Document:

052001 S8 Plan

Exhibit 4.1

RATIONAL SOFTWARE CORPORATION
1997 SUPPLEMENTAL STOCK PLAN

(As Amended in April 2001)

1.Purposes of the Plan.  The purposes of this Supplemental Stock
Plan are:

- to attract and retain the best available personnel for positions of substantial responsibility, 

- to provide additional incentive to Employees, Directors and Consultants, and 

- to promote the success of the Company's business.  

Options granted under the Plan will be Nonstatutory Stock Options.  

2.Definitions.  As used herein, the following definitions shall apply:

(a)"Administrator" means the Board or any of its Committees as shall be administering the Plan, in
accordance with Section 4 of the Plan.

(b)"Applicable Laws" means the requirements relating to the administration of stock option plans under
U. S. state corporate laws, U.S. federal and state securities laws, the Code, any stock exchange or quotation system on which the
Common Stock is listed or quoted and the applicable laws of any foreign country or jurisdiction where Options are, or will be,
granted under the Plan.

(c)"Board" means the Board of Directors of the Company.

(d)"Code" means the Internal Revenue Code of 1986, as amended.

(e)"Committee"  means a committee of Directors appointed by the Board in accordance with Section 4
of the Plan.

(f)"Common Stock" means the Common Stock of the Company.

(g)"Company" means Rational Software Corporation, a Delaware corporation.

(h)"Consultant" means any person, including an advisor, engaged by the Company or a Parent or
Subsidiary to render services to such entity.

(i)"Director" means a member of the Board.

(j)"Disability" means total and permanent disability as defined in Section 22(e)(3) of the Code.

(k)"Employee" means any person, excluding any Officer or Director, employed by the Company or any
Parent or Subsidiary of the Company.  An Employee shall not cease to be a Service Provider (as defined herein) in the case of
(i) any leave of absence approved by the Company or (ii) transfers between locations of the Company or between the Company,
its Parent, any Subsidiary, or any successor. 

(l)"Exchange Act" means the Securities Exchange Act of 1934, as amended.

(m)"Fair Market Value" means, as of any date, the value of Common Stock determined as follows:

(i)If the Common Stock is listed on any established stock exchange or a national market system, including
without limitation the Nasdaq National Market or The Nasdaq SmallCap Market of The Nasdaq Stock Market, its Fair Market Value shall
be the closing sales price for such stock (or the closing bid, if no sales were reported) as quoted on such exchange or system for
the last market trading day prior to the time of determination, as reported in The Wall Street Journal or such other source as
the Administrator deems reliable;

(ii)If the Common Stock is regularly quoted by a recognized securities dealer but selling prices are not
reported, the Fair Market Value of a Share of Common Stock shall be the mean between the high bid and low asked prices for the Common
Stock on the last market trading day prior to the day of determination, as reported in The Wall Street Journal or such other
source as the Administrator deems reliable;

(iii)In the absence of an established market for the Common Stock, the Fair Market Value shall be determined
in good faith by the Administrator.

(n)"Notice of Grant" means a written or electronic notice evidencing certain terms and conditions of an
individual Option grant.  The Notice of Grant is part of the Option Agreement.

(o)"Officer" means a person who is an officer of the Company within the meaning of Section 16 of the
Exchange Act and the rules and regulations promulgated thereunder.

(p)"Option" means a nonstatutory stock option granted pursuant to the Plan, that is not intended to
qualify as an incentive stock option within the meaning of Section 422 of the Code and the regulations promulgated thereunder.

(q)"Option Agreement" means an agreement between the Company and an Optionee evidencing the terms and
conditions of an individual Option grant.  The Option Agreement is subject to the terms and conditions of the Plan.

(r)"Option Exchange Program" means a program whereby outstanding options are surrendered in exchange
for options with a lower exercise price.

(s)"Optioned Stock" means the Common Stock subject to an Option.

(t)"Optionee" means the holder of an outstanding Option granted under the Plan.

(u)"Parent" means a "parent corporation," whether now or hereafter existing, as defined in
Section 424(e) of the Code.

(v)"Plan" means this 1997 Supplemental Stock Plan.

(w)"Service Provider" means an Employee or Consultant.

(x)"Share" means a share of the Common Stock, as adjusted in accordance with Section 12 of the
Plan.

(y)"Subsidiary" means a "subsidiary corporation", whether now or hereafter existing, as defined in
Section 424(f) of the Code.

