1,000,000 (one million dollars):

         4.1.1   -$50,000 (fifty thousand dollars) due four (4) months from the
                 date of execution of this Agreement;

         4.1.2   -$100,000 (one hundred thousand dollars) due upon initiation
                 of the first Phase I/II IND (Investigational New Drug
                 application) clinical trials for any indication;

         4.1.3   -$350,000 (three hundred and fifty thousand dollars) due upon
                 completion of a Phase II clinical trials for any indication;
                 and

         4.1.4   -$500,000 (five hundred thousand dollars) due upon submission
                 of a PLA (Product License Application) or NDA (New Drug
                 Application) for any indication.





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The information below marked by [****] has been omitted pursuant to a request
for confidential treatment. The omitted portion has been seperately filed with
the Commission.

4.2      A royalty based on the Net Sales Price of the Licensed  Products or
         Licensed Processes used, leased or sold by LICENSEE or a joint venture
         in which LICENSEE is involved, which said royalty shall be [****]
         of Net Sales Price.

4.3      Where sublicenses have been granted or strategic partnerships entered
         into, EntreMed shall pay to CMCC [****] of any and all sublicensing
         payments.  Sublicensing payments are defined as any and all payments
         made to EntreMed by the Sublicensee or strategic partner except for
         payments to support research and development conducted by EntreMed,
         for purchases of equity or for payments for goods and services.
         EntreMed shall pay to CMCC [****] of the royalty income paid to
         EntreMed up to $100,000,000 of cumulative Net Sales of the Licensed
         Product and, after $100,000,000 of cumulative Net Sales, EntreMed
         shall pay to CMCC [****] of royalty payments to EntreMed from the
         Sublicensee with a minimum of [****] of net sales of the Licensed
         Product made by the Sublicensee.

4.4      No multiple royalties shall be payable because any Licensed Product,
         its manufacture, use, lease or sale are or shall be covered by more
         than one Patent Rights Patent Application or Patent Rights Patent
         licensed under this Agreement.

4.5      Royalty payments shall be paid in United States dollars in Boston,
         Massachusetts, or at such other place as CMCC may reasonably designate
         consistent with the laws and regulations controlling in any foreign
         country. If any currency conversion shall be required in connection
         with the payment of royalties hereunder, such conversion shall be made
         by using the exchange rate prevailing at the Bank of Boston on the
         last business day of the calendar quarterly reporting period to which
         such royalty payments relate.

                        ARTICLE V -- REPORTS AND RECORDS

5.1      LICENSEE shall keep full, true and accurate books of account
         containing all particulars that may be necessary for the purpose of
         showing the amounts payable to CMCC hereunder. Said books of account
         shall be kept at LICENSEE's principal place of business or the
         principal place of business of the appropriate Division of





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         LICENSEE to which this Agreement relates. Said books and the
         supporting data shall be open at all reasonable times for five (5)
         years following the end of the calendar year to which they pertain, to
         the inspection of CMCC or its agents for the purpose of verifying
         LICENSEE's royalty statement or compliance in  other respects with
         this Agreement. CMCC can request auditing of said books and supporting
         data no more than once each calendar year.

5.2.     LICENSEE, within forty-five (45) days after the initial sale or
         sublicense of the product on  March 31, June 30, September 30 and
         December 31, of each year, shall deliver to CMCC true and accurate
         reports, giving such particulars of the business conducted by LICENSEE
         and its sublicensees during the preceding three month period under
         this Agreement as shall be pertinent to a royalty accounting
         hereunder. These shall include at least the following:

         5.2.1   Number of Licensed Products manufactured and sold.

         5.2.2   Total billings for Licensed Products sold.

         5.2.3   Accounting for all Licensed Products used or sold.

         5.2.4   Deductions applicable as provided in Paragraph 1.7

         5.2.5   Total royalties due.

         5.2.6   Names and addresses of all sublicensees of LICENSEE.

5.3      With each such report submitted, LICENSEE shall pay to CMCC the
         royalties due and payable under this Agreement. If no royalties shall
         be due after the initial sublicense agreement or sale, LICENSEE shall
         so report. On or before the ninetieth (90th) day following the close
         of LICENSEE's fiscal year, LICENSEE shall provide CMCC with LICENSEE's
         certified financial statements for the preceding fiscal year
         including, at a minimum, a Balance Sheet and an Operating Statement.

