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Exhibit 10.3

        CONFIDENTIAL TREATMENT REQUESTED
UNDER 17 C.R.F §§ 200.80(B)4 AND 240.24B-2

JDOA
Execution Copy (V8)
24 October 2002

AMENDED AND RESTATED

SUBSCRIPTION, JOINT DEVELOPMENT AND OPERATING AGREEMENT

ELAN CORPORATION, PLC

ELAN INTERNATIONAL SERVICES, LTD.

ISIS PHARMACEUTICALS, INC.

AND

ORASENSE LTD.

October 24, 2002

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        THIS AMENDED AND RESTATED SUBSCRIPTION, JOINT DEVELOPMENT AND OPERATING
AGREEMENT is made this 24th day of October 2002,

among:

        (1)  ELAN CORPORATION, PLC, a public limited company incorporated under
the laws of Ireland, and having its registered office at Lincoln House, Lincoln
Place, Dublin 2, Ireland ("Elan");

        (2)  ELAN INTERNATIONAL SERVICES, LTD., a private limited company
incorporated under the laws of Bermuda, and having its registered office at
Clarendon House, 2 Church St., Hamilton, Bermuda ("EIS");

        (3)  ISIS PHARMACEUTICALS, INC., a corporation incorporated under the
laws of Delaware and having its principal place of business at 2292 Faraday
Avenue, Carlsbad, CA 92008, United States of America ("Isis"); and

        (4)  ORASENSE LTD., a private limited company incorporated under the
laws of Bermuda, and having its registered office at Clarendon House, 2 Church
St., Hamilton, Bermuda ("Orasense").

RECITALS:

        Capitalized terms shall have the meanings set forth below unless
otherwise defined.

        D.    As of the date hereof, Elan (as defined below) has entered into
the Elan License Agreement with Orasense and Isis, and Isis has entered into the
Isis License Agreement with Orasense and Elan, in connection with the license to
Orasense of the Elan Intellectual Property and the Isis Intellectual Property,
respectively.

        E.    Elan and Isis have agreed to co-operate in the management of
Orasense for the research, development and Commercialization of the Product
based on their respective technologies.

        F.    Elan, EIS, Isis and Orasense are parties to that certain
Subscription, Joint Development and Operating Agreement (the "Original
Agreement") dated April 20, 1999 (the "Original Effective Date"). The parties
have agreed to enter into this Agreement for the purpose of amending and
restating the Original Agreement and recording the terms and conditions of the
joint venture and of regulating their relationship with each other and certain
aspects of the affairs of and their dealings with Orasense.

NOW IT IS HEREBY AGREED AS FOLLOWS:

CLAUSE 1

DEFINITIONS

        1.1  In this Agreement, the following terms shall, where not
inconsistent with the context, have the following meanings respectively.

        "Affiliate" shall mean, with respect to Isis or Elan, any corporation or
entity other than Orasense (and entities controlled by it) controlling,
controlled or under the common control of Isis or Elan, as the case may be, and,
with respect to Orasense, any corporation or entity under control of Orasense,
but excluding, in the case of Elan, an Elan JV. A corporation or non-corporate
entity shall be regarded as in control of another corporation if it owns or
directly or indirectly controls at least fifty percent (50%) of the voting stock
of the other corporation or (a) in the absence of the ownership of at least
fifty percent (50%) of the voting stock of a corporation or (b) in the case of a
non-corporate entity, the power to direct or cause the direction of the
management and policies of such corporation or non-corporate entity, as
applicable.

        "Agreement" shall mean this amended and restated agreement (which
expression shall be deemed to include the Recitals and the Schedules hereto).

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        "Business" shall mean the business of Orasense as described in Clause 2
and as more particularly specified in the Research Plan and such other business
as the Directors may agree from time to time in writing should be carried on by
Orasense.

        "Commercialization" shall mean the manufacture, promotion, distribution,
marketing and sale of the Products.

        "Common Stock" shall mean the common stock, par value $1.00 per share of
Orasense.

        "Common Stock Equivalents" shall mean any options, warrants, rights or
any other securities convertible, exercisable or exchangeable, in whole or in
part, for or into Common Stock.

        "Control" shall mean the ability of Elan, Isis or Orasense, as the case
may be, to grant a license or sublicense as contemplated herein without having
to obtain the prior consent of any third party or having to amend any agreement
between Elan, Isis or Orasense, as the case may be, and a third party.

        "Development Candidate" shall mean, ISIS 104838, [***] TNF-a, as more
specifically detailed in the License Agreements.

        "Development Product" shall mean any product containing as an active
ingredient the Development Candidate formulated using the Oral Platform for
humans.

        "Directors" shall mean, at any time, the directors of Orasense.

        "EIS Director" shall have the meaning set forth in Clause 7.

        "Elan Intellectual Property" shall have the meaning set forth in the
Elan License Agreement.

        "Elan License" shall have the meaning set forth in the Elan License
Agreement.

        "Elan License Agreement" shall mean the amended and restated license
agreement between Elan, Orasense and Isis, of even date herewith.

        "Elan Minority Interest" will be deemed to have occurred if at any time
after [***], Elan's ownership interest in Orasense falls below [***]

        "Encumbrance" shall mean any liens, charges, encumbrances, equities,
claims, options, proxies, pledges, security interests, or other similar rights
of any nature.

        "Exchange Act" shall mean the Securities Exchange Act of 1934, as
amended.

        "Failure to Fund" shall have the meaning set forth in Section 9.5.

        "Field" shall mean the research, development and Commercialization of
the Oral Platform for use with Oligonucleotide Drugs.

        "Financial Year" means each year commencing on January 1 (or in the case
of the first Financial Year, the date hereof) and expiring on December 31 of
each year.

        "Fully Diluted Common Stock" shall mean all of the issued and
outstanding Common Stock, assuming the conversion, exercise or exchange of all
outstanding Common Stock Equivalents.

        "Independent Third Party" shall mean any person other than Orasense,
Isis, Elan or any of their respective Affiliates.

        "Isis Blocking Invention" shall mean [***]

        "Isis Delivery Technology" shall have the meaning given to such term in
the Isis License Agreement.

        "Isis Directors" has the meaning set forth in Clause 7.

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        "Isis Intellectual Property" shall have the meaning set forth in the
Isis License Agreement.

        "Isis License" shall have the meaning set forth in the Isis License
Agreement.

        "Isis License Agreement" shall mean the amended and restated license
agreement between Isis, Orasense and Elan, of even date herewith.

        "Isis Oligonucleotide Drug" shall mean any Oligonucleotide Drug
Controlled by Isis other than the Development Candidate.

        "Know-How" shall mean any and all rights to any discovery, invention
(whether or not patentable), know-how, substances, data, techniques, processes,
systems, formulations and designs which is not generally known to the public.

        "License Agreements" shall mean the Elan License Agreement and the Isis
License Agreement.

        "Licensed Technologies" shall mean together, the Elan Intellectual
Property and the Isis Intellectual Property.

        "Oligonucleotide Drug" shall mean any single stranded [***] at
physiological pH oligonucleotide including those with [***] used as a human
therapeutic and/or prophylactic compound containing between [***] nucleotides
and/or nucleosides including oligonucleotide analogs which may include [***].
For purposes of this agreement, Oligonucleotide Drug shall specifically exclude
oligonucleotides used in [***], oligonucleotides used [***] an oligonucleotide,
oligonucleotides used as [***] or oligonucleotides used as [***].

        "Oral" shall mean administration by way of the mouth for the purpose of
topical or systemic delivery by way of the alimentary canal.

        "Oral Platform" shall mean formulation and excipient systems and
technologies [***] which use [***] to develop dosage forms of drugs and deliver
said dosage forms to the [***] to achieve a local or systemic therapeutic
effect.

        "Orasense Memorandum of Association and Bye-Laws" shall mean the
Memorandum of Association and Bye-Laws of Orasense.

        "Orasense Blocking Invention" shall mean [***]

        "Orasense Collaboration Intellectual Property" shall mean (a) Know-How
Controlled by Orasense through the end of the Research Term, (b) Patents
Controlled by Orasense claiming inventions made on or before the end of the
Research Term, and/or (c) inventions and Patents issued thereon developed by
Orasense, Isis and/or Elan on behalf of Orasense (or any third party under
contract with Orasense, Isis and/or Elan) or otherwise under the Original
Research Plan or the Research Plan. Schedule 1 to this Agreement shall contain,
by way of illustration but not limitation, examples of Orasense Collaboration
Intellectual Property. At the end of the Research Term, the Parties shall amend
Schedule 1 as may be necessary. For the avoidance of doubt, Orasense
Collaboration Intellectual Property does not include any Patents and/or Know-How
Controlled by Elan or Isis, as the case may be.

        "Orasense Intellectual Property" shall mean Orasense Collaboration
Intellectual Property and Orasense Post Collaboration Intellectual Property.