3.Stock Subject to the Plan.  Subject to the provisions of
Section 12 of the Plan, the maximum aggregate number of Shares which may be optioned and sold under the Plan is fifteen million and
seven hundred thousand (15,700,000) Shares.  The Shares may be authorized, but unissued, or reacquired Common Stock.  

If an Option expires or becomes unexercisable without having been exercised in full, or is surrendered pursuant to
an Option Exchange Program, the unpurchased Shares which were subject thereto shall become available for future grant or sale under
the Plan (unless the Plan has terminated).

4.Administration of the Plan.

(a)The Plan shall be administered by (A) the Board or (B) a Committee, which committee shall be
constituted to satisfy Applicable Laws. 

(b)Powers of the Administrator.  Subject to the provisions of the Plan, and in the case
of a Committee, subject to the specific duties delegated by the Board to such Committee, the Administrator shall have the authority,
in its discretion:

(i)to determine the Fair Market Value of the Common Stock;

(ii)to select the Service Providers to whom Options may be granted hereunder;

(iii)to determine whether and to what extent Options are granted hereunder;

(iv)to determine the number of shares of Common Stock to be covered by each Option granted hereunder;

(v)to approve forms of agreement for use under the Plan;

(vi)to determine the terms and conditions, not inconsistent with the terms of the Plan, of any award granted
hereunder.  Such terms and conditions include, but are not limited to, the exercise price, the time or times when Options may be
exercised (which may be based on performance criteria), any vesting acceleration or waiver of forfeiture restrictions, and any
restriction or limitation regarding any Option  or the shares of Common Stock relating thereto, based in each case on such factors as
the Administrator, in its sole discretion, shall determine;

(vii)to reduce the exercise price of any Option to the then current Fair Market Value if the Fair Market Value
of the Common Stock covered by such Option shall have declined since the date the Option was granted;

(viii)to institute an Option Exchange Program;

(ix)to construe and interpret the terms of the Plan and awards granted pursuant to the Plan;

(x)to prescribe, amend and rescind rules and regulations relating to the Plan, including rules and regulations
relating to sub-plans established for the purpose of qualifying for preferred tax treatment under foreign tax laws;

(xi)to modify or amend each Option (subject to Section 14(b) of the Plan), including the discretionary
authority to extend the post-termination exercisability period of Options longer than is otherwise provided for in the Plan;

(xii)to authorize any person to execute on behalf of the Company any instrument required to effect the grant
of an Option or  previously granted by the Administrator;

(xiii)to determine the terms and restrictions applicable to Options; 

(xiv)to allow Optionees to satisfy withholding tax obligations by electing to have the Company withhold from
the Shares to be issued upon exercise of an Option or Stock Purchase Right that number of Shares having a Fair Market Value equal to
the amount required to be withheld.  The Fair Market Value of the Shares to be withheld shall be determined on the date that the
amount of tax to be withheld is to be determined.  All elections by an Optionee to have Shares withheld for this purpose shall be
made in such form and under such conditions as the Administrator may deem necessary or advisable; and

(xv)to make all other determinations deemed necessary or advisable for administering the Plan.

(c)Effect of Administrator's Decision.  The Administrator's decisions, determinations
and interpretations shall be final and binding on all Optionees and any other holders of Options.

5.Eligibility.  Options hereunder may be granted only to Service Providers.
Options may not be granted to Officers or Directors.

6.Limitation.  Neither the Plan nor any Option shall confer upon an Optionee any
right with respect to continuing the Optionee's relationship as a Service Provider with the Company, nor shall they interfere in any
way with the Optionee's right or the Company's right to terminate such relationship at any time, with or without cause.

7.Term of Plan.  The Plan shall become effective upon its adoption by the
Board.  It shall continue in effect for ten (10) years, unless sooner terminated under Section 14 of the Plan. 

8.Term of Option.  The term of each Option shall be stated in the Option Agreement.

9.Option Exercise Price and Consideration.

(a)Exercise Price.  The per share exercise price for the Shares to be issued pursuant to exercise of an
Option shall be determined by the Administrator.

(b)Waiting Period and Exercise Dates.  At the time an Option is granted, the Administrator shall fix
the period within which the Option may be exercised and shall determine any conditions which must be satisfied before the Option may
be exercised.