5.4      The royalty payments set forth in this Agreement shall, if overdue,
         bear interest until payment at a per annum rate of two percent (2%)
         above the prime rate in effect at the Bank of Boston on the due date.
         The payment of such interest shall not foreclose CMCC from exercising
         any other rights it may have as a consequence of the lateness of any
         payment.





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                        ARTICLE VI -- PATENT PROSECUTION

6.1      CMCC and LICENSEE shall apply for, seek prompt issuance of, and
         maintain during the term of this Agreement the Patent Rights set forth
         in Appendix A. The prosecution, filing and maintenance of all Patent
         Rights Patents and Applications shall be the primary responsibility of
         LICENSEE; with appropriate and timely review and approval by CMCC.
         LICENSEE shall solicit CMCC's comment prior to any significant actions
         required  during filing, prosecution, and maintenance and provide CMCC
         with drafts of proposed actions and responses in advance and file
         copies after the action is completed.  If CMCC elects to consult with
         patent attorneys more than is considered necessary and reasonable by
         LICENSEE, such consultation shall be at CMCCGs expense.

6.2      Payment of all fees and costs relating to the filing, prosecution, and
         maintenance of the Patent Rights shall be the responsibility of
         LICENSEE, whether such fees and costs were incurred before or after
         the date of this Agreement.

                           ARTICLE VII - INFRINGEMENT

7.1      LICENSEE shall inform CMCC promptly in writing of any alleged
         infringement of the Patent Rights by a third party and of any
         available evidence thereof.

7.2      If at any time during the term of this Agreement, LICENSEE furnishes
         to CMCC reasonably convincing written evidence of an infringement of a
         patent included in the Patent Rights covering the Inventions which
         adversely and substantially affects the commercial operations of
         LICENSEE in the country where the infringement of the patent is
         occurring, under the license granted hereunder, and CMCC shall within
         three (3) months after receipt of such evidence (the three month
         period) fail to cause such infringement to terminate or to bring a
         suit or action to compel termination, then payment of one half (1/2)
         the royalties and one half (1/2) minimum  amounts which are earned and
         payable to CMCC on Net Sales by licensee or sublicensees under Article
         IV hereof shall be waived in the country of the infringement, so long
         as such infringement continues; provided, however, that such royalties
         and minimum  amounts shall not be waived so long as at least one suit
         or action is being prosecuted by CMCC for infringement of a patent in
         the country in which the infringement of the patent is occurring,
         covering the





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         Inventions.  In no event shall such waiver of royalties and minimum
         amounts exceed 50% of the royalties and minimum amounts payable
         hereunder.

7.3      If after the three month period, CMCC fails to cause such infringement
         to terminate or to bring a suit or action to compel termination,
         LICENSEE shall have the right, but not the obligation, to bring such
         suit or action to compel termination at LICENSEE's expense.  CMCC
         independently shall have the right to join any such suit or action
         brought by LICENSEE and, in such  event.   No settlement, consent
         judgment or other voluntary final disposition of the suit may be
         entered into without the consent of CMCC which consent shall not
         unreasonably be withheld.   Any damages recovered by suit or action
         shall be first used to reimburse each party hereto for the cost of
         such suit or action (including attorney's fees) actually paid by each
         party hereto as the case may be, then to reimburse CMCC for any
         royalties and minimum royalties waived under this Section 7.3 and the
         residue, if any, shall be belong to the party responsible for the
         prosecution of the suit.

