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Exhibit 4.3  

 
 

2nd Swing, Inc.
  SUBSCRIPTION AGREEMENT
  AND
  LETTER OF INVESTMENT INTENT    
  

2nd
Swing, Inc.

16305 36th Avenue North

Suite 550

Plymouth, Minnesota 55446 

Gentlemen:

        The
undersigned, intending to be legally bound, hereby irrevocably subscribes for and offers and agrees to purchase 160,000 shares of common stock, $.01 par value per share (the
"Common Shares"), of 2nd Swing, Inc., a Minnesota corporation (the "Company"), at a
purchase price of $1.50 per Common Share. 

        The
holder of the Common Shares being issued shall have rights as follows: 

	1.
	If
the Company at any time divides the outstanding Common Shares into a greater number of shares (whether pursuant to a stock split, stock dividend, or otherwise), and conversely, if
the outstanding
Common Shares are combined into a smaller number of shares, the Common Shares owned by the undersigned, or the then holder, shall be proportionately adjusted to reflect the reduction or increase in
the value of each such share;

	2.
	If
any capital reorganization or reclassification of the Common Shares of the Company, or consolidation or merger of the Company with another corporation, or the sale of all or
substantially all of the Company's assets to another corporation shall be effected in such a way that the holders of the Company's Common Shares shall be entitled to receive stock, securities, or
assets with respect to or in exchange for such shares, then, as a condition of such reorganization, reclassification, consolidation, merger or sale, where the price of the Common Shares is less than
$1.50 per share, or in the event the Company issues shares to a third party at a price of less than $1.50 per share, the undersigned, or the then holder, shall be issued additional Common Shares,
without cost or other consideration, so that the additional shares, together with the shares already registered to the undersigned, or the then holder, will have a total valuation of $240,000. The
calculation required herein shall be made by the then Company auditor whose decision shall be conclusive, final and binding upon the undersigned, or the then holder, and the Company.

	3.
	If
the Company takes any other action, or if any other event occurs, which does not come within the scope of the above provisions (1) and (2), but which would result in a
dilution of the undersigned's or the then holder's Common Shares being acquired hereunder, an appropriate adjustment in the number of shares shall be made by the Company to the undersigned, or the
then holder, without additional cost or other consideration to the undersigned, or the then holder, so that the total value of shares being acquired hereunder plus any additional shares issued is
$240,000.

	4.
	In
the event the Company elects to register shares for secondary trading ("Registration"), and subject to applicable state and federal
securities laws and regulations issued by the Securities and Exchange Commission, the Company will allow the holders of the Common Shares, pro rata by and among them, to join with the Company to sell
those number of Common Shares owned by such holders as permitted to be included as part of such Registration ("Piggyback Registration"). The Company
will pay all costs and expenses incident to the Piggyback Registration, including the 

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reasonable
fees and expenses of Company and selling shareholder's counsel, the reasonable fees and expenses of Company accountants, and other costs and expenses incident to the preparation, printing
and filing under the applicable securities laws of any such Registration, including the costs incurred in connection with the qualification of securities under the laws of various jurisdictions. The
Company will not pay any underwriting commissions or discounts being charged to the holders of Common Shares participating in the Piggyback Registration, which commissions or discounts shall be paid
by such holders on a per share basis as to the number of shares sold. 

	5.
	Each
party (the "Indemnifying Party") will indemnify, defend, and hold the other harmless (the "Indemnified
Party") against any loss, claim, damage or liability to which the Indemnified Party may be subject insofar as such losses, claims, damages, or liabilities are caused by any
untrue or alleged untrue statement of any material fact contained in any registration statement, prospectus, or amendment to either such instrument, or arise out of or are based upon the omission or
the alleged omission to state
a material fact required to be stated by the Indemnifying Party participating in the Piggyback Registration. For purposes of this paragraph 5, reference to the parties shall mean the Company,
and the Company's directors, officers, agents, and representatives signing any registration statement, and reference to the undersigned or the then holder shall mean and refer to such undersigned or
the then holder and his respective personal representatives, heirs, permitted successors or permitted assigns. The Indemnified Party shall give prompt notice to the Indemnifying Party of any claim it
receives. No resolution of a claim is required if the Indemnifying Party or Indemnified Party is required to admit a violation of law or regulation of a governmental authority or political subdivision
thereof. 

        The
undersigned, to induce the Company to accept this offer, acknowledges, warrants and represents to the Company as follows: 

	1.
	The
undersigned has received, carefully reviewed, and is familiar with any Company information requested and/or reviewed and has relied only on the information contained therein and
the information provided pursuant to paragraph 11 in reaching his investment decision. The undersigned further understands and acknowledges that no person has been authorized to give any
information or to make any representations which were not contained in any Company information requested and/or reviewed or furnished pursuant to paragraph 11 and that he has received no oral
representations, warranties or information regarding the Company or the prospective investment in the Common Shares from the officers, directors or other representatives of the Company.

	2.
	The
undersigned has obtained, to the extent deemed necessary, his own personal professional advice with respect to (i) the risks inherent in an investment in the Common Shares;
(ii) the suitability of the investment in light of the financial condition and investment needs of the undersigned; and (iii) legal, tax and accounting matters.

	3.
	The
undersigned acknowledges that he, either alone or with the assistance of any purchaser representative(s) with whom he has consulted, has sufficient knowledge, skill and experience
in financial and business matters to be capable of evaluating the merits and risks of the undersigned's prospective investment in the Common Shares and to make an informed investment decision.

	4.
	The
undersigned recognizes (i) that an investment in the Common Shares involves a high degree of risk, and that such risks may result in the loss of the total amount of his
investment; (ii) that the purchase of the Common Shares is a long-term investment; (iii) that transferability and sale of the Common Shares is restricted in many ways;
(iv) that the Company makes no representations whatsoever concerning the present or prospective value of the Common Shares; and (v) that in the event of disposition of the Common Shares,
the undersigned could sustain a total loss of his investment. 

2

 
	5.
	The
undersigned understands that the Company has a limited financial and operating history and limited earnings, that there is not presently any trading market for the Common Shares
and none is likely to develop, and that there is no assurance that the Company will be successful.

	6.
	The
undersigned is of legal age and is a bona fide resident of the state set forth on the signature page hereof.

	7.
	The
undersigned intends to acquire and hold the Common Shares for his own account as principal, for investment purposes only, and not with a view to, or for resale in connection with,
the distribution thereof within the meaning of the Securities Act of 1933, as amended (the "Act"). By such representation the undersigned also means
that it is his intention to receive and hold the Common Shares for his own account and not directly or indirectly on behalf of, or as nominee for, any other person or entity. The undersigned has no
contract, undertaking, understanding, agreement or arrangement with any person or entity to sell or transfer to any such person or entity or to have any such person or entity sell all or any part of
the Common Shares to which he is hereby subscribing, and is not aware of any occurrence, event, or circumstance upon the happening of which he intends to transfer or sell the Common Shares or any part
thereof; and the undersigned does not have any present intention to sell or transfer all or any part of the Common Shares after a lapse of any particular period of time.