(c)Form of Consideration.  The Administrator shall determine the acceptable form of consideration for
exercising an Option, including the method of payment.  Such consideration may consist entirely of:

(i)cash;

(ii)check;

(iii)promissory note;

(iv)other Shares which (A) in the case of Shares acquired upon exercise of an option, have been owned by
the Optionee for more than six months on the date of surrender, and (B) have a Fair Market Value on the date of surrender equal
to the aggregate exercise price of the Shares as to which said Option shall be exercised;

(v)consideration received by the Company under a cashless exercise program implemented by the Company in
connection with the Plan;

(vi)a reduction in the amount of any Company liability to the Optionee, including any liability attributable
to the Optionee's participation in any Company-sponsored deferred compensation program or arrangement;

(vii)such other consideration and method of payment for the issuance of Shares to the extent permitted by
Applicable Laws; or

(viii)any combination of the foregoing methods of payment.

10.Exercise of Option.

(a)Procedure for Exercise; Rights as a Shareholder. Any Option granted hereunder shall be
exercisable according to the terms of the Plan and at such times and under such conditions as determined by the Administrator and set
forth in the Option Agreement.  An Option may not be exercised for a fraction of a Share.

An Option shall be deemed exercised when the Company receives: (I) written or electronic notice of exercise (in
accordance with the Option Agreement) from the person entitled to exercise the Option, and (ii) full payment for the Shares with
respect to which the Option is exercised.  Full payment may consist of any consideration and method of payment authorized by the
Administrator and permitted by the Option Agreement and the Plan.  Shares issued upon exercise of an Option shall be issued in the
name of the Optionee or, if requested by the Optionee, in the name of the Optionee and his or her spouse.  Until the Shares are
issued (as evidenced by the appropriate entry on the books of the Company or of a duly authorized transfer agent of the Company), no
right to vote or receive dividends or any other rights as a shareholder shall exist with respect to the Optioned Stock,
notwithstanding the exercise of the Option.  The Company shall issue (or cause to be issued) such Shares promptly after the Option is
exercised.  No adjustment will be made for a dividend or other right for which the record date is prior to the date the Shares are
issued, except as provided in Section 12 of the Plan.

Exercising an Option in any manner shall decrease the number of Shares thereafter available, both for purposes of
the Plan and for sale under the Option, by the number of Shares as to which the Option is exercised.

(b)Termination of Relationship as a Service Provider.  If an Optionee ceases to be a Service
Provider, other than upon the Optionee's death or Disability, the Optionee may exercise his or her Option, but only within such
period of time as is specified in the Option Agreement, and only to the extent that the Option is vested on the date of termination
(but in no event later than the expiration of the term of such Option as set forth in the Option Agreement).  In the absence of a
specified time in the Option Agreement, the Option shall remain exercisable for three (3) months following the Optionee's
termination.  If, on the date of termination, the Optionee is not vested as to his or her entire Option, the Shares covered by the
unvested portion of the Option shall revert to the Plan.  If, after termination, the Optionee does not exercise his or her Option
within the time specified by the Administrator, the Option shall terminate, and the Shares covered by such Option shall revert to the
Plan.

(c)Disability of Optionee.  If an Optionee ceases to be a Service Provider as a result of the
Optionee's Disability, the Optionee may exercise his or her Option within such period of time as is specified in the Option
Agreement, to the extent the Option is vested on the date of termination (but in no event later than the expiration of the term of
such Option as set forth in the Option Agreement).  In the absence of a specified time in the Option Agreement, the Option shall
remain exercisable for twelve (12) months following the Optionee's termination.  If, on the date of termination, the Optionee is not
vested as to his or her entire Option, the Shares covered by the unvested portion of the Option shall revert to the Plan.  If, after
termination, the Optionee does not exercise his or her Option within the time specified herein, the Option shall terminate, and the
Shares covered by such Option shall revert to the Plan.

(d)Death of Optionee.  If an Optionee dies while a Service Provider, the Option may be
exercised within such period of time as is specified in the Option Agreement (but in no event later than the expiration of the term
of such Option as set forth in the Notice of Grant), by the Optionee's estate or by a person who acquires the right to exercise the
Option by bequest or inheritance, but only to the extent that the Option is vested on the date of death.  In the absence of a
specified time in the Option Agreement, the Option shall remain exercisable for twelve (12) months following the Optionee's
termination.  If, at the time of death, the Optionee is not vested as to his or her entire Option, the Shares covered by the unvested
portion of the Option shall immediately revert to the Plan.  The Option may be exercised by the executor or administrator of the
Optionee's estate or, if none, by the person(s) entitled to exercise the Option under the Optionee's will or the laws of descent or
distribution.  If the Option is not so exercised within the time specified herein, the Option shall terminate, and the Shares covered
by such Option shall revert to the Plan.