7.4      In the event that LICENSEE shall undertake the enforcement and/or
         defense of the Patent Rights by litigation, LICENSEE may withhold up
         to fifty percent (50%) of the royalties otherwise thereafter due CMCC
         hereunder and apply the same toward reimbursement of its expenses,
         including reasonable attorneys' fees, in connection therewith. Any
         recovery of damages by LICENSEE for any such suit shall be applied
         first in satisfaction of any unreimbursed expenses and legal fees of
         LICENSEE relating to the suit, next toward reimbursement of CMCC for
         any royalties past due or withheld and applied pursuant to this
         Article VII, and to royalties due to CMCC for infringing sales as if
         sales had been made by LICENSEE. The balance remaining from any such
         recovery shall belong to LICENSEE.

7.5      In the event that a declaratory judgment action alleging invalidity or
         non-infringement of any of the Patent Rights shall be brought against
         LICENSEE, CMCC, at its option, shall have the right, within thirty
         (30) days after commencement of such action, to intervene and take
         over the sole defense of the action at its own expense.





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7.6      If, for any reason, LICENSEE should choose not undertake the
         enforcement and/or defense of the Patent Rights by litigation after
         the three month period, CMCC shall have the right, but not the
         obligation, to prosecute, at its own expense, any such infringements
         of the Patent Rights and, in furtherance of such right, CMCC hereby
         agrees that LICENSEE may join CMCC as a party plaintiff in any such
         suit, without expense to LICENSEE.  The total cost of any such
         infringement action commenced or defended solely by CMCC shall be
         borne by CMCC and CMCC shall keep any recovery or damages for past
         infringement derived therefrom.

7.7      In any infringement suit as either party may institute to enforce the
         Patent Rights pursuant to this  Agreement, the other party hereto
         shall, at the request and the expense of the party initiating such
         suit, cooperate in all respects and, to the extent possible, have its
         employees testify when requested and make available relevant records,
         papers, information, samples, specimens, and the like.

7.8      LICENSEE, during the period of this Agreement, shall have the sole
         right in accordance with the terms and conditions herein to sublicense
         any alleged infringer for future use of the Patent Rights.

        ARTICLE VIII - INDEMNIFICATION, PRODUCT LIABILITY AND INSURANCE

8.1.     Indemnification

         8.1.1   LICENSEE shall indemnify, defend and hold harmless CMCC and
                 its trustees, officers, medical and professional staff,
                 employees, and agents and their respective successors, heirs
                 and assigns (the "Indemnitees"), against any liability,
                 damage, loss or expense (including reasonable attorney's fees
                 and expenses of litigation) incurred by or imposed upon the
                 Indemnitees or any one of them in connection with any claims,
                 suits, actions, demands or judgments arising out of any theory
                 of product liability (including, but not limited to, actions
                 in the form of tort, warranty, or strict liability) concerning
                 any product, process or service made, used or sold pursuant to
                 any right or license granted under this Agreement.





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         8.1.2   LICENSEE's indemnification under (a) above shall not apply to
                 any liability, damage, loss or expense to the extent that it
                 is directly attributable to the negligent activities, reckless
                 misconduct or intentional misconduct of the Indemnitees.

         8.1.3   LICENSEE agrees, at its own expense, to provide attorneys
                 reasonably acceptable to CMCC to defend against any actions
                 brought or filed against any party indemnified hereunder with
                 respect to the subject of indemnity contained herein, whether
                 or not such actions are rightfully brought.

         8.1.4   CMCC shall indemnify, defend and hold harmless Licensee for
                 any damage, loss or expense to the extent that it is directly
                 attributable to the negligent activities, reckless misconduct,
                 or  intentional misconduct of the employees or subcontractors
                 of CMCC.