	8.
	The
undersigned acknowledges that the availability of the exemptions from the registration provisions of the Act and applicable state securities laws pursuant to which the Company is
offering and selling the Common Shares are dependent upon the undersigned's investment intentions and that the Company will rely on the representations made herein as a basis for exemption from
registration. Accordingly, the undersigned acknowledges that the Common Shares acquired by the undersigned may not be sold, assigned or otherwise transferred (i) except pursuant to an effective
registration statement under the Act and applicable state securities laws (it being expressly understood that the Company does not intend, nor is it obligated now or at any future date, to register
the Common Shares under the Act or any state securities laws) or (ii) unless the undersigned supplies the Company with an opinion of an attorney of the undersigned's choosing (which opinion
shall be addressed, and satisfactory in form and substance, to the Company and its counsel, and which attorney shall also be satisfactory to the Company and its counsel) to the effect that the
proposed sale, assignment or other transfer is exempt from registration under applicable federal and state securities laws. As a result thereof, the undersigned may be required to hold the Common
Shares for an indefinite period of time. Further, the undersigned acknowledges that it is the position of the United States Securities and Exchange Commission (the
"SEC") and many state securities commissioners that the basis for the exemptions from registration upon which the Company is relying would not be
present if the representations made by the undersigned herein merely mean that the present intention of the undersigned is to hold the Common Shares with an intent to resell in the event of any
foreseeable specific contingency or in connection with a contemplated liquidation or settlement of any loan obtained for the acquisition of the Common Shares and for which the Common Shares are
pledged as security.

	9.
	The
undersigned acknowledges that a stop transfer order or other appropriate notation will be entered on the Company's stock transfer books with respect to the Common Shares and that
any certificate to be issued representing the Common Shares will contain substantially the following legend: 

THE
SECURITIES EVIDENCED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933 OR APPLICABLE STATE SECURITIES LAWS, AND MAY NOT BE SOLD, TRANSFERRED, ASSIGNED, OFFERED, PLEDGED OR OTHERWISE
DISTRIBUTED FOR VALUE EXCEPT PURSUANT TO AN EFFECTIVE REGISTRATION STATEMENT UNDER SUCH ACT AND SUCH LAWS COVERING SUCH SECURITIES OR 

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THE COMPANY RECEIVES AN OPINION OF COUNSEL ACCEPTABLE TO THE COMPANY STATING THAT SUCH SALE, TRANSFER, ASSIGNMENT, PLEDGE OR DISTRIBUTION IS EXEMPT FROM THE REGISTRATION REQUIREMENTS OF SUCH ACT AND
SUCH LAWS. 

	10.
	The
undersigned has been advised that although the Common Shares will constitute "restricted securities," as that term is defined in
Rule 144 promulgated under the Act, Rule 144 is not currently available nor contemplated to become available within the near future for resale of the Common Shares by
"affiliates" of the Company, as that term is defined in Rule 144 or, with respect to non-affiliates of the Company, where the Common
Shares have not been fully paid for and beneficially owned for a period of at least two years; and the undersigned further acknowledges that the Company is not currently obligated to make the filings
and reports, or make the information publicly available, that is a condition to the availability of Rule 144. The undersigned acknowledges and understands that even if Rule 144 is
available for the resale of the Common Shares there is not likely to be any market for such securities, and finding a purchaser would be difficult.

	11.
	The
undersigned acknowledges that he has been afforded an opportunity to examine all books, records, agreements and other documents relevant to the Company and this investment and has
been given an opportunity to ask questions and receive answers from duly designated representatives of the Company concerning the Company, the Common Shares and any other matters relevant and material
to an investment in the Common Shares, and has utilized such opportunity to his satisfaction to verify the accuracy and completeness of the information and to obtain any other relevant information
which he may have sought. The undersigned is fully satisfied with the responses to such questions as he has asked and such requests for additional information as he has made.

	12.
	The
undersigned acknowledges and understands the meaning and legal consequences of the representations, warranties and covenants set forth herein and that the Company has relied or
will rely upon such representations, warranties and covenants; and the undersigned hereby agrees to indemnify and hold the Company and its officers, directors, controlling persons, agents and
employees harmless from and against any and all loss, claim, damage, liability or expense, and any action in respect thereof, joint or several, arising out of a breach of any such representation,
warranty or covenant, together with all reasonable costs and expenses (including attorneys' fees) incurred by the Company or any such person in connection with any action, suit, proceeding, demand,
assessment or judgment incident to any of the matters so indemnified against. Notwithstanding the foregoing, however, no representation,
warranty, acknowledgment or agreement made herein by the undersigned shall in any manner be deemed to constitute a waiver of any rights granted to him under federal or state securities laws.

	13.
	The
undersigned acknowledges and understands that in order to claim the exemptions from the registration requirements of the federal and state securities laws and regulations, the
Company will rely on the undersigned's representations contained herein for the purpose of determining whether he it qualifies as an Accredited Investor (as that term is defined in Rule 501(a)
of Regulation D under the Act). By initialing one or more of the lettered subparagraphs below, the undersigned, for 

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the
purpose of inducing a sale of Common Shares by the Company to the undersigned, hereby represents that the statement or statements initialed below are true and correct. 

	X	 	A.	 	The undersigned certifies that he or she had an individual income (i.e. not including the income of the investor's spouse) in excess of $200,000 in each of the two most recent years or joint income with his or her spouse
in excess of $300,000 in each of those years and reasonably expects to reach the same income level in the current year. NOTE: This provision applies only to natural persons.
	X	 	B.	 	The undersigned certified that as of the date of this Agreement, the undersigned (either individually or jointly with his or her spouse) has a net worth in excess of $1,000,000 (for purposes hereof "net worth" includes the value of the investor's home, home furnishings and automobiles). NOTE: This provision applies only to natural persons.
	  	 	C.	 	The undersigned certifies that it is a trust, not formed for the specific purpose of acquiring the securities offered by the Company, with total assets in excess of $5,000,000 and whose purchase is directed by a
sophisticated person or persons who have such knowledge and experience in financial and business matters that they are capable of evaluating the merits and risks of the prospective investment.
	  	 	D.	 	None of the foregoing statements is true with respect to the undersigned.

	14.
	The
undersigned understands and agrees that, although the Company will use its best efforts to keep the information provided to the Company with respect to the status of the
undersigned as an accredited investor strictly confidential, the Company may present this Agreement and the information provided in it to such parties as it deems advisable if called upon to establish
the availability under any federal or state securities laws of an exemption from registration for the offer and sale of the Common Shares or if the contents hereof are relevant to any issue in any
action, suit or proceeding to which the Company is a party.

	15.
	This
Agreement shall be binding upon and shall inure to the benefit of the parties hereto and to the successors and assigns of the Company and to the personal representatives, heirs,
guardians, executors, administrators, legal representatives and successors of the undersigned.

	16.
	The
undersigned represents and warrants to the Company that (i) the information contained herein is complete and accurate as of the date set forth at the end hereof and may be
relied upon by the Company and (ii) the undersigned will notify the Company immediately of any material change in any of such information occurring prior to the Company's acceptance of this
subscription.

	17.
	This
Agreement shall be governed by and construed in accordance with the laws of the State of Minnesota.

	18.
	In
the event that any provision hereof is invalid or unenforceable under any applicable statute or rule of law, then such provision shall be deemed inoperative to the extent that it
may conflict therewith and shall be deemed modified to conform with such statute or rule of law. Any provision hereof which may prove invalid or unenforceable under any law shall not affect the
validity or enforceability of any other provision hereof.

	19.
	This
Agreement constitutes the entire agreement among the parties hereto with respect to the subject matter hereof; and neither this Agreement nor any provisions hereof shall be
waived, modified, discharged or terminated except by an instrument in writing signed by the party against whom any waiver, modification, discharge or termination is sought.

	20.
	The
undersigned agrees that this Agreement and the undersigned's interest herein may not be transferred or assigned. 

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	21.
	The
representations, warranties and agreements of the undersigned contained herein, including the undersigned's agreement to indemnify, shall survive, and remain in full force and
effect, after the execution hereof and the acceptance of this Agreement by the Company and the payment for the Common Shares. 

        NOTE:
The Company reserves the right to request additional representations, information and/or documentation before accepting this subscription. 

        IN
WITNESS WHEREOF, the undersigned has executed this Subscription Agreement and Letter of Investment Intent on the 2nd day of October, 2000. 