(e)Buyout Provisions.  The Administrator may at any time offer to buy out for a payment in cash or
Shares, an Option previously granted based on such terms and conditions as the Administrator shall establish and communicate to the
Optionee at the time that such offer is made.

11.Non-Transferability of Options .  Unless determined otherwise by the
Administrator, an Option may not be sold, pledged, assigned, hypothecated, transferred, or disposed of in any manner other than by
will or by the laws of descent or distribution and may be exercised, during the lifetime of the Optionee, only by the Optionee.  If
the Administrator makes an Option transferable, such Option shall contain such additional terms and conditions as the Administrator
deems appropriate.

12.Adjustments Upon Changes in Capitalization, Dissolution, Merger
or Asset Sale. 

(a)Changes in Capitalization.  Subject to any required action by the shareholders of the Company, the
number of shares of Common Stock covered by each outstanding Option, and the number of shares of Common Stock which have been
authorized for issuance under the Plan but as to which no Options have yet been granted or which have been returned to the Plan upon
cancellation or expiration of an Option, as well as the price per share of Common Stock covered by each such outstanding Option,
shall be proportionately adjusted for any increase or decrease in the number of issued shares of Common Stock resulting from a stock
split, reverse stock split, stock dividend, combination or reclassification of the Common Stock, or any other increase or decrease in
the number of issued shares of Common Stock effected without receipt of consideration by the Company; provided, however, that
conversion of any convertible securities of the Company shall not be deemed to have been "effected without receipt of consideration."
Such adjustment shall be made by the Board, whose determination in that respect shall be final, binding and conclusive.  Except as
expressly provided herein, no issuance by the Company of shares of stock of any class, or securities convertible into shares of stock
of any class, shall affect, and no adjustment by reason thereof shall be made with respect to, the number or price of shares of
Common Stock subject to an Option. 

(b)Dissolution or Liquidation.  In the event of the proposed dissolution or liquidation of the Company,
the Administrator shall notify each Optionee as soon as practicable prior to the effective date of such proposed transaction. The
Administrator in its discretion may provide for an Optionee to have the right to exercise his or her Option until ten (10) days prior
to such transaction as to all of the Optioned Stock covered thereby, including Shares as to which the Option would not otherwise be
exercisable.  In addition, the Administrator may provide that any Company repurchase option applicable to any Shares purchased upon
exercise of an Option shall lapse as to all such Shares, provided the proposed dissolution or liquidation takes place at the time and
in the manner contemplated.  To the extent it has not been previously exercised, an Option will terminate immediately prior to the
consummation of such proposed action.

(c)Merger or Asset Sale.  In the event of a merger of the Company with or into another corporation, or
the sale of substantially all of the assets of the Company, each outstanding Option shall be assumed or an equivalent option or right
substituted by the successor corporation or a Parent or Subsidiary of the successor corporation.  In the event that the successor
corporation refuses to assume or substitute for the Option, the Optionee shall fully vest in and have the right to exercise the
Option as to all of the Optioned Stock, including Shares as to which it would not otherwise be vested or exercisable.  If an Option
becomes fully vested and exercisable in lieu of assumption or substitution in the event of a merger or sale of assets, the
Administrator shall notify the Optionee in writing or electronically that the Option shall be fully vested and exercisable for a
period of fifteen (15) days from the date of such notice, and the Option shall terminate upon the expiration of such period.  For the
purposes of this paragraph, the Option shall be considered assumed if, following the merger or sale of assets, the option or right
confers the right to purchase or receive, for each Share of Optioned Stock, immediately prior to the merger or sale of assets, the
consideration (whether stock, cash, or other securities or property) received in the merger or sale of assets by holders of Common
Stock for each Share held on the effective date of the transaction (and if holders were offered a choice of consideration, the type
of consideration chosen by the holders of a majority of the outstanding Shares); provided, however, that if such consideration
received in the merger or sale of assets is not solely common stock of the successor corporation or its Parent, the Administrator
may, with the consent of the successor corporation, provide for the consideration to be received upon the exercise of the Option, for
each Share of Optioned Stock to be solely common stock of the successor corporation or its Parent equal in fair market value to the
per share consideration received by holders of Common Stock in the merger or sale of assets.