        "Orasense Post-Collaboration Intellectual Property" shall mean
(a) Know-How Controlled by Orasense after the end of the Research Term,
(b) Patents Controlled by Orasense claiming inventions made after the end of the
Research Term, and/or (c) inventions and Patents issued thereon made by Isis on
Orasense's behalf after a Failure to Fund. For the avoidance of doubt, Orasense
Post-Collaboration Intellectual Property does not include any Patents and/or
Know-How Controlled by Elan or Isis, as the case may be.

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        "Original Research Plan" means the Research and Development Program
under the Original Agreement.

        "Participant" means Isis or Elan, as the case may be, and "Participants"
means both of the Participants together.

        "Party" means Elan, Isis, or Orasense, as the case may be, and "Parties"
means all three together.

        "Patents" shall mean any and all patents and patent applications.
Patents shall also include all extensions, continuations, divisionals,
patents-of-additions, re-examinations, re-issues, supplementary protection
certificates and foreign counterparts of such patents and patent applications
and any patents issuing thereon and extensions of any patents licensed
hereunder.

        "Person" means an individual, partnership, corporation, limited
liability company, business trust, joint stock company, trust, unincorporated
association, joint venture, governmental entity or authority or other entity of
whatever nature.

        "Permitted Transferee" means any Affiliate or subsidiary of Elan, EIS or
Isis, to whom this Agreement may be assigned, in whole or in part, pursuant to
the terms hereof or in the case of Elan/EIS, an off-balance sheet special
purpose entity created by Elan or EIS.

        "Product" shall mean any drug under development or developed by or on
behalf of Orasense made or formulated using the Isis Delivery Technology, the
Elan Intellectual Property and/or the Orasense Intellectual Property for
administration to humans.

        "Registration Rights Agreements" means the Registration Rights
Agreements dated April 20, 1999 relating to securities of Isis and Orasense,
respectively.

        "Regulatory Application" shall mean a regulatory application or other
application (including any supplements or amendments thereto) required to be
filed or filed with a Regulatory Authority in a country in connection with the
Commercialization of a pharmaceutical product in such country.

        "Regulatory Approval" means the final approval required to Commercialize
a Product in each country of the Territory, and any other approval which is
required to launch a product in the normal course of business.

        "Research Plan" shall mean the program of development, including a
budget, attached hereto as Schedule 2 which is hereby agreed to by Elan and Isis
as of the Effective Date, with respect to the research, development, and
commercialization of the Oral Platform and the Development Candidate.

        "Research Term" shall mean the period commencing on [***] and continuing
through [***], and any extension thereto by the mutual agreement of Isis and
Elan.

        "Regulatory Authority" shall mean any regulatory authority outside the
United States of America, the approval of which is necessary to market a
Product.

        "Securities Act" means the Securities Act of 1933, as amended.

        "Shares" means the shares of Common Stock of Orasense.

        "Stockholder" means any of EIS, Isis, any Permitted Transferee or any
other Person who subsequently becomes bound by this Agreement as a holder of the
Shares, and "Stockholders" means all of the Stockholders together.

        "Term" shall mean the term of this Agreement.

        "Territory" shall mean all of the countries of the world.

        "Third Party Oligonucleotide Drug" shall mean any Oligonucleotide Drugs
Controlled solely by an Independent Third Party, other than an Isis
Oligonucleotide Drug.

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        "Third Party Product" shall mean Products based upon Third Party
Oligonucleotide Drugs that are made, designed, or otherwise created by or on
behalf of an Independent Third Party after the Effective Date using the Orasense
Collaboration Intellectual Property and/or the Licensed Technologies. For
avoidance of doubt, any Product based upon an Oligonucleotide Drug jointly
developed by an Independent Third Party and Isis other than pursuant to the
Research Plan shall be deemed to be an Isis Product; provided, however, that
such Third Party Product does not incorporate or otherwise utilize Orasense
Collaboration Intellectual Property or Elan Intellectual Property.

        "Transaction Documents" means this Agreement, the Elan License
Agreement, the Isis License Agreement, the Registration Rights Agreements and
associated documentation of even date herewith, by and between Isis, Elan, EIS
and Orasense, as applicable.

        "United States Dollar" and "US$" and "$" means the lawful currency of
the United States of America.

        1.2  In addition, the following definitions have the meanings in the
Clauses corresponding thereto, as set forth below.

Definitions

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  Clause

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"Buyout Option"   20.1 "Closing"   4.2 "Confidential Information"   22.1 "EIS
Director"   7.2 "Elan Valuation"   20.2 "Indemnified Party"   10.6 "Isis
Directors"   7.1 "Isis Valuation"   20.2 "Management Committee"   7.2.1
"Presiding Justice"   20.2 "Purchase Price"   20.2 "R&D Committee"   7.2.2
"Relevant Event"   21.2 "Research Funding"   9.3 "Transfer"   17.1

        1.3  Words importing the singular shall include the plural and vice
versa.

        1.4  Unless the context otherwise requires, reference to a recital,
article, paragraph, provision, clause or schedule is to a recital, article,
paragraph, provision, clause or schedule of or to this Agreement.

        1.5  Reference to a statute or statutory provision includes a reference
to it as from time to time amended, extended or re-enacted.

        1.6  The headings in this Agreement are inserted for convenience only
and do not affect its construction.

        1.7  Unless the context or subject otherwise requires, references to
words in one gender include references to the other genders.

        1.8  Capitalized terms used but not defined herein shall have the
meanings ascribed in the Transaction Documents, if defined therein.

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CLAUSE 2

ORASENSE'S BUSINESS

        2.1  The primary objectives of Orasense is to carry on the business of
the development, testing, registration, Commercialization and licensing of the
Product and the Development Product in the Territory and to achieve the
objectives set out in this Agreement and the License Agreements. The focus of
the collaborative venture will be to develop the Oral Platform and Development
Candidate using the Elan Intellectual Property, the Isis Intellectual Property
and the Orasense Collaboration Intellectual Property to agreed-upon
specifications and timelines and to Commercialize a Product and Development
Product.

        2.2  Except as the Participants otherwise agree in writing and except as
may be provided in this Agreement or the License Agreements, Isis and Orasense
shall exercise their respective powers in relation to Orasense so as to ensure
that the Business is carried on in a proper and prudent manner. Elan shall fully
cooperate with Orasense and Isis in this regard through the end of the Research
Term, and thereafter, at Elan's option and discretion.

        2.3  Each of Isis and Orasense shall use all commercially reasonable and
proper means at its disposal and within its power to maintain, extend and
improve the Business of Orasense, within the limits of this Agreement, and to
further the reputation and interests of Orasense.

        2.4  The central management and control of Orasense shall be exercised
in Bermuda and shall be vested in the Directors and such Persons as they may
delegate the exercise of their powers in accordance with the Orasense Memorandum
of Association and Bye-Laws. The Participants shall use their best endeavors to
ensure that to the extent required pursuant to the laws of Bermuda, and to
ensure the sole residence of Orasense in Bermuda, all meetings of the Directors
are held in Bermuda or other jurisdictions outside the United States and
generally to ensure that Orasense is treated as resident for taxation purposes
in Bermuda.

CLAUSE 3

REPRESENTATIONS AND WARRANTIES

        3.1    Representations and Warranties of Orasense:    Orasense hereby
represents and warrants to each of the Stockholders as follows, as of the
Original Effective Date:

        3.1.1    Organization:    Orasense is an exempted company duly
organized, validly existing and in good standing under the laws of Bermuda, and
has all the requisite corporate power and authority to own and lease its
properties, to carry on its business as presently conducted and as proposed to
be conducted, to execute this Agreement, which has been duly authorized and is
enforceable against Orasense in accordance with its terms, and to carry out the
transactions contemplated hereby.

        3.1.3    Authorization:    The execution, delivery and performance by
Orasense of this Agreement, including the issuance of the Shares, have been duly
authorized by all requisite corporate actions; this Agreement has been duly
executed and delivered by Orasense and is the valid and binding obligation of
Orasense, enforceable against it in accordance with its terms, except as limited
by applicable bankruptcy, insolvency, reorganization, moratorium and other laws
of general application affecting the enforcement of creditors' rights generally,
and by general equity principles and limitations on the availability of
equitable relief, including specific performance. The Shares, when issued as
contemplated hereby, will be validly issued and outstanding, fully paid and
non-assessable and not subject to preemptive or any other similar rights of the
Stockholders or others.

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        3.1.4    No Conflicts:    The execution, delivery and performance by
Orasense of this Agreement, the issuance, sale and delivery of the Shares, and
compliance with the provisions hereof by Orasense, will not:

        (i)    violate any provision of applicable law, statute, rule or
regulation applicable to Orasense or any ruling, writ, injunction, order,
judgment or decree of any court, arbitrator, administrative agency or other
governmental body applicable to Orasense or any of its properties or assets;

        (ii)  conflict with or result in any breach of any of the terms,
conditions or provisions of, or constitute (with notice or lapse of time or
both) a default (or give rise to any right of termination, cancellation or
acceleration) under its charter or organizational documents or any material
contract to which Orasense is a party, except where such violation, conflict or
breach would not, individually or in the aggregate, have a material adverse
effect on Orasense; or

        (iii)  result in the creation of, any Encumbrance upon any of the
properties or assets of Orasense, except as contemplated by the Transaction
Documents.