	/s/  STANLEY A. BODINE      
 Subscriber's Signature	 	 
	

Stanley A. Bodine
 Subscriber's Name	
 	

 
	

2735 Dean Parkway
 Residence Address	
 	

 
	

Minneapolis, MN 55416
 City, State and ZIP Code	
 	

 
	

 Social Security Number or

Tax Identification Number	
 	

 

 
 

ACCEPTANCE:    
  

        2nd Swing, Inc. hereby accepts this subscription and, in consideration of all of the acknowledgments, warranties and representations
contained herein, agrees to issue the Common Shares. 

Dated:
October    , 2000 

	 	 	2nd Swing, Inc.
	

 	
 	

By	
 	

 
	 	 	 	 	/s/  DAVID R. POMIJE      
 David R. Pomije

Its Chairman of the Board

Addendum  

        The undersigned agrees that upon completion by the Company of a registered public offering of its Common Shares, the antidilution rights provided in
paragraphs 2 and 3 on page 1 of this Agreement shall be terminated. 

	 	 	/s/  STANLEY A. BODINE      
 Stanley A. Bodine

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Exhibit 10.1  

CONFIDENTIAL TREATMENT REQUESTED

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

Isis License Agreement

Execution Copy (V7)

24 October 2002  

 
 

AMENDED AND RESTATED
  LICENSE AGREEMENT    
    
    
    BY AND BETWEEN    
    
    
    ORASENSE LTD    
    
    A Bermuda Limited Company    
    
    
    ISIS PHARMACEUTICALS,
 INC    
    
    A Delaware Corporation    
    
    
    AND    
    
    
    ELAN CORPORATION, PLC    
    
    A Public Irish Company    
    
    
    October 24, 2002    

   TABLE OF CONTENTS  

	CLAUSE
	 	HEADING
	 	PAGE

	1	 	DEFINITIONS; INTERPRETATION	 	3
	

2	
 	

GRANT OF RIGHTS	
 	

7
	

3	
 	

INTENTIONALLY DELETED	
 	

8
	

4	
 	

DEVELOPMENT OF PRODUCT	
 	

8
	

5	
 	

REGULATORY APPROVALS	
 	

8
	

6	
 	

FINANCIAL PROVISIONS	
 	

9
	

7	
 	

CONFIDENTIAL INFORMATION	
 	

10
	

8	
 	

WARRANTIES AND INDEMNITIES	
 	

12
	

9	
 	

INTELLECTUAL PROPERTY OWNERSHIP RIGHTS	
 	

14
	

10	
 	

RIGHTS EXPLOITATION OUTSIDE THE FIELD	
 	

15
	

11	
 	

NON-COMPETITION	
 	

16
	

12	
 	

TERM AND TERMINATION OF AGREEMENT	
 	

16
	

13	
 	

FORCE MAJEURE	
 	

18
	

14	
 	

SETTLEMENT OF DISPUTES; GOVERNING LAW	
 	

18
	

15	
 	

ASSIGNMENT	
 	

18
	

16	
 	

NOTICES	
 	

19
	

17	
 	

MISCELLANEOUS CLAUSES	
 	

19

2

   
        AMENDED AND RESTATED LICENSE AGREEMENT made this 24th day of October, 2002 among, Isis Pharmaceuticals, Inc., a
Delaware corporation, Elan Corporation, plc, Orasense Ltd. a Bermuda limited company. 

RECITALS:  

        A.    Contemporaneously
herewith, Elan, EIS, Orasense and Isis (capitalized terms used herein are defined below) are entering into the Development Agreement for the purpose of
amending, restating and recording the terms and conditions of a joint venture and of regulating their relationship with each other and certain aspects of the affairs of and their dealings with
Orasense. 

        B.    Isis
is beneficially entitled to the use of certain know-how and certain patents that have been granted or are pending in relation to the development and
production of various drug delivery technologies and drug products. 

        C.    Orasense
desires to enter into this Agreement with Isis so as to permit Orasense to utilize the Isis Intellectual Property in the research, development, manufacture,
distribution and sale of Products in the Field and in the Territory. 

        D.    Orasense
and Isis entered into that certain License Agreement (the "Original License Agreement") dated April 20, 1999 (the "Original Effective Date"). The Parties
now wish to amend, restate and supercede the Original License Agreement with this Agreement. 

        NOW THEREFORE, IT IS HEREBY AGREED AS FOLLOWS: 

	1.
	DEFINITIONS; INTERPRETATION

        A.    Definitions.    In this Agreement, the following definitions shall apply: 

        1.1.  "Affiliate"
shall mean, with respect to Elan or Isis, any corporation or entity other than Orasense (and entities controlled by it) controlling, controlled or under the
common control of Elan or Isis, 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. 

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

        1.3.  "cGCP",
"cGLP" and "cGMP" shall mean current Good Clinical Practices, current Good Laboratory Practices and current Good Manufacturing Practices respectively; 

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

        1.5.  "Control"
shall mean the ability of a Party 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 such Party and a third party; 

        1.6.  "Cost
of Living Increase" shall mean, with respect to any year of the Term, any increase in the Consumer Price Index published by the Bureau of Labor Statistics of the
United States Department of Labor, All Urban Consumers, United States City Average, All Items (1982-84=100); 

        1.7.  "Development
Agreement" shall mean the Amended and Restated Joint Development and Operating Agreement of even date entered into among Isis, Elan, EIS and Orasense; 

3

 

        1.8.  "Development
Candidate" shall mean ISIS 104838 [***] of TNF-a, as more specifically detailed
in Exhibit A hereto; 

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

        1.10.  "Effective
Date" shall mean the date of execution and delivery of this Agreement; 

        1.11.  "EIS"
shall mean Elan International Services, Ltd., a Bermuda limited company; 

        1.12.  "Elan"
shall mean Elan Corporation, plc, a public limited company incorporated under the laws of Ireland, its, successors and permitted assigns; 

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

        1.14.  "Elan
JV" shall mean an entity that Elan and a third party (i) establish or have established; (ii) take shareholdings in or have a right to
take shareholdings in; and (iii) grant certain licenses in and to certain intellectual property rights for the purpose of implementing a strategic alliance; 

        1.15.  "Elan
License" shall have the meaning set forth in Clause 2.1 of the Elan License Agreement; 

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

        1.17.  "Excluded
Isis Technology" shall mean any Isis oligonucleotide chemistry technology including, without limitation, modified heterocycles, sugars or
backbone linkages or conjugation technology; 

        1.18.  "Failure
to Fund" shall have the meaning set forth under Clause 9 of the Development Agreement; 

        1.19.  "FDA"
shall mean the United States Food and Drug Administration or any successors or agency the approval of which is necessary to market a product in the
United States of America; 

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

        1.21.  "Full
Time Equivalent Rate" shall mean, for the services proposed to be rendered by Isis [***]; 

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

        1.23.  "Isis"
shall mean Isis Pharmaceuticals, Inc., a Delaware corporation, its successors and permitted assigns; 

        1.24.  "Isis
Delivery Technology" shall mean (a) Patents Controlled by Isis claiming inventions made on or before the end of the Research Term and
(b) Know-How Controlled by Isis through the end of the Research Term, that are necessary to practice within the Field; 

        1.25.  "Isis
Development Candidate Technology" shall mean Patents and/or Know-How Controlled by Isis which are necessary or useful for the
manufacture or Commercialization of the Development Product; 

        1.26.  Isis
Intellectual Property" shall mean the Isis Delivery Technology and the Isis Development Candidate Technology. For the avoidance of doubt, Isis
Intellectual Property shall exclude the Excluded Isis Technology and Orasense Collaboration Intellectual Property; 

4

 

        1.27.  "Isis
License" shall mean the Isis Drug Delivery License and the Isis Development Candidate License together. 