13.Date of Grant.  The date of grant of an Option shall be, for all purposes, the
date on which the Administrator makes the determination granting such Option, or such other later date as is determined by the
Administrator.  Notice of the determination shall be provided to each Optionee within a reasonable time after the date of such
grant.

14.Amendment and Termination of the Plan.

(a)Amendment and Termination.  The Board may at any time amend, alter, suspend or terminate the Plan.

(b)Effect of Amendment or Termination.  No amendment, alteration, suspension or
termination of the Plan shall impair the rights of any Optionee, unless mutually agreed otherwise between the Optionee and the
Administrator, which agreement must be in writing and signed by the Optionee and the Company.  Termination of the Plan shall not
affect the Administrator's ability to exercise the powers granted to it hereunder with respect to options granted under the Plan
prior to the date of such termination.

15.Conditions Upon Issuance of Shares.  

(a)Legal Compliance.  Shares shall not be issued pursuant to the exercise of an Option unless the
exercise of such Option and the issuance and delivery of such Shares shall comply with Applicable Laws and shall be further subject
to the approval of counsel for the Company with respect to such compliance.

(b)Investment Representations.  As a condition to the exercise of an Option the Company may require the
person exercising such Option  to represent and warrant at the time of any such exercise that the Shares are being purchased only for
investment and without any present intention to sell or distribute such Shares if, in the opinion of counsel for the Company, such a
representation is required.

16.Inability to Obtain Authority.  The inability of the Company to obtain authority
from any regulatory body having jurisdiction, which authority is deemed by the Company's counsel to be necessary to the lawful
issuance and sale of any Shares hereunder, shall relieve the Company of any liability in respect of the failure to issue or sell such
Shares as to which such requisite authority shall not have been obtained.

17.Reservation of Shares.  The Company, during the term of this Plan,
will at all times reserve and keep available such number of Shares as shall be sufficient to satisfy the requirements of the
Plan.EXHIBIT 10.1

                            FIRST AMENDMENT TO LEASE

          THIS AGREEMENT (hereinafter referred to as the "Amendment") made as of
the16 day of March  2001,  between  826  NEWTOWN  ASSOCIATES,  L.P.,  a Delaware
limited  partnership,  whose  address  is C/O First  Evergreen,  101  Eisenhower
Parkway, Roseland, New Jersey 07068 (hereinafter referred to as "Landlord"), and
AXCELL BIOSCIENCES CORPORATION,  a Delaware corporation (hereinafter referred to
as "Tenant"),  with offices at 826 Newtown-Yardley  Road, Newtown,  Pennsylvania
18940.

                              W I T N E S S E T H:

          WHEREAS, Tenant and Landlord's  predecessor-in-interest,  Yardley Road
Associates,  L.P.,  entered  into a Lease made as of July 23, 1999  (hereinafter
referred to as the  "Lease"),  whereby  Tenant is  presently  in  possession  of
premises  containing  approximately  9,146 gross  rentable  square feet of space
(hereinafter  referred to as the "Original Premises") in the building located at
826 Newtown Yardley Road, Newtown,  Pennsylvania (hereinafter referred to as the
"Building"); and

          WHEREAS, Tenant desires to lease additional space in the Building, and
Landlord  is willing to lease such  additional  space to Tenant on the terms and
provisions set forth in the Lease, except to the extent provided for herein; and

          WHEREAS,  the  parties  hereto  desire to amend the Lease  only in the
respects and on the conditions hereinafter stated.

          NOW, THEREFORE, Landlord and Tenant agree as follows:

          1. For purposes of this  Amendment,  capitalized  terms shall have the
meanings ascribed to them in the Lease unless otherwise defined herein.

          2. Landlord and Tenant hereby confirm that the expiration  date of the
Term with  respect to the  Original  Premises  is  currently  December  31, 2004
(hereinafter  referred to as the  "Original  Term1').  The term of the  Original
Premises shall not be extended by this Amendment.