        3.1.5    Approvals:    As of the date hereof, no permit, authorization,
consent or approval of or by, or any notification of or filing with, any Person
is required in connection with the execution, delivery or performance of this
Agreement by Orasense. Orasense has full authority to conduct its business as
contemplated in the Research Plan and the Transaction Documents.

        3.2    Representations and Warranties of the Stockholders:    Each of
the Stockholders hereby severally represents and warrants to Orasense as of the
Original Effective Date, as follows:

        3.2.1    Organization:    Such Stockholder is a corporation duly
organized and validly existing under the laws of its jurisdiction of
organization and has all the requisite corporate power and authority to own and
lease its respective properties, to carry on its respective business as
presently conducted and as proposed to be conducted and to carry out the
transactions contemplated hereby.

        3.2.2    Authority:    Such Stockholder has full corporate power and
authority to enter into this Agreement and to perform its obligations hereunder,
which have been duly authorized by all requisite corporate action of such
Stockholder. This Agreement is the valid and binding obligation of such
Stockholder, enforceable against it in accordance with its terms, except as
limited by applicable bankruptcy, insolvency, reorganization, moratorium and
other laws of general application affecting the enforcement of creditors' rights
generally, and by general equity principles and limitations on the availability
of equitable relief, including specific performance.

        3.2.3    No Conflicts:    The execution, delivery and performance by
such Stockholder of this Agreement, purchase of the Shares and compliance with
the provisions hereof by such Stockholder will not:

          (i)  violate any provision of applicable law, statute, rule or
regulation known by and applicable to such Stockholder or any ruling, writ,
injunction, order, judgment or decree of any court, arbitrator, administrative
agency or other governmental body applicable to such Stockholder or any of its
properties or assets;

        (ii)  conflict with or result in any breach of any of the terms,
conditions or provisions of, or constitute (with notice or lapse of time or
both) a default (or give rise to any right of termination, cancellation or
acceleration) under the charter or organizational documents of such Stockholder
or any material contract to which such Stockholder is a party, except where such
violation, conflict or breach would not, individually or in the aggregate, have
a material adverse effect on such Stockholder; or

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        (iii)  result in the creation of, any Encumbrance upon any of the
properties or assets of such Stockholder, except as contemplated by the
Transaction Documents.

        3.2.4    Approvals:    As of the date hereof, no material permit,
authorization, consent or approval of or by, or any notification of or filing
with, any Person is required in connection with the execution, delivery or
performance of this Agreement by such Stockholder.

        3.2.5    Investment Representations:    Such Stockholder is capable of
evaluating the merits and risks of its investment in Orasense. Such Stockholder
has not been formed solely for the purpose of making this investment and such
Stockholder is acquiring the Common Stock, if any, for investment for its own
account, not as a nominee or agent, and not with the view to, or for resale in
connection with, any distribution of any part thereof. Such Stockholder
understands that the Shares have not been registered under the Securities Act or
applicable state and foreign securities laws by reason of a specific exemption
from the registration provisions of the Securities Act and applicable state and
foreign securities laws, the availability of which depends upon, among other
things, the bona fide nature of the investment intent and the accuracy of such
Stockholders' representations as expressed herein. Such Stockholder understands
that no public market now exists for any of the Shares and that there is no
assurance that a public market will ever exist for such Shares.

        3.3    Survival:    The representations and warranties in this Clause 3
shall survive for a period of two years from and after the date hereof.

CLAUSE 4

AUTHORIZATION AND CLOSING

        4.1  On the Original Effective Date, Orasense authorized the issuance to
(i) EIS of 2,388 shares of Common Stock and (ii) Isis of 9,612 shares of Common
Stock, issuable as provided in Clause 4.3 hereof

        4.2  On the Original Effective Date, Orasense issued and sold to EIS,
and EIS purchased from Orasense, upon the terms and subject to the conditions
set forth herein, 2,388 shares of Common Stock for an aggregate purchase price
of $2,985,000. Orasense issued and sold to Isis, and Isis purchased from
Orasense, upon the terms and conditions set forth herein, 9,612 shares of Common
Stock for an aggregate purchase price of $12,015,000.

        4.3  [***] The parties agree that they will take all action reasonably
necessary, including amending the Orasense Memorandum of Association and
Bye-Laws to increase the number of shares reserved for issuance by Orasense, to
ensure the issuance of the Stock contemplated by this Section 4.3.

        4.4  A closing shall take place in six month intervals (each, a
"Closing") commencing [***] and will be held at the offices of Isis at 2292
Faraday Avenue, Carlsbad, California 92008 or such other place if any, as the
Parties may agree.

        4.5  At each Closing,

        4.5.1    Orasense shall issue and sell to the Stockholders the
applicable number of shares, calculated pursuant to Section 4.3 above.

        4.5.2  The Parties shall execute and deliver to each other, as
applicable, certificates in respect of the Common Stock described above and any
other certificates, resolutions or documents which the Parties shall reasonably
require.

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        4.6    Exemption from Registration:    

        The Shares will be issued under an exemption or exemptions from
registration under the Securities Act. Accordingly, the certificates evidencing
the Shares shall, upon issuance, contain the following legend:

        THE SECURITIES REPRESENTED HEREBY HAVE NOT BEEN REGISTERED UNDER THE
SECURITIES ACT OF 1933, AS AMENDED, AND MAY NOT UNDER ANY CIRCUMSTANCES BE SOLD,
TRANSFERRED OR OTHERWISE DISPOSED OF WITHOUT AN EFFECTIVE REGISTRATION STATEMENT
FOR SUCH SECURITIES UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND ANY
APPLICABLE STATE SECURITIES LAWS OR AN OPINION OF COUNSEL SATISFACTORY TO THE
COMPANY THAT REGISTRATION IS NOT REQUIRED UNDER SUCH ACT OR APPLICABLE STATE
SECURITIES LAWS.

        THE TRANSFER OF THE SECURITIES REPRESENTED BY THIS CERTIFICATE IS ALSO
SUBJECT TO THE RESTRICTIONS CONTAINED IN THAT CERTAIN AMENDED AND RESTATED
SUBSCRIPTION, JOINT DEVELOPMENT AND OPERATING AGREEMENT, DATED OCTOBER 14, 2002,
BY AND AMONG ELAN CORPORATION, PLC, ELAN INTERNATIONAL SERVICES, INC., ISIS
PHARMACEUTICALS, INC. AND ORASENSE LTD.

CLAUSE 5

DELETED

CLAUSE 6

NON-COMPETITION

        6.1  From the Original Effective Date and through [***], the Parties
agree to be bound by the provisions of Clause 11 of the Elan License Agreement
and the provisions of Clause 11 of the Isis License Agreement, which set forth
the agreement between the parties thereto in relation to the non-competition
obligations of Elan and Isis, respectively.

CLAUSE 7

DIRECTORS; MANAGEMENT AND R&D COMMITTEES

        7.1.    Directors:    

        The Board of Directors of Orasense shall be composed of four Directors.
Prior to an Elan Minority Interest, Isis shall have the right to nominate three
directors of Orasense ("Isis Directors") and EIS shall have the right to
nominate one Director of Orasense ("EIS Director"); provided that one such
director is a resident of Bermuda. Isis may appoint one of the Isis Directors to
be the chairman of Orasense. Each Participant agrees to vote its shares of
Common Stock in favor of the election of the nominees of the other Participant
to the Board of Directors.

        7.1.1  If the chairman is unable to attend any meeting of the Board, the
Isis Directors shall be entitled to appoint another Director to act as chairman
in his place at the meeting.

        7.1.2  If EIS removes the EIS Director, or Isis removes any of the Isis
Directors, EIS or Isis, as the case may be, shall indemnify the other
Stockholder against any claim by such removed Director arising from such
removal.

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        7.1.3  Prior to an Elan Minority Interest, the Directors shall meet not
less than three times in each Financial Year and all Directors' meetings shall
be held in Bermuda to the extent required pursuant to the laws of Bermuda or to
ensure the sole residence of Orasense in Bermuda.

        7.1.4  Prior to an Elan Minority Interest, at any such meeting, the
presence of the EIS Director and one of the Isis Directors shall be required to
constitute a quorum and after an Elan Minority Interest, a majority of the then
acting directors will be required to constitute a quarum. Subject to Clause 18
hereof, the affirmative vote of a majority of the Directors present at a meeting
at which such a quorum is present shall constitute an action of the Directors.
In the event of any meeting being inquorate, the meeting shall be adjourned for
a period of seven days. A notice shall be sent to the EIS Director and the Isis
Directors specifying the date, time and place where such adjourned meeting is to
be held and reconvened.

        7.1.5  In the event of an Elan Minority Interest, each of Isis, and EIS
shall cause the board of Directors of Orasense to be reconfigured so that all of
the Directors are designated by Isis and EIS will lose its right to nominate any
Directors of Orasense.