        1.28.  "Isis
License Agreement" shall mean this Agreement; 

        1.29.  "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; 

        1.30.  "Label",
"Labeled" or "Labeling" shall mean all labels and other written, printed or graphic matter upon (i) the Product or any container or
wrapper utilized with the Product, or (ii) any written material accompanying the Product, including, without limitation, package inserts; 

        1.31.  "Licensed
Technologies" shall mean the Elan Intellectual Property and the Isis Intellectual Property; 

        1.32.  "Licenses"
shall mean the Elan License and the Isis License; 

        1.33.  "Lien"
shall mean any and all liens, security interests, restrictions, claims, encumbrances or rights of third parties of every kind and nature; 

        1.34.  "Management
Committee" shall have the meaning given to such term in the Development Agreement; 

        1.35.  "Marketing
Authorization" shall mean any and all consents or other authorizations or approvals required from a Regulatory Authority or other governmental
authority to Commercialize a pharmaceutical product in a country in the Territory; 

        1.36.  "Net
Sales" shall mean [***] 

        1.37.  "Oligonucleotide
Drug" shall mean any single stranded, [***] at physiological pH oligonucleotide including those
[***] 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 as [***] an oligonucleotide, oligonucleotides used [***] or oligonucleotides used as [***]; 

        1.38.  "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; 

        1.39.  "Orasense"
shall mean Orasense, Ltd., a Bermuda limited company, its successors and permitted assigns; 

        1.40.  "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 2 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 2 as may be
necessary. For the avoidance of doubt, Orasense Collaboration Intellectual Property does not include any Patents and Know-How Controlled by Elan or Isis, as the case may be 

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

5

 

        1.42.  "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 Know-How Controlled by Elan or
Isis, as the case may be; 

        1.43.  "Original
Research Plan" means the Research and Development Program under that certain Subscription, Joint Development and Operating Agreement between
Elan, EIS, Isis and Orasense dated April 20, 1999; 

        1.44.  "Package",
"Packaged" and "Packaging" shall mean all primary and secondary packaging components, including, without limitation, cartons, partitions,
shippers or any other like matter used in packaging the Product; 

        1.45.  "Parties"
shall mean Elan, Isis and Orasense and "Party" shall mean Elan, Isis or Orasense; 

        1.46.  "Patents"
shall mean any and all patents and patent applications under the Control of a Party hereto. 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; 

        1.47.  "Person"
shall mean an individual, partnership, corporation, limited liability company, business trust, joint stock company, trust, unincorporated
association, joint venture, or other entity of whatever nature; 

        1.48.  "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; 

        1.49.  "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. 

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

        1.51.  "Research
Plan" shall have the meaning set forth in the Development Agreement; 

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

        1.53.  "Term"
shall have the meaning set forth in Clause 12 below; 

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

        1.55.  "United
States Dollar" and "US$" shall mean the lawful currency for the time being of the United States of America; 

        B.    Interpretation.    In this Agreement the following shall apply: 

        (1)  The
singular includes the plural and vice versa, the masculine includes the feminine and vice versa. 

        (2)  Any
reference to a Clause or Schedule shall, unless otherwise specifically provided, be to a Clause or Schedule of this Agreement. 

        (3)  The
headings of this Agreement are for ease of reference only and shall not affect its construction or interpretation. 

6

 

	2.
	GRANT OF RIGHTS.

        2.1.  Subject
to the terms and conditions contained herein and, in consideration of the payments specified under Clause 6.1, Isis hereby grants to Orasense for the
Term a non-exclusive license, including the limited right to grant sublicenses pursuant to Clause 2.5 hereof, in the Field in the Territory to the Isis Delivery Technology to
research, develop, make and have made, offer for sale, sell, import and export the Products and the Oral Platform in the Field, subject to any contractual obligations of Isis to Independent Third
Parties as of the Effective Date and, unless prohibited by the paragraph below titled Non Competition, contractual obligations to Independent Third
Parties that Isis may enter into after the Effective Date (the "Isis Drug Delivery License"); 

        2.2.  Subject
to the terms and conditions contained herein and, in consideration of the payments specified under Clause 6.1, Isis hereby grants to Orasense for the
Term an exclusive license in the Territory to the Isis Development Candidate Technology to manufacture and Commercialize the Development Product, subject to any contractual obligations of Isis to
Independent Third Parties as of the Effective Date (the "Isis Development Candidate License"). 

        2.3.  In
the event, the Isis License granted to Orasense hereunder is restricted or limited by any contractual obligations of Isis or rights of any Independent Third Parties
(a) at any time after the Effective Date or (b) as a result of a breach of the noncompetition provision under Clause 11 of the Original License Agreement, Isis shall use
reasonable commercial efforts to exclude or, where applicable, to minimize any such restriction or limitation. Except as expressly provided herein, all proprietary rights and rights of ownership with
respect to the Isis Intellectual Property shall at all times remain solely with Isis. For the avoidance of doubt, Isis shall not have any obligations to exclude or minimize any restrictions or
limitations under any agreement between an Independent Third Party and Isis entered into prior to the Effective Date, unless such restrictions or limitations arise in connection with a breach by Isis
of the noncompetition provision under Clause 11 of the Original License Agreement. 

        To
the extent royalty or other compensation obligations to Independent Third Parties that are payable with respect to Isis Intellectual Property would be triggered by the use or proposed
use of Isis Intellectual Property by Orasense, its Affiliates and/or sublicensees, Isis will inform Orasense and Elan
of such royalty or compensation obligation. If Orasense decides to utilize the Isis Intellectual Property, then Orasense will be responsible for the payment of such royalty or other compensation
obligations relating thereto. 

        2.4.  Notwithstanding
anything contained in this Agreement to the contrary, Isis shall have the right, and subject to the paragraph below titled Non-Competition,
to fully exploit and grant licenses and sublicenses with respect to the Isis Delivery Technology. Isis's rights to exploit and grant licenses referred to in the immediately preceding sentence shall
include, without limitation, the right to research, develop, license and Commercialize products. 

        2.5.  Orasense
shall not be permitted to (a) encumber any of its rights under the Licenses or the Orasense Collaboration Intellectual Property without the prior
written consent of Isis; (b) assign or sublicense any of its rights under the licenses for the Licensed Technologies and the Orasense Collaboration Intellectual Property without the prior
written consent of Isis, which consent may be withheld in Isis' sole discretion. Any agreement between Orasense and any permitted third party for the development or exploitation of the Isis
Intellectual Property shall be pursuant to a written sublicense agreement and require third party to maintain the confidentiality of all information concerning the Isis Intellectual Property (which
confidentiality obligations shall be no less onerous than the confidentiality obligations of the Parties hereunder) and shall permit an assignment of rights by Orasense to Isis in accordance with the
terms of this Agreement. Orasense shall remain responsible for all acts and omissions of any sub-licensee, as if they were acts and omissions by Orasense. Rights of permitted third party
sublicensees in and to the Isis Intellectual Property shall survive the termination 

7

 

of the license and sublicense agreements granting said intellectual property rights to Orasense; and Orasense and Isis shall in good faith agree upon the form most advantageous to Isis in which the
rights of the sublicensor under any such sublicenses are to be held (which form may include continuation of Orasense solely as the holder of such licenses or assignment of such rights to a third party
or parties, including an assignment to Isis). 

        2.6.  Orasense
and its sublicensees, if any, shall be solely responsible for ensuring that the research, development, manufacture and Commercialization of the Products within
each country of the Territory is strictly in accordance with all legal, regulatory requirements and applicable laws for each country of the Territory. 