          3.  From  and  after  the  Additional  Space   Commencement  Date  (as
hereinafter defined) and continuing through the Additional Space Expiration Date
(as hereinafter  defined),  Tenant hereby leases from Landlord  additional space
consisting  of  approximately  5,680 gross  rentable  square feet  ("hereinafter
referred  to as the  "Additional  Space")  which  Additional  Space  is shown on
Exhibit A attached hereto and made a part hereof.

<PAGE>

         4. The term for the Additional  Space  (hereinafter  referred to as the
"Additional  Space Term") shall commence on the date which is the first to occur
of (i) the date  "Landlord's  Work" (as  hereinafter  defined) in the Additional
Space is deemed  substantially  completed and possession of the Additional Space
is  delivered  to Tenant free from all  tenants,  occupants  and their  personal
property, or the date Landlord would have substantially  completed and delivered
possession of the Additional Space to Tenant but for any reason  attributable to
Tenant;  and (ii) the date upon which the Additional Space is occupied by Tenant
for the conduct of Tenant's business (hereinafter referred to as the "Additional
Space Commencement  Date"), and shall expire on 11:59 p.m. on the day preceeding
the fifth (5th)  anniversary of the Additional Space Rent  Commencement Date (as
hereinafter defined).

          5.  From  and  after  the  Additional  Space   Commencement  Date  and
continuing  through the expiration of the Original  Term,  the Demised  Premises
shall  be  deemed  to  include  the  Additional   Space  and  shall  consist  of
approximately  14,826 gross rentable  square feet of space and Sections 5 and 10
of the Preamble shall be deemed modified accordingly.

          6.  From  and  after  the  Additional  Space   Commencement  Date  and
continuing through the expiration of the Original Term,  Tenant's  Proportionate
Share shall be Twelve and 36/100 (12.36%) percent and Section 10 of the Preamble
shall be deemed modified accordingly.

          7. From and after the  expiration of the Original Term and  continuing
through the Additional  Space  Expiration  Date, and provided Tenant has elected
not to extend  the  Original  Term of this  Lease as set forth in Rider A to the
Lease,  the Demised  Premises shall mean the Additional Space only consisting of
approximately 5,680 gross rentable square feet of space and Sections 5 and 10 of
the preamble shall be deemed modified accordingly.

          8. From and after the  expiration of the Original Term and  continuing
through the Additional  Space  Expiration  Date, and provided Tenant has elected
not to extend  the  Original  Term of this  Lease as set forth in Rider A to the
Lease, Tenant's Proportionate Share shall be Four and 73/100 (4.73%) percent and
Section 10 of the Preamble shall be deemed modified accordingly.

          9.  From and  after  the  later to occur of (i) the  Additional  Space
Commencement  Date  and  (ii)  July  1,  2001  (hereinafter  referred  to as the
"Additional Space Rent  Commencement  Date"),  Tenant shall pay to Landlord,  in
addition  to the Fixed Basic Rent due and  payable  for the  Original  Premises,
Fixed Basic Rent for the Additional Space as follows:

                                       2
<PAGE>

--------------------------------------------------------------------------------
Period                Rate per              Annual Fixed             Monthly
                      Rentable              Basic Rent               Installment
                      Square foot           (based upon
                      (net of               twelve equal
                      operating costs       Monthly
                      and utilities)        Installments)
--------------------------------------------------------------------------------
Additional            $22.35                $126,948.00              $10,579.00
Space Rent
Commencement
Date-06/30/02
--------------------------------------------------------------------------------
07/01/02-             $22.85                $129,788.00              $10,815.67
06/30/03
--------------------------------------------------------------------------------
07/01/03-             $23.35                $132,628.00              $11,052.33
06/30/04
--------------------------------------------------------------------------------
07/01/04-             $23.85                $135,468.00              $11,289.00
06/30/05
--------------------------------------------------------------------------------
07/01/05-             $24.35                $138,308.00              $11,525.67
Additional
Space
Expiration Date
--------------------------------------------------------------------------------

                   The aforesaid  Monthly  Installments  of Fixed Basic Rent for
the  Additional  Space shall be payable in advance on or before the first day of
each calendar month commencing upon the Additional Space Rent  Commencement Date
and continuing  through the Additional Space  Expiration Date,  without set-off,
deduction, counterclaim or any previous demand therefor (except as otherwise set
forth in the Lease),  and Paragraph 7 of the Preamble and Section 6 of the Lease
shall be deemed modified  accordingly.  Landlord  acknowledges receipt, by check
subject to collection,  of the first Monthly Installment of Fixed Basic Rent due
and payable for the Additional Space.