        7.1.6  In case of an equality of votes at a meeting of the board of
Directors of Orasense, the chairman of Orasense shall not be entitled to a
second or casting vote. In the event of continued deadlock, the board of
Directors shall resolve the deadlock pursuant to the provisions set forth in
Clause 19.

        7.2    Management and R&D Committees:    

        7.2.1  On or about the Original Effective Date, the Directors appointed
a management committee (the "Management Committee") to perform certain
operational functions, such delegation to be consistent with the Directors'
right to delegate powers pursuant to the Orasense Memorandum of Association of
Bye-Laws. As of the Effective Date, the Management Committee consists of four
members, two of whom will be nominated by EIS and two of whom will be nominated
by Isis, and each of whom shall be entitled to one vote. In the event of a
Failure to Fund at any time after the end of the Research Term, EIS will lose
its right to nominate members of the Management Committee and Isis will be able
to nominate all the members of the Management Committee, and each member will be
entitled to one vote. The affirmative vote of at least 3 members of the
Management Committee will constitute an action of the Management Committee.

        7.2.2  On or about the Original Effective Date, the Management Committee
appointed a research and development committee (the "R&D Committee") which is
comprised of four members, two of whom were nominated by Elan and two of whom
were nominated by Isis, and each of whom have one vote. In the event of a
Failure to Fund at any time after the end of the Research Term, EIS will lose
its right to nominate members of R&D Committee and Isis will be able to nominate
all the members of the R&D Committee, and each member will be entitled to one
vote. The affirmative vote of at least 3 members of the R&D Committee will
constitute an action of the R&D Committee.

        7.2.3  The Management Committee's responsibilities include, inter alia,
devising, implementing and reviewing strategy for the business and operations of
Orasense, and in particular, devising Orasense's strategy for research and
development and to monitor and supervise the implementation of Orasense's
strategy for research and development.

        7.2.4  The R&D Committee is responsible for:

        7.2.4.1  establishing a joint Project team consisting of an equal number
of team members from Elan and Isis, including one Project leader from each of
Elan and Isis, except after an Elan Minority Interest the joint project team
will consist of all Isis team members; and

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        7.2.4.2  implementing such portion of the Research Plan that relates to
the Project, as approved by the Management Committee.

        7.2.5  In the event of any dispute amongst the R&D Committee, the R&D
Committee shall refer such dispute to the Management Committee whose decision on
the dispute shall be binding on the R&D Committee. If the Management Committee
cannot resolve the matter, the dispute will be referred to the President of Elan
and the Chief Executive Officer of Isis pursuant to Clause 19 hereof.

        7.2.6  On not more than [***] times in each Financial Year, Elan and
Isis shall permit Orasense or its duly authorized representative on reasonable
notice and at any reasonable time during normal business hours to have access to
inspect and audit the accounts and records of Elan or Isis and any other book,
record, voucher, receipt or invoice relating to the calculation or the cost of
the Research Plan and to the accuracy of the reports which accompanied them. Any
such inspection of Elan's or Isis's records, as the case may be, shall be at the
expense of Orasense, except that if such inspection reveals an overpayment in
the amount paid to Elan or Isis, as the case may be, for the Research Plan
hereunder in any Financial Year of [***] or more of the amount due to Elan or
Isis, as the case may be, then the expense of such inspection shall be borne
solely by Elan or Isis, as the case may be, instead of by Orasense. Any surplus
over the sum properly payable by Orasense to Elan or Isis, as the case may be,
shall be paid promptly by Elan or Isis, as the case may be, to Orasense. If such
inspection reveals a deficit in the amount of the sum properly payable to Elan
or Isis, as the case may be, by Orasense, Orasense shall pay the deficit to Elan
or Isis, as the case may be.

CLAUSE 8

THE RESEARCH PLAN AND REVIEWS

        8.1  The Directors have met and agreed upon the Research Plan, including
the applicable budget. Except for material modifications to the Research Plan,
no additional approval is needed from the Directors to carry out the Research
Plan.

        8.2  The Participants agree that the Management Committee shall submit
to the Directors on February 15th, May 15th, August 15th, and November 15th or
as soon as reasonably practicable thereafter in each Financial Year a report on
the performance of the Business and research and development activities of
Orasense, and the Directors shall hold such meeting as may be necessary to
review the performance of Orasense against the Research Plan for the relevant
year.

CLAUSE 9

RESEARCH AND DEVELOPMENT WORK; FUNDING

        9.1  Orasense will diligently pursue the research, development and
Commercialization of the Elan Intellectual Property, Isis Intellectual Property
and Orasense Intellectual Property. During the Research Term, such work shall be
agreed to and conducted by Elan and/or Isis under contract with Orasense as
provided in the Research Plan. At the end of the Research Term, Isis and Elan
may decide by mutual written agreement to extend the Research Term and adopt a
corresponding Research Plan.

        9.2  During the Research Term, Elan and Isis shall provide reasonable
research and development services as may be reasonably required by Orasense in
accordance with the provisions in the License Agreements. Orasense shall pay
Isis and Elan for any research and development work carried out by each of Isis
and Elan on behalf of Orasense at the end of each month, and any extension
thereto, subject to the proper vouching of research and development work and
expenses. An invoice shall be issued to Orasense by Isis or Elan, as applicable,
by the 15th day of the month following the month in

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which work was performed. The payments by Orasense to Isis or Elan, as the case
may be, shall be at the rates prescribed in the respective License Agreement.
Research and development activities that are outsourced to third party providers
shall be charged to Orasense at fully burdened actual costs.

        9.3  Isis and EIS agree to fund the Research Plan through the end of the
Research Term pursuant to the budget attached to the Research Plan (the
"Research Funding") by contributing cash to Orasense, such funding to be
provided on a pro rata basis in accordance with their respective ownership
interests in Orasense; [***]

        9.4  The Research Funding will be provided by EIS and Isis at such times
as shall be necessary under the Research Plan, as shall be reasonably determined
in good faith by the decision of the Directors.

        9.5  At the end of the Research Term, EIS will have [***] days to notify
Orasense in writing whether EIS wishes to continue funding the Research Plan. If
EIS fails to notify Orasense in writing within such [***]-day period of its
decision to continue funding, then, notwithstanding anything contained herein to
the contrary, EIS will no longer be obligated to fund the Research Plan nor
shall Elan be obligated to provide employees, services or other assistance to
Orasense and a "Failure to Fund" will be deemed to have occurred. In the event
of a Failure to Fund, Isis may continue funding the Research Plan and will
receive Shares as provided in Section 4 of this Agreement.

        9.6  Reference is made to Sections 2.4, 7.2.1, 7.2.2, 10.3, 16.1 and
18.2 of this Agreement and Section 12.5 of the Isis License Agreement with
respect to certain rights that will terminate after a Failure to Fund.

CLAUSE 10

INTELLECTUAL PROPERTY RIGHTS

        10.1 Title and all other ownership rights, including patent rights,
relating to the Orasense Intellectual Property shall belong to Orasense. Title
and all other ownership rights, including patent rights, relating to the Isis
Intellectual Property shall belong to Isis. Title and all other ownership
rights, including patent rights, relating to the Elan Intellectual Property
shall belong to Elan. Otherwise, title and all other ownership rights will
belong to the Party inventing an invention.

        10.2 Prior to a Failure to Fund, the Participants shall discuss in good
faith all material issues relating to filing, prosecution and maintenance of
Patents within the Orasense Intellectual Property insofar as such Patents are of
relevance to the Field and any patentable inventions discovered by Elan, Isis or
Orasense that relate to the Field and any patentable improvements thereto.
Subject to mutual agreement to the contrary by Isis and Elan the following
provisions shall apply:

        10.2.1  Orasense, shall (i) file and prosecute patent applications on
patentable inventions and discoveries within the Orasense Collaboration
Intellectual Property; (ii) defend all such applications against third party
oppositions; and (iii) maintain in force any issued letters patent within the
Orasense Intellectual Property (including any patents that issue on patentable
inventions and discoveries within the Orasense Intellectual Property). Orasense
shall control such filing, prosecution, defense and maintenance.

        10.2.2  Orasense, Elan and Isis shall promptly inform each other in
writing of any alleged infringement of any Patents within the Elan Intellectual
Property, the Isis Intellectual Property or the Orasense Collaboration
Intellectual Property or any alleged misappropriation of trade secrets within
the Elan Intellectual Property, the Isis Intellectual Property or the Orasense
Collaboration Intellectual Property by a third party of which it becomes aware
and provide the Participants and Orasense with any available evidence of such
infringement or misappropriation insofar as such infringements or
misappropriation relate solely to the Field.

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        10.3 Orasense shall have the first right but not the obligation to bring
suit or otherwise take action against any alleged infringement of the Orasense
Intellectual Property or alleged misappropriation of the Orasense Intellectual
Property. If any such alleged infringement or misappropriation occurs that gives
rise to a cause of action both inside and outside the Field, Orasense, in
consultation with the Participants, shall determine the cause of action to be
taken. In the event that Orasense takes such action, Orasense shall do so at its
own cost and expense and all damages and monetary award recovered in or with
respect to such action shall be the property of Orasense. Orasense shall keep
Elan and Isis informed of any action in a timely manner so as to enable Isis and
Elan to provide input in any such action and Orasense shall reasonably take into
consideration any such input. At Orasense's request, the Participants shall
cooperate with any such action at Orasense's cost and expense.