        2.7.  When
Packaged, and to the extent permitted by law, a Label shall include an acknowledgement that the Product is made under license from Isis. Such acknowledgement shall
take into consideration all regulatory requirements and applicable laws in each country of the Territory and Orasense's reasonable commercial requirements. Orasense shall wherever possible give due
acknowledgement and recognition to Isis in all printed promotional and other material regarding the Product such as stating that the Product is under license from Isis and that the applicable Isis
Intellectual Property has been applied to the Products. Orasense shall consult with and obtain the written approval of Isis as to the format and content of any promotional and other material insofar
as it relates to a description of, or other reference to, the application of the Isis Intellectual Property, such approval not to be unreasonably withheld or delayed. The further consent of Isis shall
not be required where the format and content of
such materials is substantively similar as the materials previously furnished to and approved in writing by Isis. 

        2.8.  Isis
shall have the first option to manufacture the active ingredient of the Development Product for Orasense and meet its requirements, and Orasense shall agree to
utilize Isis as its sole supplier, subject to the customary terms and conditions contained in a supply agreement to be executed by the parties at a price equal to Isis' actual manufacturing cost plus
ten percent (10%). If, despite good faith negotiations, Isis and Orasense do not reach agreement on the terms of such manufacturing agreement within six (6) months from the Parties'
commencement of discussion of such terms, then Orasense shall be free to offer a third party terms to manufacture the active ingredient of the Development Product in the Territory, which terms when
taken as a whole, are more favorable to Orasense than the principal terms of the last written proposal offered to Orasense by Isis, or by Orasense to Isis, as the case may be. 

	3.
	INTENTIONALLY DELETED

	4.
	DEVELOPMENT OF PRODUCTS

        4.1.  Orasense
shall, or shall cause its sublicensees to, diligently pursue the research and development of the Elan Intellectual Property, Isis Intellectual Property and
Orasense Collaboration Intellectual Property and shall use its, and shall cause its sublicensees to use their, commercially reasonable efforts to Commercialize a Product. 

        4.2.  [***]. 

	5.
	REGULATORY APPROVALS

        5.1.  Orasense
shall, or shall cause its sublicensees, at its or its sublicensees' sole cost and expense, to file and shall use its reasonable best efforts to prosecute to
approval or cause its sublicensees to prosecute to approval, the Marketing Authorizations for the Products in the Territory. During any Marketing Authorization registration procedure, Orasense shall
keep Isis promptly and fully advised of Orasense's registration activities, progress and procedures with respect to the Commercialization of any Product and the Oral Platform. Orasense shall, and
shall cause its sublicensees to, inform Isis of any writings, dealings and other communications that Orasense and its sublicensees have with the FDA and any other Regulatory Authority with respect to
the safety of the Product and the Oral Platform. The Parties shall collaborate in relation to obtaining any required approvals, including Regulatory Approval of any Regulatory Authority in each
country in which Commercialization of the Product and the Oral Platform is sought for final Labeling. 

8

   
        5.2.  Subject to agreement to the contrary, any and all Marketing Authorizations filed hereunder for Products shall, to the extent owned by Orasense, remain the property of
Orasense, provided that Orasense shall allow Isis access thereto to enable Isis to research, develop and Commercialize any product outside the Field. Orasense shall maintain or cause its sublicensees
to maintain such Marketing Authorizations at its or their own cost and expense. 

        5.3.  Orasense
shall indemnify and hold harmless Isis, its agents and employees from and against all claims, damages, losses, liabilities and expenses to which Isis, its
agents, and employees may become subject related to or arising out of Orasense's bad faith, negligence or intentional misconduct in connection with the filing or maintenance of the Marketing
Authorizations. 

	6.
	FINANCIAL PROVISIONS

        6.1  In
consideration of the license to the Patents licensed to Orasense by Isis under the Isis License, Orasense shall pay to Isis, the following amounts: 

        6.1.1    Development Product Fees and Royalties.    Payments to Isis with respect to services rendered in connection
with the Development Product shall be paid as provided below and the gross profits of Orasense shall be distributed to Isis as set forth below. 

        6.1.2    Development Work  —    Research and development work performed during the Research
Term pursuant to the Research Plan contracted by Orasense to Isis shall be payable by Orasense to Isis based on fully burdened actual costs at Isis's Full Time Equivalent Rate, with annual Cost of
Living Increases. 

        6.1.3    Royalty Payments  —    After paying Elan its royalties pursuant to Section 6
of the Elan License Agreement, if any, Orasense [***] 

        6.2  Payments
pursuant to Clauses (a) and (b) above, if any, shall be made semi annually in arrears within [***] days after the expiry
of the applicable period. The method of payment shall be by wire transfer to an account specified by Isis and shall be nonrefundable to Orasense. Each payment made to Isis shall
be accompanied by a true accounting of all Products sold by Orasense, its Affiliates and its permitted sublicensees, if any, during such quarter. Such accounting shall show, on a
country-by-country and Product-by-Product basis, Net Sales, royalties received by Orasense (and the calculation thereof) and each calculation of
royalties with respect thereto, including the calculation of all adjustments and currency conversions. 

        6.3  Orasense
shall maintain and keep clear, detailed, complete, accurate and separate records for a period of [***] following the completion of such
records so: (i) as to enable any royalties which shall have accrued hereunder to be determined; and (ii) that any deductions made in arriving at the Net Sales can be determined. 

        6.4  All
payments due hereunder shall be made in United States Dollars. Payments due on Net Sales of any Product, royalties received by Orasense with respect to any Product
for each calendar quarter made in a currency other than United States Dollars shall first be calculated in the foreign currency and then converted to United States Dollars on the basis of the average
exchange rate in effect for such quarter for the purchase of United States Dollars with such foreign currency quoted in the Wall Street Journal (or comparable publication if not quoted in the Wall
Street Journal) with respect to the currency of the country of origin of such payment, determined by averaging the rates so quoted on each business day of such quarter. 

        6.5  If,
at any time, legal restrictions in the Territory prevent the prompt payment when due of royalties or any portion thereof, the Parties shall meet to discuss suitable
and reasonable alternative methods of reimbursing Isis the amount of such royalties. In the event that Orasense is prevented from making any payment under this Agreement by virtue of the statutes,
laws, codes or government regulations of the country from which the payment is to be made, then such payments may be paid by 

9

 

depositing them in the currency in which they accrue to Isis's account in a bank acceptable to Isis in the country the currency of which is involved or as otherwise agreed by the Parties. 

        6.6  Isis
and Orasense agree to co-operate in all respects necessary to take advantage of any double taxation agreements or similar agreements as may, from time
to time, be available. 

        6.7  Any
taxes payable by Isis on any payment made to Isis pursuant to this Agreement shall be for the account of Isis. If so required by applicable law, any payment made
pursuant to this Agreement shall be made by Orasense after deduction of the appropriate withholding tax, in which event the Parties shall co-operate to obtain the appropriate tax clearance
as soon as is practicable. On receipt of such clearance, Orasense shall forthwith procure that the amount so withheld is paid to Isis. 

        6.8  Orasense
shall, not more than [***] in each calendar year, permit Isis or its duly authorized representatives upon reasonable notice and at any
reasonable time during normal business hours to
have access to inspect and audit the accounts and records of Orasense and any other book, record, voucher, receipt or invoice relating to the calculation of the royalty payments on Net Sales submitted
to Isis. Any such inspection of Orasense's records shall be at the expense of Isis, except that if any such inspection reveals a deficiency in the amount of the royalty actually paid to Isis hereunder
in any calendar quarter [***] or more of the amount of any royalty actually due to Isis hereunder, then the expense of such inspection shall be borne solely by Orasense. Any
amount of deficiency shall be paid promptly to Isis by Orasense. If such inspection reveals a surplus in the amount of royalties actually paid to Isis by Orasense, Isis shall reimburse Orasense the
surplus within fifteen (15) days after determination. 