         8.1.5   This Section 8.1 shall survive expiration or termination of
                 this Agreement.

8.2.     Insurance

         8.2.1   Beginning at the time as any such product, process or service
                 is being commercially distributed or sold (other than for the
                 purpose of obtaining regulatory approvals) by LICENSEE or by a
                 sublicensee, affiliate or agent of LICENSEE, LICENSEE shall,
                 at its sole cost and expense, procure and maintain
                 comprehensive general liability insurance in amounts not less
                 than $2,000,000 per incident and $2,000,000 annual aggregate
                 and naming the Indemnitees as additional insureds. Such
                 comprehensive general liability insurance shall provide

                 8.2.1.1  product liability coverage and

                 8.2.1.2  broad form contractual liability coverage for
                          LICENSEE's indemnification under Section 8.1 of this
                          Agreement. If LICENSEE elects to selfinsure all or
                          part of the limits described





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                          above (including deductibles or retentions which are
                          in excess of $250,000 annual aggregate) such
                          self-insurance program must be acceptable to the CMCC
                          and the Risk Management Foundation of the Harvard
                          Medical Institutions, Inc. The minimum amount of
                          insurance coverage required under this Section 8.2
                          shall not be construed to create a limit of
                          LICENSEE's liability with respect to its
                          indemnification under Section 8.1 of this Agreement.

         8.2.2   LICENSEE shall provide CMCC with written evidence of such
                 insurance upon request of CMCC. LICENSEE shall provide CMCC
                 with written notice at lease forty-five (45) days prior to any
                 material change  in such insurance.  If the insurnace is
                 canceled and if LICENSEE does not obtain replacement insurance
                 providing comparable coverage within such forty-five (45) day
                 period, CMCC shall have the right to terminate this Agreement
                 effective at the end of such forty-five (45) day period after
                 providing notice of CMCC's intent to do so.

         8.2.3   LICENSEE shall maintain such comprehensive general liability
                 insurance during

                 8.2.3.1  the period that any such product, process or service
                          is being commercially distributed or sold (other than
                          for the purpose of obtaining regulatory approvals) by
                          LICENSEE or by a sublicensee, affiliate or agent of
                          LICENSEE, and

                 8.2.3.2  a reasonable period after the period referred to in
                          8.2.3.1 above which in no event shall be less than
                          five (5) years.

         8.2.4   This ARTICLE 8.2 shall survive expiration or termination of
                 this Agreement.





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                         ARTICLE IX -- EXPORT CONTROLS

         It is understood that CMCC is subject to United States laws and
         regulations controlling the export of technical data, computer
         software, laboratory prototypes and other commodities (including the
         Arms Export Control Act, as amended and the Export Administration Act
         of 1979), and that its obligations hereunder are contingent on
         compliance with applicable United States export laws and regulations.
         The transfer of certain technical data and commodities may require a
         license from the cognizant agency of the United States Government
         and/or written assurances by LICENSEE that LICENSEE shall not export
         data or commodities to certain foreign countries without prior
         approval of such agency. CMCC neither represents that a license shall
         not be required nor that, if required, it shall be issued.

                         ARTICLE X -- NON-USE OF NAMES

         LICENSEE shall not use the names of the Children's Medical Center
         Corporation nor of any of its employees, nor any adaptation thereof,
         in any advertising, promotional or sales literature without prior
         written consent obtained from CMCC in each case except that LICENSEE
         may state that it is licensed by CMCC under one or more of the patents
         and/or applications comprising the Patent Rights, and LICENSEE may
         comply with disclosure requirements of all applicable laws relating to
         its business, including United States and state security laws.

                            ARTICLE XI -- ASSIGNMENT

         Subject to the restrictions set forth herein, this  Agreement, and
         each and every provision hereof, shall be binding upon and shall inure
         to the benefit of the parties, their respective successors,
         successors-in-title, heirs and assigns, and each and every
         successor-in-interest to any party, whether such successor acquires
         such interest by way of gift, inheritance, purchase, foreclosure, or
         by any other method, shall hold such interest subject to all the terms
         and provisions of this Agreement; provided however that LICENSEE shall
         not assign or transfer the whole or any part of this Agreement or its
         rights hereunder without the express written agreement of CMCC which
         agreement shall not be unreasonably withheld.