        10.4 In the event that Orasense does not bring suit or otherwise take
action against all infringement of the Orasense Intellectual Property or
misappropriation of the Orasense Intellectual Property, then (i) if only one
Participant determines to pursue such suit or take such action at its own cost
and expense, it shall be entitled to all damages and monetary award recovered in
or with respect to such action and (ii) if the Participants pursue such suit or
action outside of Orasense, they shall negotiate in good faith an appropriate
allocation of costs, expenses and recovery amounts.

        10.5 In the event that a claim is, or proceedings are, brought against
Orasense by a third party alleging that the sale, distribution or use of a
Product in the Territory or use of the Orasense Intellectual Property or the
Isis Intellectual Property, as the case may be, infringes the intellectual
property rights of such party, Orasense shall promptly advise the other
Participants of such threat or suit.

        10.6 Orasense and Isis and any of their respective sublicensees shall
indemnify, defend and hold harmless Elan and its Affiliates, and each of Elan's
and its Affiliates' respective employees, agents, partners, officers and
directors (each an "Indemnified Party") against all actions, losses, claims,
demands, damages, costs and liabilities (including reasonable attorneys fees)
relating directly or indirectly to all such claims or proceedings referred to in
Clause 10.4 above, provided that Elan shall not acknowledge to the third party
or to any other person the validity of any claims of such a third party, and
shall not compromise or settle any claim or proceedings relating thereto without
the prior written consent to Orasense, not to be unreasonably withheld or
delayed. At its option, Elan or Isis, as the case may be, may elect to take over
the conduct of such proceedings from Orasense provided that Orasense's
indemnification obligations shall continue; the costs of defending such claim
shall be borne by Elan or Isis, as the case may be and such Participant shall
not compromise or settle any such claim or proceeding without the prior written
consent of Orasense, such consent not to be unreasonably withheld or delayed.

        10.7 Orasense shall not encumber any of its rights under the Licenses
(except as permitted therein and in Section 12.2 hereof) or the Orasense
Intellectual Property without the prior written consent of Elan and Isis;
provided that after a Failure to Fund, Elan's consent rights with respect to the
Isis License and Orasense Post-Collaboration Property will no longer be
required. Orasense shall not be permitted to assign or sublicense any of its
rights under the Licenses (except as expressly provided under the Elan License
Agreement and Isis License Agreement) or the Orasense Intellectual Property
without the prior written consent of Elan and Isis, respectively, which may be
withheld in Elan's or Isis' sole discretion, as the case may be; provided that
after a Failure to Fund, Elan's consent rights with respect to the Isis License
or Orasense Post-Collaboration Intellectual Property will no longer be required.

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CLAUSE 11

UNBLOCKING LICENSES

        11.1 Isis and its Affiliates shall secure the right to sublicense to
Elan any Isis Blocking Invention made by Isis, Orasense or any of their
respective Affiliates and/or sublicensees or any Independent Third Party under
contract with Isis, Orasense or any of their respective Affiliates and/or
sublicensees. Isis hereby grants to Elan a royalty free, world-wide,
irrevocable, [***] license, including the right to grant sublicenses, to
research, develop, make and have made, offer for sale, sell, import and export
products incorporating the Isis Blocking [***] to practice the Elan Intellectual
Property and/or Orasense Intellectual Property to the extent same could not
otherwise be practiced without first obtaining a license to such Isis Blocking
Invention.

        11.2 Orasense and its Affiliates shall secure the right to sublicense to
Elan any Orasense Blocking Invention made by Isis, Orasense or any of their
respective Affiliates and/or sublicensees or any Independent Third Party under
contract with Isis, Orasense or any of their respective Affiliates and/or
sublicensees. Isis hereby grants to Elan a royalty free, world-wide,
irrevocable, [***] license, including the right to grant sublicenses, to
research, develop, make and have made, offer for sale, sell, import and export
products incorporating the Isis Blocking Inventions [***] to practice the Elan
Intellectual Property and/or Orasense Intellectual Property to the extent same
could not otherwise be practiced without first obtaining a license to such Isis
Blocking Invention.

        11.3 Orasense and Isis and each of their respective Affiliates will
[***] efforts to exclude or, where applicable, minimize royalty or other
compensation obligations in respect of any Isis Blocking Invention and/or
Orasense Blocking Invention, as the case may be. Elan will be responsible for
the payment of such royalty or other compensation obligations triggered by
Elan's practice and use of the Isis Blocking Invention and/or Orasense Isis
Blocking Invention, as the case may be, solely to the extent a royalty or other
compensation obligation to Independent Third Parties are payable with respect to
Elan's use of an Isis Blocking Invention and/or Orasense Blocking Invention, as
the case may be; provided, however, that any royalty or other compensation
obligations payable by Elan to such Independent Third Parties under such license
shall be substantially similar to the royalty obligations or other compensation
obligations payable by Isis and/or Orasense in connection with any license to an
invention or discovery and Patents that may issue thereon that would prevent
Isis and or Orasense from practicing the Elan Intellectual Property and/or the
Orasense Collaboration Intellectual Property licensed to such Independent Third
Party, but for such license.

CLAUSE 12

COMMERCIALIZATION

        12.1 The Participants shall, during the Research Term, assist Orasense
in diligently pursuing the research, development, prosecution and
commercialization of Products in accordance with the Research Plan.

        12.2 During and following the Research Term, Isis as an agent for
Orasense, may negotiate and execute with Independent Third parties regarding a
license and collaboration agreement for developing and Commercializing the
Development Candidate. By executing this Agreement, Elan, and its nominees on
the Board and its nominees on the Management Committee authorize Isis and
Orasense to conduct such negotiation and to execute any agreement that may arise
therefrom.

        12.3 In the event an Independent Third Party shall propose to Orasense
the development of Third Party Products, the Management Committee, by unanimous
decision, shall determine whether or not to develop any such Third Party
Product. Orasense shall be responsible for negotiating with any

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Independent Third Parties commercially reasonable terms (e.g., royalties,
milestones, development fees, manufacturing rights) for developing and licensing
Third Party Products.

CLAUSE 13

MANUFACTURING

        13.1 Isis will notify Elan in writing of Isis' good faith intention to
manufacture or have manufactured an Oligonucleotide Drug incorporating any Elan
Intellectual Property. Elan will have [***] from the receipt of such notice to
notify Isis in writing whether or not Elan wishes to negotiate with Isis
regarding the manufacture of the Oligonucleotide Drug. If Elan fails to respond
to Isis' notice within the [***] or if Elan declines in writing to exercise its
right of first negotiation, then, Isis will be free to manufacture and supply
(either on its own or with a third party) the Oligonucleotide Drug. If Elan
wishes to manufacture the Oligonucleotide Drug incorporating any Elan
Intellectual Property, the parties will negotiate in good faith the terms of a
manufacturing agreement. If despite good faith negotiations, Elan and Isis do
not reach agreement within [***] from Elan's exercise of its right of first
negotiation, then Isis will be free to manufacture and supply (either on its own
or with a third party) the Oligonucleotide Drug.

CLAUSE 14

TECHNICAL SERVICES AND ASSISTANCE

        14.1 Whenever commercially and technically feasible, Orasense shall
contract with Isis or Elan, as the case may be, to perform such other services
as Orasense may require, other than those specifically dealt with hereunder or
in the License Agreements. In determining which Party should provide such
services, the Management Committee shall take into account the respective
infrastructure, capabilities and experience of Elan and Isis.

        14.2 The Parties agree that each Party shall effect and maintain
comprehensive general liability insurance under industry standard insurance
policies in respect of all clinical trials and other activities performed by
them on behalf of Orasense.

        14.3 If Elan or Isis so requires, Isis or Elan, as the case may be,
shall receive, at times and for periods mutually acceptable to the Parties,
employees of the other Party (such employees to be acceptable to the receiving
Party in the matter of qualification and competence) for instruction in respect
of the Elan Intellectual Property or the Isis Intellectual Property, as the case
may be, as necessary to further the Research Plan.

        14.4 The employees received by Elan or Isis, as the case may be, shall
be subject to obligations of confidentiality no less stringent than those set
out in Clause 22 and such employees shall observe the rules, regulations and
systems adopted by the Party receiving the said employees for its own employees
or visitors.

CLAUSE 15

AUDITORS, BANKERS, REGISTERED OFFICE,
ACCOUNTING REFERENCE DATE; SECRETARY; COUNSEL

        Unless otherwise agreed by the Stockholders and save as may be provided
to the contrary herein:

        15.1 the auditors of Orasense shall be Ernst & Young;

        15.2 the bankers of Orasense shall be Bank of Bermuda or such other bank
as may be agreed by the Directors from time to time;

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        15.3 the accounting reference date of Orasense shall be December 31st in
each Financial Year; and

        15.4 the secretary of Orasense shall be Diana Martin or such other
Person as may be appointed by the Directors from time to time.