          10. Tenant hereby  acknowledges  to Landlord that as of the Additional
Space  Commencement  Date, Tenant is leasing the Additional Space in its "AS IS"
condition as of the date hereof, except that Landlord hereby agrees to cause the
work set forth on Exhibit B annexed  hereto and made a part hereof  (hereinafter
referred to as  "Landlord's  Work") to be  performed  to the  Additional  Space.
Landlord hereby agrees to contribute  towards the cost of the preparation of the
plans and the  construction of the Landlord's Work an amount equal to the sum of
Twelve and 00/100  ($12.00)  Dollars per rentable square foot for the Additional
Space only for a total allowance not to exceed Sixty-eight  Thousand One Hundred
Sixty  and  00/100  ($68,160.00)  Dollars   (hereinafter   referred  to  as  the
"Construction Allowance").

                   Any costs in excess of the  Construction  Allowance  shall be
paid in full to  Landlord  by Tenant  immediately  upon  demand,  which shall be
deemed  Additional Rent due under the Lease and shall be subject to all remedies
for the collection of Rent pursuant to the Lease and by law. Occupancy by Tenant
or the  delivery of a  Certificate  of Occupancy  (temporary  or  permanent)  by
Landlord (if required  pursuant to local law) shall be prima facie evidence that
Landlord has  substantially  completed  all of Landlord's  Work,  subject to the
completion of such minor items as would typically be reflected in a "punchlist".

                                       3
<PAGE>

          11.  Tenant and Landlord  represent  and warrant one to the other that
Kelley &  Associates,  Inc.  (hereinafter  referred to as  "Broker") is the sole
broker which whom either party  negotiated in bringing  about this  transaction,
and Tenant and Landlord  agree to indemnify  and hold each other  harmless  (and
Tenant agrees to indemnify and hold Landlord's  mortgagee(s)  harmless) from any
and all claims of any brokers  arising out of or in connection  with any conduct
by such party inconsistent with the representations tendered by one to the other
herein.  In no event shall  Landlord's  mortgagee(s)  have any obligation to any
broker  alleged  or  determined  to  be  involved  in  this  transaction.  It is
specifically  understood and agreed that any  commission(s)  which may be due to
Broker  shall be paid by  Landlord  pursuant  to a  separate  agreement  between
Landlord and Broker.

          12. Upon  execution  of this  Amendment,  Tenant  shall  deposit  with
Landlord the sum of  Twenty-Three  Thousand  Fifty-one  and 33/100  ($23,051.33)
Dollars,  representing  security for the  Additional  Space,  and Three Thousand
Forty-eight and 67/100  ($3,048.67),  representing  additional  security for the
Original Premises,  so that Landlord shall have on hand for the remainder of the
Original Term, the total sum of Fifty-nine  Thousand Four Hundred Six and 68/100
($59,406.68)  Dollars as security  (representing two (2) Monthly Installments of
Fixed  Basic Rent for the  Original  Premises  and the  Additional  Space at the
rental  rates  payable  during  the  last  year of the  respective  terms),  and
Paragraph  11 of the  Preamble  and  Section  38 of the  Lease  shall be  deemed
modified accordingly.

                   From  and  after  the  expiration  of the  Original  Term and
continuing through the Additional Space Expiration Date, and provided Tenant has
elected not to extend the Original Term of this Lease as set forth in Rider A to
the  Lease,  Landlord  shall  have on  hand  the  sum of  Twenty-Three  Thousand
Fifty-one  and  33/100  ($23,051.33)  Dollars,  representing  security  for  the
Additional  Space and  Paragraph  11 of the Preamble and Section 38 of the Lease
shall be deemed modified accordingly.

          13. Cytogen  Corporation,  the Guarantor  under that certain  Guaranty
dated July 14, 1999,  executed in connection with the Lease, hereby ratifies and
affirms that the terms and conditions of said Guaranty  remain in full force and
effect and shall apply with respect to the terms and  provisions of the Lease as
amended by this Amendment.

          14.  Landlord  and Tenant  hereby agree that  Tenant's  right of early
termination  of the Lease as  provided  for in  Section 4 of the Lease  shall be
deemed null and void and Tenant shall have no further  right to  terminate  this
Lease pursuant to said Section 4.