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                           ARTICLE XII -- ARBITRATION

12.1     Any and all claims, disputes or controversies arising under, out of,
         or in connection with this Agreement, which have not been resolved by
         good faith negotiations between the parties, shall be resolved by
         final and binding arbitration in Boston, Massachusetts, under patent
         arbitration rules of the American Arbitration Association then
         obtaining. The arbitrators shall have no power to add to, subtract
         from or modify any of the terms or conditions of this Agreement. Any
         award rendered in such arbitration may be enforced by either party in
         either the courts of the Commonwealth of Massachusetts or in the
         United States District Court for the District of Massachusetts, to
         whose jurisdiction for such purposes CMCC and LICENSEE each hereby
         irrevocably consents and submits.

12.2     Notwithstanding the foregoing, nothing in this Article shall be
         construed to waive any rights or timely performance of any obligations
         existing under this Agreement.

                      ARTICLE XIII -- TERM AND TERMINATION

13.1     Unless earlier terminated as hereinafter provided, this Agreement
         shall remain in full force and effect for the life of the last to
         expire patent issued under the Patent Rights.

13.2     If LICENSEE shall cease to carry on its business, this Agreement shall
         terminate upon notice by CMCC.

13.3     Should LICENSEE fail to pay CMCC royalties due and payable hereunder,
         CMCC shall have the right to terminate this Agreement on sixty (60)
         days' notice, unless LICENSEE shall pay CMCC within the sixty (60) day
         period, all such royalties and interest due and payable. Upon the
         expiration of the sixty (60) day  period, if LICENSEE shall not have
         paid all such royalties and interest due and payable, the rights,
         privileges and license granted hereunder shall terminate.

13.4     Upon any material breach or default of this Agreement by LICENSEE,
         other than those occurrences set out in Paragraphs 13.2 and 13.3
         herein above, which shall always take precedence in that order over
         any material breach or default referred to in this Paragraph 13.3,
         CMCC shall have the right to terminate this Agreement





                                       16
<PAGE>   18
         and the rights, privileges and license granted hereunder by ninety
         (90) days' notice to LICENSEE. Such termination shall become effective
         unless LICENSEE shall have cured any such breach or default prior to
         the expiration of the ninety (90) day period.

13.5     LICENSEE shall have the right to terminate this Agreement at any time
         on six (6) months' notice to CMCC, and upon payment of all amounts due
         CMCC through the effective date of termination.

13.6     Upon termination of this Agreement for any reason, nothing herein
         shall be construed to release either party from any obligation that
         matured prior to the effective date of such termination. LICENSEE and
         any sublicensee thereof may, however, after the effective date of such
         termination, sell all Licensed Products, and complete Licensed
         Products in the process of manufacture at the time of such termination
         and sell the same, provided that LICENSEE shall pay to CMCC the
         royalties thereon as required by Article IV of this Agreement and
         shall submit the reports required by Article V hereof on the sales of
         Licensed Products.

13.7     CMCC agrees that if LICENSEE has provided to CMCC notice that LICENSEE
         has granted a sublicense to a sublicensee under this Agreement, then
         in the event CMCC terminates this Agreement for any reason, CMCC shall
         provide to such sublicensee no less than thirty (30) days prior to the
         effective date of said termination, written notice of said termination
         at the address specified by LICENSEE to CMCC in LICENSEE's notice to
         CMCC under Article XIV. CMCC agrees that upon the sublicensee's notice
         as described below and provided the sublicensee is not in breach of
         its sublicense, CMCC shall grant to such sublicensee license rights
         and terms equivalent to the sublicense rights and terms which the
         sublicense shall have granted to said sublicensee; provided that the
         sublicensee shall remain a sublicensee under this  Agreement for a
         period of at least sixty (60) days following receipt of notice from
         CMCC. Sublicenses shall during said sixty (60) day period provide to
         CMCC notice wherein the sublicensee;

         13.7.1  reaffirms the terms and conditions of this Agreement as it
                 relates to the rights the sublicensee has been granted under
                 the sublicense;





                                       17
<PAGE>   19
         13.7.2  agrees to abide by all of the terms and conditions of this
                 Agreement applicable to sublicensees and to discharge directly
                 all pertinent obligations of LICENSEE which LICENSEE is
                 obligated hereunder to discharge excluding any financial
                 obligations; and

         13.7.3  acknowledges that CMCC shall have no obligations to the
                 sublicensee other than its obligations set forth in this
                 Agreement with regard to LICENSEE.