CLAUSE 16

REGULATORY

        16.1 Orasense shall keep the other Parties promptly and fully advised of
Orasense's regulatory activities, progress and procedures; provided, however,
that Elan's rights hereunder will terminate after a Failure to Fund, except as
is otherwise set forth under the Elan License Agreement. Orasense shall inform
the other Parties of any dealings it shall have with a Regulatory Authority, and
shall furnish the other Parties with copies of all correspondence relating to
the Products. The Parties shall collaborate to obtain any required regulatory
approval of the Regulatory Authority to market the Products.

        16.2 Orasense shall, at its own cost, file, prosecute and maintain any
and all Regulatory Applications for the Products in the Territory in accordance
with the Research Plan.

        16.3 Any and all Regulatory Approvals obtained hereunder for any Product
shall remain the property of Orasense, provided that Orasense shall allow Elan
and Isis access thereto to enable Elan and Isis to fulfill their respective
obligations and exercise their respective rights under this Agreement. Orasense
shall maintain such Regulatory Approvals at its own cost.

        16.4 It is hereby acknowledged that there are inherent uncertainties
involved in the registration of pharmaceutical products with the Regulatory
Authorities insofar as obtaining approval is concerned and such uncertainties
form part of the business risk involved in undertaking the form of commercial
collaboration as set forth in this Agreement. Therefore, except for liabilities
resulting from failure to use reasonable efforts, none of Elan, EIS or Isis
shall have any liability to Orasense solely as a result of any failure of a
Product to achieve the approval of any Regulatory Authority.

CLAUSE 17

TRANSFERS OF SHARES

        17.1    General:    

        No Stockholder shall, directly or indirectly, sell or otherwise transfer
(each, a "Transfer") any Shares held by it except in accordance with this
Agreement. Orasense shall not, and shall not permit any transfer agent or
registrar for any Shares to, transfer upon the books of Orasense any Shares from
any Stockholder to any transferee, in any manner, except in accordance with this
Agreement, and any purported transfer not in compliance with this Agreement
shall be void.

CLAUSE 18

MATTERS REQUIRING PARTICIPANTS' APPROVAL

        18.1 In consideration of Isis and Elan agreeing to enter into the
License Agreements, the Parties hereby agree that Orasense shall not without the
prior approval of the EIS Director and at least two of the Isis Directors:

        18.1.1.  issue any unissued Shares or create or issue any new shares,
except as expressly permitted by the Orasense Bylaws and as contemplated under
this Agreement;

        18.1.2.  alter any rights attaching to any class of share in the capital
of Orasense or alter the Orasense Memorandum of Association and Bye-Laws;

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        18.1.3.  consolidate, sub-divide or convert any of Orasense's share
capital or in any way alter the rights attaching thereto;

        18.1.4.  dispose of Orasense or of any shares in Orasense;

        18.1.5.  do or permit or suffer to be done any act or thing whereby
Orasense may be wound up (whether voluntarily or compulsorily), save as
otherwise expressly provided for in this Agreement;

        18.1.6.  enter into any material contract or transaction except in the
ordinary and proper course of the Business on arm's length terms, or as
contemplated by the Research Plan;

        18.1.7.  alter the number of Directors;

        18.1.8.  change the domicile of Orasense from Bermuda;

        18.1.9.  register any stock of Orasense with any governmental authority
for public trading in any securities market;

        18.1.10.  pay dividends or distributions in respect of, or redeem or
repurchase, the equity of Orasense; or

        18.1.11.  adopt or register or use any trade name, trademark or service
mark on behalf of Orasense.

        18.2 In the event of a Failure to Fund, items 18.1.4, 18.1.6, 18.1.9 and
18.1.10 will be of no further force and effect. In the event of an Elan Minority
Interest, all of the rights under Section 18.1 will be of no further force or
effect.

CLAUSE 19

DISPUTES

        19.1 Should any dispute or difference arise between Elan and Isis, or
between Elan or Isis and Orasense, during the period that this Agreement is in
force, other than a dispute or difference relating to (i) the interpretation of
any provision of this Agreement, (ii) the interpretation or application of law,
or (iii) the ownership of any intellectual property, then any Party may
forthwith give notice to the other Parties that it wishes such dispute or
difference to be referred to the Chief Executive Officer of Isis and the
President of Elan.

        19.2 In any event of a notice being served in accordance with
Clause 19.1, each of the Participants shall within 14 days of the service of
such notice prepare and circulate to the Chief Executive Officer of Isis and the
President of Elan a memorandum or other form of statement setting out its
position on the matter in dispute and its reasons for adopting that position.
Each memorandum or statement shall be considered by the Chief Executive Officer
of Isis and the President of Elan who shall endeavor to resolve the dispute. If
the chief executive officers of the Participants agree upon a resolution or
disposition of the matter, they shall each sign a statement which sets out the
terms of their agreement. The Participants agree that they shall exercise the
voting rights and other powers available to them in relation to Orasense to
procure that the agreed terms are fully and promptly carried into effect.

CLAUSE 20

BUYOUT

        20.1 After Elan's ownership interest in Orasense fall's below [***] Isis
shall have the right to purchase the shares of Orasense Common Stock held by
Elan (the "Buyout Option"), or its Affiliates

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for the stock's then fair market value, as determined by senior officers of Elan
and Isis. Isis will notify Elan in writing of its decision to purchase such
shares.

        20.2 In the event that the Participants do not agree upon a purchase
price for the Shares within [***] Business Days following the receipt by Isis of
written notice from Elan pursuant to Clause 20.1 above, the Participants shall
jointly select a nationally recognized investment banking firm as arbitrator to
make such determination. In the event the Participants do not agree upon the
selection of such investment banking firm, Elan may contact the presiding
justice of the Supreme Court of the State of New York sitting in the City,
County, and State of New York (the "Presiding Justice") and request that an
independent US-based nationally recognized investment banking firm which is
knowledgeable of the pharmaceutical/biotechnology industry be appointed within
10 Business Days. The Presiding Justice shall endeavor to select an investment
banking firm as arbitrator which is technically knowledgeable in the
pharmaceutical/biotechnology industry (and which directly and through its
Affiliates, has no business relationship with, or shareholding in, either of the
Participants). Promptly upon being notified of the arbitrator's appointment, the
Participants shall submit to the arbitrator details of their assessment [***]
together with such information as they think necessary to validate their
assessment. The arbitrator shall notify Isis of the [***] and shall notify Elan
of [***] The Participants shall then be entitled to make further submissions to
the arbitrator within five Business Days explaining why the proposed valuations,
as the case may be, are unjustified. The arbitrator shall thereafter meet with
Isis and Elan and shall thereafter choose either [***] on the basis of [***] The
arbitrator shall use its best efforts to determine the [***] within 30 Business
Days of his appointment. The Participants shall bear the costs of the arbitrator
equally provided that the arbitrator may, in its discretion, allocate all or a
portion of such costs to one Party. Any decision of the arbitrator shall be
final and binding.

        20.3 Isis shall purchase the Shares beneficially owned by Elan by
delivery of the Purchase Price in cash no later than the 15th Business Day
following determination of the Purchase Price by the arbitrator.

        20.4 The Shares so transferred shall be sold by Elan with effect from
the date of such transfer free from any lien, charge or encumbrance, but with
all rights and restrictions attaching thereto.

        20.7 If Isis exercises the Buyout Option, the provisions of Clauses 1,
3, 10.1, 10.3, 10.4, 10.5, 10.6, 11, 19, 20.7, 21, 22, 23 and 24 shall survive
the termination of this Agreement under this Clause 20.7; all other terms and
provisions of this Agreement shall cease to have effect and be null and void.

CLAUSE 21

TERMINATION

        21.1 This Agreement shall govern the operation and existence of Orasense
until (i) terminated by written agreement of all Parties hereto or
(ii) otherwise terminated in accordance with this Clause 21.

        21.2 For the purpose of this Clause 21, a "Relevant Event" is committed
or suffered by a Participant if:

        21.2.1  it commits a material breach of its obligations under this
Agreement or the applicable License, which breach remains uncured [***] after
written notice thereof; provided, however, that (x) if the breaching Participant
has proposed a course of action to rectify the breach and is acting in good
faith to rectify same but has not cured the breach by the [***], such period
shall be extended by such period as is reasonably necessary to permit the breach
to be rectified and (y) if a default involves a good faith dispute regarding the
amount of any required payment, provided any undisputed amount is paid, such
default shall be stayed and the remainder may be withheld for a reasonable
period during which a good faith resolution of the amount owed is being pursued;

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        21.2.2  a distress, execution, sequestration or other process is levied
or enforced upon or sued out against a material part of its property which is
not discharged or challenged within 30 days;

        21.2.3  it is unable to pay its debts in the normal course of business;

        21.2.4  it ceases wholly or substantially to carry on its business,
otherwise than for the purpose of a reconstruction or amalgamation, without the
prior written consent of the other Participant (such consent not to be
unreasonably withheld);

        21.2.5  the appointment of a liquidator, receiver, administrator,
examiner, trustee or similar officer of such Participant or over all or
substantially all of its assets under the law of any applicable jurisdiction,
including without limitation, the United States of America, Bermuda or Ireland;

        21.2.6  an application or petition for bankruptcy, corporate
re-organization, composition, administration, examination, arrangement or any
other procedure similar to any of the foregoing under the law of any applicable
jurisdiction, including without limitation, the United States of America,
Bermuda or Ireland, is filed, and is not discharged within 60 days, or a
Participant applies for or consents to the appointment of a receiver,
administrator, examiner or similar officer of it or of all or a material part of
its assets, rights or revenues or the assets and/or the business of a
Participant are for any reason seized, confiscated or condemned.