        6.9  In
the event of any unresolved dispute regarding any alleged deficiency or overpayment of royalty payments hereunder, the matter will be subject to resolution in
accordance with Clause 24.9 of the Development Agreement, which is incorporated by reference and shall for such purposes survive termination of the Development Agreement. 

	7.
	CONFIDENTIAL INFORMATION

        7.1.  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. 

        7.2.  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 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. 

        7.3.  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 

10

 

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. 

        7.4.  Any
breach of this Clause 7 by any of the Persons informed by one of the Parties is considered a breach by the Party itself. 

        7.5.  Confidential
Information shall not be deemed to include: 

        7.5.1.  information
that is generally available to the public; 

        7.5.2.  information
which is made public by the disclosing Party; 

        7.5.3.  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; 

        7.5.4.  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; 

        7.5.5.  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; 

        7.5.6.  information
which the receiving Party is required to disclose pursuant to: 

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

        7.5.6.2.  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; 

        7.5.7.  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; or 

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

        7.6.  The
provisions relating to confidentiality in this Clause 7 shall remain in effect during the term of this Agreement, and for a period of
[***] following the expiration or earlier 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. 

11

 

        7.7.  The
Parties agree that the obligations of this Clause 7 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 7, 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. 

        7.8.  Each
of the Parties shall be entitled to provide a copy of this Agreement (and any subsequent amendments hereto) and the Development Agreement 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 7. 

	8.
	WARRANTIES AND INDEMNITIES

        8.1  Isis
represents and warrants to Orasense as of the Original Effective Date that: 

        8.1.1  Isis
is a corporation duly organized 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; 

        8.1.2  Isis
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 Isis. This Agreement is the valid and binding obligation of Isis, 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; 

        8.1.3  the
execution, delivery and performance by Isis of this Agreement will not: (i) violate any provision of applicable law, statute, rule or
regulation known by and applicable to Isis or any ruling, writ, injunction, order, judgment or decree of any court, arbitrator, administrative agency or other governmental body applicable to Isis or
any of its properties or assets; or (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 Isis to which Isis is a party, except where such violation, conflict or breach
would not, individually or in the aggregate, have an adverse material effect on the business, assets, liabilities (contingent or otherwise), operations, condition (financial or otherwise), or
prospects of Isis; 

        8.1.4  to
Isis's best knowledge, except as set forth on Schedule 3 hereto, (i) Isis has the right to grant the Isis License, (ii) there are
no agreements between Isis and any third parties that conflict with the Isis License which would have a material adverse effect on the ability of Orasense to conduct its business as presently proposed
to be conducted, (iii) Isis is the owner or licensee of all rights, title and interest in the Isis Intellectual Property; and (v) [***] 

12

 

        8.2  Orasense
represents and warrants to Isis as of the Original Effective Date that: 

        8.2.1  Orasense
is duly and validly existing in good standing in the jurisdiction of its incorporation and each other jurisdiction in which the conduct of its
business requires such qualification (except where such failure to so qualify shall not have a material adverse affect on the business and assets of Orasense), and Orasense is in compliance with all
applicable laws, rules, regulations or orders relating to its business and assets; 

        8.2.2  Orasense
has full corporate authority to execute and deliver this Agreement and to consummate the transactions contemplated hereby; this Agreement has
been duly executed and delivered and constitutes the legal and valid obligations of Orasense and is enforceable against Orasense in accordance with its terms; and the execution, delivery and
performance of this Agreement and the transactions contemplated hereby will not violate or result in a default under or creation of lien or encumbrance under Orasense's certificate of incorporation,
by-laws or other organizational documents, any material agreement or instrument binding upon or affecting Orasense, or its properties or assets or any applicable laws, rules, regulations
or orders affecting Orasense or its properties or assets; 

        8.2.3  Orasense
is not in default of its charter or by-laws, any applicable laws or regulations or any material contract or agreement binding upon
or affecting it or its properties or assets and the execution, delivery and performance of this Agreement and the transactions contemplated hereby will not result in any such violation; 

        8.2.4  Orasense
represents and warrants to Elan that the execution of this Agreement by Orasense and the full performance and enjoyment of the rights of
Orasense under this Agreement will not breach the terms and conditions of any license, contract, understanding or agreement, whether express, implied, written or oral between Orasense and any third
party; 

        8.2.5  Orasense
represents and warrants to and covenants with Isis that it has the sole, exclusive and unencumbered right to grant the licenses and rights
herein granted to Isis and that it has not granted and will not grant any option, license, right or interest in or to the Isis Intellectual Property, the Orasense Collaboration Intellectual Property,
or other property to any third party which would conflict with the rights granted by this Agreement; 

        8.2.6  the
Products shall be developed, manufactured, transported, stored, handled, Packaged, marketed, promoted, distributed, offered for sale, sold and
otherwise Commercialized in accordance with all regulations and requirements of the FDA and foreign governmental authorities having jurisdiction in such country or countries in the Territory
including, without limitation, cGCP, cGLP, cGMP regulations. 

        8.2.7  the
Products shall not be adulterated or misbranded as defined by the Federal Food, Drug and Cosmetic Act (or applicable foreign law) and shall not be a
product which would violate any section of such Act if introduced in interstate commerce; 

        8.2.8  it
is fully cognizant of all applicable statutes, ordinances and regulations of the United States of America and countries in the Territory with respect
to the manufacture of the Products including, but not limited to, the U.S. Federal Food, Drug and Cosmetic Act and regulations thereunder and similar statutes in countries outside of the United
States. Orasense shall manufacture or procure the manufacture of the Products in conformity with the Marketing Authorizations and in a manner which fully complies with all United States of America and
foreign statutes, ordinances, regulations and practices. 

        8.3  In
addition to any other indemnifications provided for herein, Isis shall indemnify and hold harmless Orasense and their respective employees, agents, partners, officers
and directors from and against any claims, losses, liabilities or damages (including reasonable attorney's fees and expenses) 

13

 

incurred or sustained by Orasense arising out of or in connection with any (a) breach of any representation, covenant, warranty or obligation by Isis hereunder, or (b) any act or
omission on the part of Isis or any of its agents or employees in the performance of this Agreement. 

        8.4  In
addition to any other indemnifications provided for herein, Orasense shall indemnify and hold harmless Isis and its employees, agents, partners, officers and
directors (each an "Indemnified Party") from and against any claims, losses, liabilities or damages (including reasonable attorney's fees and expenses) incurred or sustained by an Indemnified Party
arising out of or in connection with any (a) breach of any representation, covenant, warranty or obligation by Orasense or its sublicensees hereunder, or (b) any act or omission on the
part of Orasense in connection with the research, development, manufacture and/or Commercialization of any Product hereunder, including without limitation, with respect to the conduct of any clinical
trials and death or injury to any person. 

        8.5  Orasense
shall each obtain prior to conducting any clinical trial in respect of the Product appropriate comprehensive general liability insurance and/or other insurance
coverage (the "Policies"), and shall each maintain such Policies during such clinical trials and for a period of five years thereafter. Orasense shall furnish to Isis copies of all Policies which each
holds in respect of such clinical trials. 

        8.6  Any
Party seeking an indemnity hereunder shall: 

        8.6.1  fully
and promptly notify the other Party of any claim or proceeding, or threatened claim or proceeding; 

        8.6.2  permit
the indemnifying Party to take full care and control of such claim or proceeding; 

        8.6.3  cooperate
in the investigation and defense of such claim or proceeding; 

        8.6.4  not
compromise or otherwise settle any such claim or proceeding without the prior written consent of the other Party, which consent shall not be
unreasonably withheld, conditioned or delayed; and 

        8.6.5  take
all reasonable steps to mitigate any loss or liability in respect of any such claim or proceeding. 

