Document:

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                                                                   Exhibit 10.21

                            THIRD AMENDMENT TO LEASE

      This THIRD AMENDMENT TO LEASE is made by and between David E. Clem and
David M. Roby, Trustees of Fort Washington Realty Trust under Declaration of
Trust dated June 19, 1995 and recorded with the Middlesex County (South
District) Registry of Deeds in Book 25422, Page 360 (the "Landlord") and Vertex
Pharmaceuticals Incorporated (the "Tenant").

      Reference is hereby made to that certain lease dated March 3, 1995, by and
between Landlord's predecessor, Fort Washington Limited Partnership and Tenant
with respect to a portion of the property (the "Premises") located at 40 Erie
Street, Cambridge, Massachusetts (the "Building"), as more particularly
described in the lease, as amended by a First Amendment to Lease (the "First
Amendment") and a Second Amendment to Lease (the "Second Amendment"). The
lease, First Amendment to Lease and Second Amendment to Lease are herein
collectively referred to as the "Lease".

      WHEREAS, the Tenant has requested, and the Landlord has agreed, to further
amend the Lease upon the terms and conditions set forth in this Third Amendment
to Lease.

      WHEREAS, Landlord and Tenant desire to amend and modify the terms of the
Lease and to ratify and confirm the terms of the Lease as amended by the First
Amendment and the Second Amendment as more particularly set forth below.

      NOW, THEREFORE, in consideration of the mutual promises herein contained,
and other good and valuable consideration, the receipt and legal sufficiency of
which is hereby acknowledged, Landlord and Tenant agree as follows:

      1. Each capitalized term which is used but not defined herein shall have
the respective meaning ascribed thereto in the Lease.

      2. Section 1 of the Second Amendment (other than the last sentence
thereof) is hereby deleted in its entirety.

      3. Effective as of October 1, 1998 (the "Effective Date"), the definition
of the Premises set forth in the Lease shall be amended to include the addition
of 41,132 r.s.f. of space (the "Additional Space") in the Building currently
leased to Millennium Pharmaceuticals, Inc. ("Millennium"). See Exhibit A to the
Second Amendment for the layout of the Additional Space.

      4. The first paragraph of Section 2 of the Second Amendment is hereby
deleted in its entirety and the following is inserted in place thereof:

      The term "Additional Space Term" as used in the Lease shall mean the
      period commencing on the Effective Date and terminating on March 18, 2009.

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      5. Section 5 of the Second Amendment is hereby deleted in its entirety and
the following is inserted in place thereof:

            5. Commencing on the Effective Date and continuing throughout the
      Additional Space Term, Tenant shall pay to Landlord Annual Fixed Rent for
      the Additional Space in the amount of $1,460,186.00 ($35.50 per r.s.f.),
      subject to adjustment as set forth in the Lease, including Sections 2 and
      6 of the Second Amendment. The Annual Fixed Rent for the Additional Space
      shall be payable in equal monthly installments in advance on the first day
      of each month and pro-rated for any portion of a calendar month during the
      Additional Space Term. In accordance with the foregoing, Tenant shall pay
      $121,682.17 to Landlord on October 1, 1998 and on the first day of each
      month thereafter until adjustment of Annual Fixed Rent for the Additional
      Space as set forth in the Lease.

      6. Commencing on the Effective Date and continuing to and including March
18, 1999 (the "Parking Term"), Landlord hereby leases to Tenant and Tenant
hereby from Landlord one hundred twenty (120) parking spaces ("Tenant's
Additional Parking Spaces") on the Lot upon the terms and conditions hereinafter
set forth. Tenant shall pay to Landlord as Additional Rent, together with the
payments of Annual Fixed Rent for the Additional Space, $75.00 per month for
each of Tenant's Additional Parking Spaces, which amount shall be prorated for
the month of March, 1999. Tenant shall have the right to sublease any of
Tenant's Additional Parking Spaces to Millennium without the consent of
Landlord, but Tenant shall remain liable for the monthly rental fee for Tenant's
Additional Parking Spaces. Landlord reserves the right from time to time to
alter or relocate any or all of Tenant's Additional Parking Spaces on or off the
Lot, provided that the total number of parking spaces available to Tenant on or
off the Lot is not decreased and any of Tenant's Additional Parking Spaces
relocated off the Lot are located within one thousand (1000) feet of the
Building, provided, however, that upon completion of construction by Landlord of
the garage at 47 Erie Street, Cambridge, Massachusetts (the "Garage"), the
completion of which is expected by March, 1999, any of Tenant's Additional
Parking Spaces which have been relocated shall be located in the Garage for the
remainder, if any, of the Parking Term.

      7. Landlord hereby represents and warrants that Landlord and Millennium
have terminated Millennium's lease of the Additional Space and Tenant's
Additional Parking Spaces effective as of the Effective Date.