        21.3 If either Participant commits a Relevant Event, the other
Stockholder shall have in addition to all other legal and equitable rights and
remedies hereunder, the right to terminate this Agreement upon 30 days' written
notice.

        21.4 In the event of a termination of the Elan License Agreement and/or
the Isis License Agreement, both parties will negotiate in good faith to
determine whether this Agreement should be terminated and if so, which
provisions should survive termination.

        21.5 The provisions of Clauses 1, 3, 10.1, 10.3, 10.4, 10.5, 10.6, 11,
19, 20.7, 21, 22, 23 and 24 shall survive the termination of this Agreement
under Clause 21.3 or by mutual consent pursuant to Clause 21.1 in accordance
with their terms; all other terms and provisions of this Agreement shall cease
to have effect and be null and void upon the termination of this Agreement under
Clause 21.3 or by mutual consent pursuant to Clause 21.1.

CLAUSE 22

CONFIDENTIALITY

        22.1 The Parties acknowledge that it may be necessary, from time to
time, to disclose to each other confidential and proprietary information,
including without limitation, Patents, inventions, works of authorship, trade
secrets, specifications, designs, data, Know-How and other information relating
to the Field, the Products, Elan Intellectual Property, Isis Intellectual
Property and Orasense Intellectual Property, as the case may be, processes,
services and business of the disclosing Party. The foregoing shall be referred
to collectively as "Confidential Information". Any Confidential Information
revealed by a Party to another Party shall be used by the receiving Party
exclusively for the purposes of fulfilling the receiving Party's obligations
under this Agreement and the Development Agreement and for no other purpose.

        22.2 Each Party agrees to disclose Confidential Information of another
Party only to those employees, representatives and agents requiring knowledge
thereof in connection with their duties directly related to the fulfilling of
the Party's obligations under this Agreement. Each Party further agrees to
inform all such employees, representatives and agents of the terms and
provisions of this Agreement and their duties hereunder and to obtain their
consent hereto as a condition of receiving

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Confidential Information. Each Party agrees that it will exercise the same
degree of care, but in no event less than a reasonable degree and protection to
preserve the proprietary and confidential nature of the Confidential Information
disclosed by a Party, as the receiving Party would exercise to preserve its own
proprietary and confidential information. Each Party agrees that it will, upon
request of a Party, return all documents and any copies thereof containing
Confidential Information belonging to or disclosed by, such Party.

        22.3 Notwithstanding the above, each Party may use or disclose
Confidential Information disclosed to it by another party to the extent such use
or disclosure is reasonably necessary in filing or prosecuting patent
applications, prosecuting or defending litigation, complying with patent
applications, complying with applicable governmental regulations or otherwise
submitting information to tax or other governmental authorities, conducting
clinical trials, or making a permitted sub-license or otherwise exercising its
rights hereunder, provided that if a Party is required to make any such
disclosure of the other Party's Confidential Information, other than pursuant to
a confidentiality agreement, such Party shall inform the recipient of the terms
and provisions of this Agreement and their duties hereunder and to obtain their
consent hereto as a condition of receiving Confidential Information.

        22.4 Any breach of this Clause 22 by any of the Persons informed by one
of the Parties is considered a breach by the Party itself.

        22.5 Confidential Information shall not be deemed to include:

        22.5.1  information that is generally available to the public;

        22.5.2  information which is made public by the disclosing Party;

        22.5.3  information which is independently developed by a Party as
evidenced by such Party's written records, without the aid, application or use
of the disclosing Party's Confidential Information;

        22.5.4  information that is published or otherwise becomes part of the
public domain without any disclosure by a Party, or on the part of a Party's
directors, officers, agents, representatives or employees;

        22.5.6  information that becomes available to a Party on a
non-confidential basis, whether directly or indirectly, from a source other than
a Party, which source did not acquire this information on a confidential basis;

        22.5.7  information that becomes available to a Party on a
non-confidential basis, whether directly or indirectly, from a source other than
a Party, which source did not acquire this information on a confidential basis;

        22.5.8  information which the receiving Party is required to disclose
pursuant to;

        22.5.8.1  a valid order of a court or other governmental body or any
political subdivision thereof or otherwise required by law; or

        22.5.8.2  any other requirement of law;

provided that if the receiving Party becomes legally required to disclose any
Confidential Information, the receiving Party shall give the disclosing Party
prompt notice of such fact so that the disclosing Party may obtain a protective
order or other appropriate remedy concerning any such disclosure. The receiving
Party shall fully cooperate with the disclosing Party in connection with the
disclosing Party's efforts to obtain any such order or other remedy. If any such
order or other remedy does not fully preclude disclosure, the receiving Party
shall make such disclosure only to the extent that such disclosure is legally
required;

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        22.5.9  information which was already in the possession of the receiving
Party at the time of receiving such information, as evidenced by its written
records, provided such information was not previously provided to the receiving
Party from a source which was under an obligation to keep such information
confidential; and

        22.5.10  information that is the subject of a written permission to
disclose, without restriction or limitation, by the disclosing Party.

        22.6 The provisions relating to confidentiality in this Clause 22 shall
remain in effect during the term of this Agreement, and for a period of seven
(7) years following the expiration or ea4lrier termination of this Agreement but
shall not apply to any information which a Party is required to file or
otherwise disclose in accordance with requirements which are legally binding on
it.

        22.7 The Parties agree that the obligations of this Clause 22 are
necessary and reasonable in order to protect the Parties' respective businesses,
and each Party expressly agrees that monetary damages would be inadequate to
compensate a Party for any breach by the other Party of its covenants and
agreements set forth herein. Accordingly, the Parties agree and acknowledge that
any such violation or threatened violation will cause irreparable injury to a
Party and that, in addition to any other remedies that may be available, in law
and equity or otherwise, any Party shall be entitled to obtain injunctive relief
against the threatened breach of the provisions of this Clause 22, or a
continuation of any such breach by the other Party, specific performance and
other equitable relief to redress such breach together with its damages and
reasonable counsel fees and expenses to enforce its rights hereunder, without
the necessity of proving actual or express damages.

        22.8 Each of the Parties shall be entitled to provide a copy of this
Agreement (and any subsequent amendments hereto) and the License Agreements to a
potential third party purchaser in connection with the sale of such Party's
business or assets, including without limitation, in the case of Elan, the sale
of the Elan Intellectual Property; provided that the relevant third party
purchaser or assignee has entered into a confidentiality agreement on terms no
less protective than the terms of this Clause 22.

CLAUSE 23

COSTS

        23.1 Each Stockholder shall bear its own legal and other costs incurred
in relation to preparing and concluding this Agreement and the other Transaction
Documents.

        23.2 All other costs, legal fees, registration fees and other expenses
relating to the transactions contemplated hereby, including the costs and
expenses incurred in relation to the incorporation of Orasense, shall be borne
by Orasense.

CLAUSE 24

GENERAL

        24.1    Good Faith:    

        Each of the Parties hereto undertakes with the others to do all things
reasonably within its power that are necessary or desirable to give effect to
the spirit and intent of this Agreement.

        24.2    Further Assurance:    

        At the request of any of the Parties, the other Party or Parties shall
(and shall use reasonable efforts to procure that any other necessary parties
shall) execute and perform all such documents, acts and things as may reasonably
be required subsequent to the signing of this Agreement for assuring to or
vesting in the requesting Party the full benefit of the terms hereof.

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        24.3    Reliance on Representation and Warranties:    

        Each of the Parties hereto hereby acknowledges that in entering into
this Agreement it has not relied on any representation or warranty except as
expressly set forth herein or in any document referred to herein.

        24.4    Force Majeure:    

        Neither Party to this Agreement shall be liable for delay in the
performance of any of its obligations hereunder if such delay is caused by or
results from causes beyond its reasonable control, including without limitation,
acts of God, fires, strikes, acts of war (whether war be declared or not),
insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances or intervention of any relevant government authority, but any such
delay or failure shall be remedied by such Party as soon as practicable.

        24.5    Relationship of the Parties:    

        Nothing contained in this Agreement is intended or is to be construed to
constitute Elan/EIS and Isis as partners, or Elan/EIS as an employee or agent of
Isis, or Isis as an employee or agent of Elan/EIS.

        No Party hereto shall have any express or implied right or authority to
assume or create any obligations on behalf of or in the name of another Party or
to bind another Party to any contract, agreement or undertaking with any third
Party.