        8.7  NOTWITHSTANDING ANYTHING TO THE CONTRARY IN THIS AGREEMENT, ISIS, ELAN AND ORASENSE SHALL NOT BE LIABLE TO THE OTHER PARTIES, BY REASON OF ANY
REPRESENTATION OR WARRANTY, CONDITION OR OTHER TERM OR ANY DUTY OF COMMON LAW, OR UNDER THE EXPRESS TERMS OF THIS AGREEMENT, FOR ANY CONSEQUENTIAL, SPECIAL OR INCIDENTAL LOSS OR DAMAGE (WHETHER FOR
LOSS OF PROFIT OR OTHERWISE) AND WHETHER OCCASIONED BY THE APPLICABLE PARTY'S NEGLIGENCE OR OF ITS EMPLOYEES OR AGENTS OR OTHERWISE.

        8.8  EXCEPT AS SET FORTH IN THIS CLAUSE 8, ISIS IS GRANTING THE ISIS LICENSE HEREUNDER ON AN "AS IS" BASIS WITHOUT RECOURSE, REPRESENTATION OR
WARRANTY WHETHER EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR INFRINGEMENT OF THIRD PARTY RIGHTS, AND ALL SUCH WARRANTIES ARE EXPRESSLY
DISCLAIMED.

	9
	INTELLECTUAL PROPERTY OWNERSHIP RIGHTS

        9.1  Title
and all other ownership rights, including patent rights, relating to the Isis Intellectual Property shall belong to Isis. 

        9.2  Each
Party shall own the legal and equitable title to any invention invented by such Party that is not Orasense Intellectual Property. 

        9.3  Orasense
shall permanently mark or otherwise use reasonable efforts to cause any third party to permanently mark all Products and/or the Packaging therefor with such
license or patent notices to 

14

 

comply with the applicable laws of each country of sale of the Territory or otherwise to generally communicate the existence of any of Patents under the Isis Intellectual Property for the countries
of the Territory and in such manner as Isis may reasonably request in writing following receipt of written notice by Orasense of its intent to Commercialize a Product. 

        9.4  Isis,
at its expense, shall (i) secure the grant of any material patent applications in the Territory to the Isis Delivery Technology that relate to the Field and
the Isis Development Candidate Technology; (ii) defend all such applications against third party oppositions; and (iii) maintain in force any material issued letters patent within the
Isis Delivery Technology that relate to the Field and the Isis Development Candidate Patents. Isis shall have the right in its discretion to control such filing, prosecution, defense and maintenance
provided that Orasense and Elan at their request shall be provided with copies of all documents relating to such filing, prosecution, defense and maintenance in sufficient time to review such
documents and comment thereon prior to filing. 

        9.5  In
the event that Isis informs Orasense and Elan that it does not intend to file patent applications on patentable inventions and discoveries within the Isis
Intellectual Property that relate to the Field in one or more countries in the Territory or fails to file such an application within a reasonable period of time, Orasense shall have the option at its
expense to file and prosecute such patent application(s) in the joint names of Orasense and Isis. Upon written request from Orasense, Isis shall execute all documents, forms and declarations and to do
all things as shall be reasonably necessary to enable Orasense to exercise such option. 

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

        9.7  Orasense
shall have the right to prosecute at its own expense and for its own benefit any infringements of the Patents within the Isis Intellectual Property or
misappropriation of the Isis Intellectual Property, insofar as such infringements or misappropriation relate solely to the Field. In the event that Orasense takes such action, Orasense shall do so at
its own cost and expense. At Orasense's request, Isis shall cooperate with such action. Any recovery in relation to such infringement proceeding shall belong to Orasense. Should Orasense decide not to
pursue such infringers, within a reasonable period but in any event within [***] after receiving written notice of such alleged infringement or misappropriation Isis may in its
discretion initiate such proceedings in its own name, at its expense and for its own benefit, and at Isis's request, Orasense shall cooperate with such action. Alternatively, Orasense and Isis may
agree to institute such proceedings in their joint names and shall reach agreement as to the proportion in which they shall share the proceeds of any such proceedings, and the expense of any costs not
recovered, or the costs or damages payable to the third party. If the infringement of the Patents within the Isis Intellectual Property affects both the Field as well as other products being developed
or commercialized by Isis or its commercial partners outside the Field, Orasense and Isis shall endeavor to agree as to the manner in which the proceedings should be instituted and as to the
proportion in which they shall share the proceeds of any such proceedings, and the expense of any costs not recovered, or the costs or damages payable to the third party. 

	10
	RIGHTS EXPLOITATION OUTSIDE THE FIELD

        10.1    Licenses to Orasense.    Subject to the Non-Competition provisions in Clause 11 hereof,
Orasense hereby grants to Isis for the Term: 

        10.1.1  an
exclusive, royalty free and sublicensable license to practice the Orasense Collaboration Intellectual Property in the Field in the Territory; 

15

 

        10.1.2  an
exclusive, royalty free and sublicensable license to practice the Orasense Post-Collaboration Intellectual Property, and 

        10.1.3  a
[***], royalty free and sublicensable license with Elan to practice Orasense Collaboration Intellectual Property
[***] in the Territory. 

	11
	NON-COMPETITION

        During
[***], Isis shall not develop or Commercialize, or assist in the development or Commercialization of an [***], except
(a) for or on behalf of Orasense, or (b) with the prior written, unanimous consent of the Management Committee. During the Research Term and provided that Orasense is maintaining an
active program for the development and Commercialization of the Development Candidate in the Field, Isis shall not develop or Commercialize or assist in the development for Commercialization
[***] Nothing contained herein shall be construed as (i) limiting the activities of an existing third party licensee of Isis from developing Oligonucleotide Drugs
utilizing Isis Delivery Technology to the extent such rights have been previously granted by Isis, provided Isis does not provide any active support to any such activities in excess of its existing
contractual obligations or (ii) prohibiting Isis from licensing Isis Delivery Technology to an Independent Third Party or limiting the activities of any such future Independent Third Party
licensee of Isis from developing [***] utilizing Isis Delivery Technology [***]. 

	12
	TERM AND TERMINATION OF AGREEMENT

        12.1   The
term of this Agreement and the term of the Isis License granted hereunder with respect to a Product utilizing or based on the Licensed Technologies
shall commence as of the Effective Date and continue, on a Product-by-Product basis and country by country basis, for the life of the Patent rights upon which such Product is
based on or utilizes in such country (the "Term"); provided, however, that all royalty and fee obligations contained herein shall survive for the greater of (i) the Term or
(ii) [***] years from the first commercial sale of such Product. 

        12.2   Nothing
contained herein shall obligate or restrict any party from utilizing public, non-proprietary information which is not subject to the
protection of applicable patent laws. 

        12.3   If
any Party breaches any material provision of this Agreement and if such breach is (i) not capable of being cured or (ii) is capable of
being cured but is not corrected within [***] after the non-breaching Party gives written notice of the breach to the breaching Party, the non-breaching
Party may terminate this Agreement immediately by giving notice of the termination to the breaching Party, effective on the date of the notice, provided,
however, that (x) if any such curable breach is not capable of being cured within [***] period, so long as the breaching Party takes substantial
steps to cure the breach promptly after receiving notice of the breach from the non-breaching party and thereafter diligently prosecutes the cure to completion as soon as is practicable,
the non-breaching Party may not terminate this Agreement so long as the breaching party is acting in good faith to rectify such breach; provided, however, that, the completion of cure may
not, in any event, exceed, [***] months from the date of receipt of notice by the breaching Party of its breach hereunder, or (y) the default involves a good faith
dispute regarding the amount of any required payment, provided any undisputed amount is timely paid, such default shall be stayed and the remainder may be withheld for a reasonable period of time not
to [***] days during which a good faith resolution of the amount owed is being pursued. 

        12.4   In
the event that the Isis License Agreement shall be terminated, at the sole option of Elan and upon written notice to Isis and Orasense, the Elan
License shall be immediately terminated. 