          15. Nothing  contained  herein shall be deemed a waiver or exercise of
Tenant's renewal options as set forth in the Lease. The existing renewal options
for the Original Premises, if exercised,  shall include the Additional Space and
extend the Additional Space Term, and accordingly,  if exercised, the expiration
dates for the renewal terms of the Original  Premises and the  Additional  Space
shall be  coterminus  and occur on December 31, 2009 for the first  renewal term
and December 31, 2014 for the second renewal term.

                   The Rent for the Original Premises for the first renewal term
shall be  calculated  as set  forth in  Rider A to the  Lease.  The Rent for the
Additional  Space for the  period  from the  Additional  Space  Expiration  Date
through  December  31, 2009 shall be  calculated  as set forth in Rider A of the
Lease.  The Rent for the  Original  Premises  and the  Additional  Space for the
second  renewal term (e.g.  January 1, 2010 through  December 31, 2014) shall be
calculated as set forth in Rider A of the Lease.

                                       4
<PAGE>

          16. Tenant represents,  warrants and covenants that Landlord is not in
default  under  any of its  obligations  under the Lease and that to the best of
Tenant's knowledge, Tenant is not in default of any of its obligations under the
Lease and no event has occurred which, with the passage of time or the giving of
notice,  or both,  would  constitute  a  default  by either  Landlord  or Tenant
thereunder.

          17.  Landlord  represents,  warrants and covenants that to the best of
Landlord's  knowledge,  Tenant is not in  default  under any of its  obligations
under the Lease, and that to the best of Landlord's  knowledge,  Landlord is not
in default of any of its  obligations  under the Lease and no event has occurred
which,  with the  passage  of time or the  giving  of  notice,  or  both,  would
constitute a default by either Landlord or Tenant thereunder.

          18.  Except  as  modified  by this  Amendment,  the  Lease and all the
covenants,  agreements, terms, provisions and conditions thereof shall remain in
full force and  effect and are hereby  ratified  and  affirmed.  The  covenants,
agreements,  terms,  provisions and conditions contained in this Amendment shall
bind and  inure to the  benefit  of the  parties  hereto  and  their  respective
successors and assigns. In the event of any conflict between the terms contained
in this Amendment and the Lease,  the terms herein contained shall supersede and
control the obligations and liabilities of the parties.

          19.  The  submission  of  this  Amendment  for  examination  does  not
constitute a  reservation  of, or option for,  the  Additional  Space,  and this
Amendment becomes effective only upon execution and delivery thereof by Landlord
and Tenant. If required,  this Amendment is expressly  conditioned upon Landlord
receiving  the consent and  approval of  Landlord's  mortgagee  to its terms and
provisions.  If said  consent is required  but not  received,  Landlord  may, at
Landlord's  sole option,  cancel this Amendment and thereafter the parties shall
have no further obligations to each other with respect to this Amendment, except
that Tenant shall be entitled to the full refund of any and all monies delivered
to Landlord in connection with this Amendment.

                   IN WITNESS  WHEREOF,  Landlord  and Tenant have  hereunto set
their  hands  and  seals  as of the  date  and year  first  above  written,  and
acknowledge  the one to the other that they possess the  requisite  authority to
enter into this transaction and to sign this Amendment.

                                       5
<PAGE>

                                      LANDLORD:

                                    826 NEWTOWN ASSOCIATES, L.P.
                                    a Delaware limited partnership,

                                    By:   826 NEWTOWN REALTY CORP.,
                                          a Pennsylvania corporation,
                                          its sole general partner

                                          By :  /s/  Mark S. Green
                                                     Mark S. Green, President

                                      TENANT:
                                    AXCELL BIOSCIENCES CORPORATION, a
                                    DELAWARE corporation
                                    By:  /s/ Lawrence R. Hoffman
                                    Name:  Lawrence R. Hoffman
                                    Title:  Vice President & CFO

                                          GUARANTOR:

                                    CYTOGEN CORPORATION

                                    By:  /s/ Lawrence R. Hoffman
                                    Name:  Lawrence R. Hoffman
                                    Title:  Vice President & CFO

                                       6
<PAGE>

                                    EXHIBIT A

              Diagram of space at 826 Newtown Newtown-Yardley Road

                                       7
<PAGE>

                                    EXHIBIT B

(Exhibit B consists of plans prepared by JBH 3 & Associates  dated September 28,
2000, entitled "Axcell First Floor, Architectural Drawings.)

                                       8

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