           ARTICLE XIV -- PAYMENTS, NOTICES, AND OTHER COMMUNICATIONS

Any payment, notice or other communication pursuant to this Agreement shall be
sufficiently made or given on the date of the mailing if sent to such party by
certified first class mail, postage prepaid, addressed to it at its address
below or as it shall designate by written notice given to the other party:

In the case of CMCC:

         Director, Technology Transfer Office
         Office of Research Administration
         THE CHILDREN'S HOSPITAL
         300 Longwood Avenue
         Boston, MA 02115

In the case of LICENSEE:

         John W. Holaday, Ph.D.
         Chief Executive Officer
         ENTREMED, INC.
         9610 Medical Center Drive, Suite 200
         Rockville, MD 20850





                                       18
<PAGE>   20
With copy to:

         James Dean Johnson, Ph.D.
         JONES & ASKEW
         37th Floor
         191 Peachtree Street
         Atlanta, GA 30303

                     ARTICLE XV -- MISCELLANEOUS PROVISIONS

15.1     This Agreement shall be construed, governed, interpreted and applied
         in accordance with the laws of the Commonwealth of Massachusetts,
         U.S.A., except that questions affecting the construction and effect of
         any patent shall be determined by the law of the country in which the
         patent was granted.

15.2     The parties hereto acknowledge that this Agreement sets forth the
         entire Agreement and understanding of the parties hereto as to the
         subject matter hereof, and shall not be subject to any change or
         modification except by the execution of a written instrument
         subscribed to by the parties hereto.

15.3     The provisions of this Agreement are severable, and in the event that
         any provisions of this Agreement shall be determined to be invalid or
         unenforceable under any controlling body of law, such invalidity or
         unenforceability shall not in any way affect the validity or
         enforceability of the remaining provisions hereof.

15.4     LICENSEE agrees to mark the Licensed Products sold in the United
         States with all applicable United States patent numbers.  All Licensed
         Products shipped to or sold in other countries shall be marked in such
         a manner as to conform with the patent laws and practice of the
         country of manufacture or sale.

15.5     The failure of either party to assert a right hereunder or to insist
         upon compliance with any term or condition of this Agreement shall not
         constitute a waiver of that right or excuse a similar subsequent
         failure to perform any such term or condition by the other party.





                                       19
<PAGE>   21
         IN WITNESS WHEREOF this Agreement has been executed in duplicate on
behalf of the parties hereto by their respective authorized officers as of the
date first written above.

CHILDREN'S MEDICAL CENTER CORPORATION

Name     /s/  William New        
         ---------------------------------------

Title    Vice President, Research Administration
         ---------------------------------------

Date     Novmeber 29, 1996

ENTREMED, INC.

Name     /s/ John W. Holaday, PhD.        
         ---------------------------------------

Title    Chairman, CEO and President

Date     December 5, 1996





                                       20
<PAGE>   22
                                  Appendix A


CMCC No.:     474
Inventors:    J. Folkman, M. O'Reilly
Title:        Endostatin: an Endogenous Inhibitor of Angiogenesis and Tumor
              Growth
Filings:

<TABLE>
<CAPTION>
Country          Date Filed       Serial No.       Type             Jones and Askew Ref. No.
-------          ----------       ----------       ----             ------------------------
<S>              <C>              <C>              <C>              <C>
USA              10/23/95         60/005,835       Provsnl          05213-0220P
USA              8/2/96           tbd              Provsnl          05213-0221P
USA              10/22/96         tbd              Parent           05213-0223
PCT              10/22/96         tbd              Internatl        05213-0223WP
</TABLE>





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