        24.6    Counterparts:    

        This Agreement may be executed in any number of counterparts, each of
which when so executed shall be deemed to be an original and all of which when
taken together shall constitute this Agreement.

        24.7    Notices:    

        Any notice to be given under this Agreement shall be sent in writing by
registered or recorded delivery post or reputable overnight courier such as
Federal Express or telecopied to:

If to Orasense at:   Orasense Ltd.
c/o Isis Pharmaceuticals, Inc.
2292 Faraday Avenue
Carlsbad, California 92008     Attention:   Ms. Lynne Parshall     Telephone:  
(760) 603-2460     Telefax:   (760) 931-9639
If to Isis to:
 
Isis Pharmaceuticals, Inc.
2292 Faraday Avenue
Carlsbad, California 92008     Attention:   Ms Lynne Parshall     Telephone:  
(760) 603-2460     Telefax:   (760) 931-9639
with a copy to:
 
Isis Pharmaceuticals, Inc.
2292 Faraday Avenue
Carlsbad, CA 92008     Attention:   Grantland E. Bryce     Telephone:  
760-603-2707     Fax:   760-268-4922

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If to Elan at:
 
Elan Corporation, plc
C/o Elan International Services, Ltd.
102 St. James Court
Flatts,
Smiths FL04
Bermuda     Attention:   Secretary     Telephone:   441 292 9169     Fax:   441
292 2224

        with a copy to each of Isis, EIS and their respective counsel at the
addresses indicated above;

        or to such other address(es) as may from time to time be notified by any
Party to the others hereunder.

        Any notice sent by mail shall be deemed to have been delivered within
three Business Days after dispatch or delivery to the relevant courier and any
notice sent by telecopy shall be deemed to have been delivered upon confirmation
of receipt by telephone. Notices of change of address shall be effective upon
receipt.

        24.8    Governing Law    

        This Agreement shall be governed by and construed in accordance with the
laws of the State of New York without giving effect to any choice or conflict or
law provision or rule.

        24.9    Arbitration    

        (a)  Any dispute under this Agreement or the other Transaction Documents
which is not settled by mutual consent (whether pursuant to the provisions in
Clause 19 hereof or otherwise) shall be finally settled by binding arbitration,
conducted in accordance with the Commercial Arbitration Rules of the American
Arbitration Association by one (1) arbitrator appointed in accordance with said
rules. Such arbitrator shall be reasonably satisfactory to each of the Parties;
provided, that if the Parties are unable to agree upon the identity of such
arbitrator within 15 days of demand by either Party, then either Party shall
have the right to petition the Presiding Justice to appoint an arbitrator.

        The arbitration shall be held in New York, New York and the arbitrator
shall be an independent expert in pharmaceutical product development and
marketing (including clinical development and regulatory affairs).

        (b)  The arbitrator shall determine what discovery will be permitted,
consistent with the goal of limiting the cost and time which the Parties must
expend for discovery; provided the arbitrator shall permit such discovery as
they deem necessary to permit an equitable resolution of the dispute.

        Any written evidence originally in a language other than English shall
be submitted in English translation accompanied by the original or a true copy
thereof.

        The costs of the arbitration, including administrative and arbitrators'
fees, shall be shared equally by the Parties and each Party shall bear its own
costs and attorneys' and witness' fees incurred in connection with the
arbitration.

        (c)  In rendering judgment, the arbitrator shall be instructed by the
Parties that he shall be permitted to select solely from between the proposals
for resolution of the relevant issue presented by each Party, and not any other
proposal.

        A disputed performance or suspended performances pending the resolution
of the arbitration must be completed within thirty (30) days following the final
decision of the arbitrators or such other reasonable period as the arbitrators
determine in a written opinion.

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        (d)  Any arbitration under the Transaction Documents shall be completed
within one year from the filing of notice of a request for such arbitration.

        The arbitration proceedings and the decision shall not be made public
without the joint consent of the Parties and each Party shall maintain the
confidentiality of such proceedings and decision unless otherwise permitted by
the other Party.

        (e)  The Parties agree that the decision shall be the sole, exclusive
and binding remedy between them regarding any and all disputes, controversies,
claims and counterclaims presented to the arbitrators. Application may be made
to any court having jurisdiction over the Party (or its assets) against whom the
decision is rendered for a judicial recognition of the decision and an order of
enforcement.

        24.10    Severability:    

        If any provision in this Agreement is agreed by the Parties to be,
deemed to be or becomes invalid, illegal, void or unenforceable under any law
that is applicable hereto, such provision will be deemed amended to conform to
applicable laws so as to be valid and enforceable or, if it cannot be so amended
without materially altering the intention of the Parties, it will be deleted,
with effect from the date of such agreement or such ea4lrier date as the Parties
may agree, and the validity, legality and enforceability of the remaining
provisions of this Agreement shall not be impaired or affected in any way.

        24.11    Amendments:    

        No amendment, modification or addition hereto shall be effective or
binding on any Party unless set forth in writing and executed by a duly
authorized representative of all Parties.

        24.12    Waiver:    

        No waiver of any right under this Agreement shall be deemed effective
unless contained in a written document signed by the Party charged with such
waiver, and no waiver of any breach or failure to perform shall be deemed to be
a waiver of any future breach or failure to perform or of any other right
arising under this Agreement.

        24.13    Assignment:    

        None of the Parties shall be permitted to assign its rights or
obligations hereunder without the prior written consent of the other Parties
except as follows:

        24.13.1  Elan, EIS and/or Isis shall have the right to assign their
rights and obligations hereunder to their Affiliates provided, however, that
such assignment does not result in adverse tax consequences for any other
Parties.

        24.13.2  Elan and EIS shall have the right to assign their rights and
obligations hereunder to an off-balance sheet special purpose entity established
by Elan or EIS.

        24.13.3  Elan, EIS and/or Isis shall have the right to assign or
otherwise transfer their rights and obligations hereunder in connection with a
sale of all or substantially all of the business of such Party to which the
transaction Documents relate, whether by merger, sale of stock, sale of assets
or otherwise; provided however, that Elan or EIS may not assign or otherwise
transfer (including by merger, sale of stock or sale of assets) its rights to
fund Orasense or extend the Research Term.

        24.14    Whole Agreement/No Effect on Other Agreements:    

        This Agreement (including the Schedules attached hereto) and the other
Transaction Documents set forth all of the agreements and understandings between
the Parties with respect to the subject

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matter hereof, and supersedes and terminates all prior agreements and
understandings between the Parties with respect to the subject matter hereof.
There are no agreements or understandings with respect to the subject matter
hereof, either oral or written, between the Parties other than as set forth in
this Agreement and the other Transaction Documents.

        In the event of any ambiguity or conflict arising between the terms of
this Agreement and those of the Orasense Memorandum of Association and Bye-Laws,
the terms of this Agreement shall prevail.

        No provision of this Agreement shall be construed so as to negate,
modify or affect in any way the provisions of any other agreement between any of
the Parties unless specifically referred to, and solely to the extent provided
herein. In the event of a conflict between the provisions of this Agreement and
the provisions of the License Agreements, the terms of the License Agreements
shall prevail.

        24.16    Successors:    This Agreement shall be binding upon and inure
to the benefit of the Parties hereto, their successors and permitted assigns.

[Signature Page Follows]

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        IN WITNESS WHEREOF, the Parties hereto have executed this Agreement on
the day first set forth above.

 
 
 
SIGNED
 
 
 
BY:
/s/  KEVIN INSLEY      

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for and on behalf of
ELAN CORPORATION, PLC
in the presence of:
/s/  DEBBIE BURYJ      

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SIGNED
 
 
 
BY:
/s/  DEBBIE BURYJ      

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for and on behalf of
ELAN INTERNATIONAL SERVICES, LTD.
in the presence of:
/s/  KEVIN INSLEY      

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SIGNED
 
 
 
BY:
/s/  B. LYNNE PARSHALL      

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for and on behalf of
ISIS PHARMACEUTICALS, INC.
in the presence of:
/s/  GRANTLAND E. BRYCE      

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SIGNED
 
 
 
BY:
/s/  E.C.J      

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for and on behalf of
ORASENSE LTD.
in the presence of:
/s/  ILLEGIBLE      

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SCHEDULE 1

ORASENSE COLLABORATION INTELLECTUAL PROPERTY

        [***]

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SCHEDULE 2

RESEARCH PLAN(1)

        [***]

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(1)Promptly following the Effective Date, the Management Committee shall clarify
the Research Plan as necessary to further detail the objectives of Orasense
through the end of the Research Term.

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Table 1. 2002 Oral Clinical Studies

        [***]

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BUDGET

        [***]

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ORASENSE BUDGET ASSUMPTIONS

        [***]

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QuickLinks

AMENDED AND RESTATED SUBSCRIPTION, JOINT DEVELOPMENT AND OPERATING AGREEMENT
ELAN CORPORATION, PLC ELAN INTERNATIONAL SERVICES, LTD. ISIS PHARMACEUTICALS,
INC. AND ORASENSE LTD. October 24, 2002