      8. Anything in the Lease to the contrary notwithstanding (i) Landlord
shall have no obligation to evict Millennium from the Additional Space or
Tenant's Additional Parking Spaces or to dispossess Millennium thereof, (ii)
Tenant may sublet all or such portion of the Additional Space to Millennium for
the period commencing on the Effective Date and terminating on such date within
the Term as Tenant and Millennium may agree and on such other terms and
conditions as are consistent with and not in violation of the Lease and as
Tenant otherwise may deem acceptable, (iii) Tenant may sublet all or such number
of

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Tenant's Additional Parking Spaces to Millennium for the period commencing on
the Effective Date and terminating on or before March 18, 1999 and on such other
terms and conditions as are consistent with and not in violation of the Lease,
and (iv) any parking spaces subleased by Tenant to Millennium for any period
after March 18, 1999 shall consist of parking spaces leased to Tenant pursuant
to the Lease and shall not consist of any of Tenant's Additional Parking Spaces.

      9. Landlord shall have no liability or obligation to Tenant or Millennium
with respect to the matters set forth in a letter dated February 5, 1998 from
Tenant to Mr. Dan Winny and a letter dated February 20, 1998 from Landlord to
Millennium, copies of which are attached hereto as Exhibits A and B
respectively, and incorporated herein by reference thereto, including without
limitation, any work performed by or on behalf of Millennium with respect to the
Additional Space, the restoration thereof and the replacement and/or storage of
fixtures removed from the Additional Space by Millennium, and Tenant hereby
releases Landlord from all such liabilities and obligations.

      10. The Lease, as amended hereby, is hereby ratified and confirmed in all
respects.

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      Executed as of the 1st day of October, 1998.

                                        LANDLORD:

                                        FORT WASHINGTON REALTY TRUST

                                        /s/ David E. Clem, Trustee
                                        ----------------------------------------
                                        David E. Clem, Trustee and not
                                        individually

                                        FORT WASHINGTON REALTY TRUST

                                        /s/ David M. Roby
                                        ----------------------------------------
                                        David M. Roby, Trustee and not
                                        individually

                                        TENANT:

                                        VERTEX PHARMACEUTICALS INCORPORATED

                                        By: /s/ Richard H. Aldrich
                                            ------------------------------------
                                        Name: Richard H. Aldrich
                                        Title: Senior Vice President<PAGE>
                                                                   Exhibit 10.22

                            FOURTH AMENDMENT TO LEASE

      This FOURTH AMENDMENT TO LEASE (this "Fourth Amendment") is executed by
and between David E. Clem and David M. Roby, Trustees of Fort Washington Realty
Trust under Declaration of Trust dated June 19, 1995 and recorded with the
Middlesex County (South District) Registry of Deeds (the "Registry") in Book
25422, Page 360 and filed with the Middlesex South Registry District of the Land
Court (the "Registry District") as Document No. 976230 (the "Landlord") and
Vertex Pharmaceuticals Incorporated (the "Tenant").

      Reference is hereby made to that certain lease dated March 3, 1995, by and
between Landlord's predecessor, Fort Washington Limited Partnership, and Tenant
with respect to a portion of the property (the "Premises") located at 40 Erie
Street, Cambridge, Massachusetts (the "Building"), as more particularly
described in the lease, as amended by a First Amendment to Lease (the "First
Amendment"), a Second Amendment to Lease (the "Second Amendment") and a Third
Amendment to Lease (the "Third Amendment"). The lease, First Amendment, Second
Amendment and Third Amendment are herein collectively referred to as the
"Lease".

      WHEREAS, Landlord and Tenant desire to amend and modify the terms of the
Lease and to ratify and confirm the terms of the Lease as amended by the First
Amendment, the Second Amendment and the Third Amendment, as more particularly
set forth below.

      NOW, THEREFORE, in consideration of the mutual promises herein contained,
and other good and valuable consideration, the receipt and legal sufficiency of
which is hereby acknowledged, Landlord and Tenant agree as follows:

      1. Each capitalized term which is used but not defined herein shall have
the respective meaning ascribed thereto in the Lease.

      2. The definition of "Lot" as set forth in Section 1.1 of the Lease is
hereby deleted and the following definition is hereby inserted in place thereof:

            The Land shown on Exhibit A-1 to this Fourth Amendment as the "Fort
            Washington Premises" and more particularly described on Exhibit A-2
            to this Fourth Amendment, both of which are attached hereto and
            incorporated herein by reference thereto.

      3. Anything in the Lease to the contrary notwithstanding, references in
the Lease to "Exhibit A-1" or "Exhibit A-2", including Section 1.2 of the Lease,
shall mean Exhibit A-1 attached hereto and Exhibit A-2 attached hereto,
respectively.

      4. Simultaneously with the execution hereof, Landlord and Tenant shall
execute, acknowledge and deliver an Amended Notice of Lease in the form of
Exhibit B

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attached hereto, which Landlord agrees to record with the Registry and file
with the Registry District.

      5. The Lease, as amended hereby, is hereby ratified and confirmed in all
respects.

      Executed under seal as of the 21 day of February, 2000.

                                        LANDLORD:

                                        FORT WASHINGTON REALTY TRUST

                                        /s/ David E. Clem, Trustee
                                        ----------------------------------------
                                        David E. Clem, Trustee
                                        and not individually

                                        /s/ David M. Roby
                                        ----------------------------------------
                                        David M. Roby Trustee and not
                                        individually

                                        TENANT:

                                        By: /s/ Richard H. Aldrich
                                            ------------------------------------
                                        Name: Richard H. Aldrich
                                        Title: Senior Vice-President, Chief
                                               Business Officer

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