        12.5   In
the event of an Failure to Fund, the Isis Development Candidate License will automatically terminate and all rights in the Isis Development Candidate
Technology will revert back to Isis. 

16

 

        12.6   Upon
the occurrence of an Event of Bankruptcy with respect to Orasense, Isis or Elan, the other Party may, upon written notice to Isis and the Party with
respect to which such Event of Bankruptcy has occurred, immediately terminate the Elan License. As used in this Clause 12.5, the term "Event of Bankruptcy" relating to either Orasense or Elan
shall mean: 

        12.6.1  the
appointment of a liquidator, receiver, administrator, examiner, trustee or similar officer of either Party of it or over all or a substantial part
of its assets under the law of any applicable jurisdiction, including without limit, Bermuda, the United States of America or Ireland; or 

        12.6.2  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 limit, Bermuda, the United States of America or Ireland
(other than as part of a bona fide restructuring or reorganization), is filed, and is not discharged within forty-five (45) days, or if either Party 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 either Party are for any
reason seized, confiscated or condemned. 

        12.7   Upon
exercise of those rights of termination as specified in Clause 12.1 to Clause 12.5 inclusive or elsewhere within this Agreement, this
Agreement shall, subject to the other provisions of this Agreement, automatically terminate forthwith and be of no further legal force or effect. 

        12.8   Upon
expiration or termination of the Agreement: 

        12.8.1  any
sums that were due from Orasense to Isis under Clause 6, including without limitation on Net Sales, in the Territory or in such particular
country or countries in the Territory (as the case may be) prior to the expiration or termination of this Agreement as set forth herein shall be paid in full within sixty (60) days after the
expiration or termination of this Agreement for the Territory or for such particular country or countries in the Territory (as the case may be); 

        12.8.2  any
provisions clearly meant to survive termination or expiration of this Agreement, including without limitation Clause 7, shall remain in full
force and effect; 

        12.8.3  all
representations, warranties and indemnities shall insofar as are appropriate remain in full force and effect; 

        12.8.4  the
rights of inspection and audit set out in Clause 12.7 shall continue in force for a period of [***]; 

        12.8.5  termination
of this Agreement for any reason shall not release any Party hereto from any liability which, at the time of such termination, has already
accrued to the other Party or which is attributable to a period prior to such termination nor preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity
with respect to any breach of this Agreement; 

        12.8.6  the
Isis Intellectual Property and all rights, licenses and sublicenses granted by Isis in and pursuant to this Agreement shall cease for the Territory
or for such particular country or countries in the Territory (as the case may be) and shall immediately revert to Isis. Following such expiration or termination, Orasense may not thereafter use in the
Territory or in such particular country or countries in the Territory (as the case may be) (a) any valid and unexpired Patents in the Isis Intellectual Property and/or (b) any Isis
Intellectual Property that remains confidential or otherwise proprietary to Isis. All rights to Orasense Intellectual Property will be transferred to and owned by Orasense. Rights of
permitted Independent Third Party sublicensees in and to the Isis Intellectual Property shall survive the termination of the license and sublicense agreements granting said intellectual property
rights to Orasense; and Orasense, Isis and Elan shall in good 

17

 

faith agree upon the form most advantageous to Elan and Isis in which the rights of the sublicensor under any such sublicenses are to be held (which form may include continuation of Orasense solely
as the holder of such licenses or assignment of such rights to a third party or parties, including an assignment to both Isis and Elan). Any sublicense agreement between Orasense and such permitted
sublicensee shall permit an assignment of rights by Orasense to Isis and shall contain additional reasonable confidentiality protections which an assignee shall reasonably require. Upon any such
assignment, Elan and Isis shall enter into good faith negotiations with respect to additional reasonable confidentiality protections which either party shall reasonably require. 

	13
	FORCE MAJEURE

        13.1   Neither
Party to this Agreement shall be liable for delay in the performance of any of its obligations hereunder if such delay results from causes beyond
its reasonable control, including, without limitation, acts of God, fires, strikes, acts of war, or intervention of a government authority, non availability of raw materials, but any such delay or
failure shall be remedied by such Party as soon as practicable; provided, however, that neither party hereunder shall be excused for delay in the performance of any of its payment obligations
hereunder. 

	14
	SETTLEMENT OF DISPUTES; GOVERNING LAW

        14.1   Any
dispute between the Parties arising out of or relating to this Agreement will be subject to resolution in accordance with Clause 24.9 of the
Development Agreement, which is incorporated by reference and shall for such purposes survive termination of the Development Agreement. 

        14.2   This
Agreement is construed under and ruled by the laws of the State of New York, without regard to the conflict of law principles. 

	15
	ASSIGNMENT

        This
Agreement may not be assigned by either Party without the prior written consent of the other, which consent shall not be unreasonably withheld, conditioned or delayed, save that
(i) either Party may assign this Agreement to its Affiliate without such consent, provided that such assignment does not have any adverse tax consequences on the other Party, and (ii) 
Isis may assign its rights and obligations hereunder in connection with a sale of its business or sale of any of the Isis Intellectual Property
licensed hereunder, whether by merger, sale of stock, sale of assets or otherwise. Isis, Elan and Orasense will discuss any assignment by either Party to an Affiliate prior to its implementation in
order to avoid or reduce any additional tax liability to the other Party resulting solely from different tax law provisions applying after such assignment to an Affiliate. For the purpose hereof, an
additional tax liability shall be deemed to have occurred if either Party would be subject to a higher net tax on payments made hereunder after taking into account any applicable tax treaty and
available tax credits than such Party was subject to before the proposed assignment. Notwithstanding any assignment hereof to an Affiliate, each Party will remain fully liable hereunder. 

18

 

	16
	NOTICES

        16.1   Any
notice to be given under this Agreement shall be sent in writing in English by registered airmail or telefaxed to the following addresses: 

	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
	

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

or
to such other address(es) and telefax numbers as may from time to time be notified by either Party to the other hereunder. 

        16.2   All
notices and other communications given to any Party hereto in accordance with the provisions of this Agreement will be deemed to have been given on
the date of receipt if delivered by hand or overnight courier service or sent by confirmed telecopy to such Party as provided in this Clause or in accordance with the latest unrevoked direction from
such Party given in accordance with this Clause 16. 

	17
	MISCELLANEOUS CLAUSES

        17.1   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 other breach or failure to perform or of any other right arising under this Agreement. 

        17.2   If
any provision in this Agreement is agreed by the Parties to be, or is deemed to be, or becomes invalid, illegal, void or unenforceable under any law
that is applicable hereto, 

19

 

        17.2.1  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 earlier date as the Parties may agree; and 

        17.2.2  the
validity, legality and enforceability of the remaining provisions of this Agreement shall not be impaired or affected in any way. 

        17.3   The
Parties shall use their respective reasonable endeavors to ensure that the Parties and any necessary third party shall execute and perform all such
further deeds, documents, assurances, acts and things as any of the Parties hereto may reasonably require by notice in writing to the other Party or such third party to carry the provisions of this
Agreement. 

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

        17.5   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 the Parties
unless specifically referred to, and solely to the extent provided, in any such other agreement. In the event of a conflict between the provisions of this Agreement and the provisions of the
Development Agreement, the terms of this Agreement shall prevail. 

        17.6   No
amendment, modification or addition hereto shall be effective or binding on either Party unless set forth in writing and executed by a duly authorized
representative of each Party. Amendments hereto shall be subject to the prior approval of Elan, which approval shall not be unreasonably withheld or delayed. 

        17.7   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. 

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

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

        17.10  Nothing
contained in this Agreement is intended or is to be construed to constitute Elan, Isis and Orasense as partners, or Isis as an employee of
Orasense and Elan, or Orasense and Elan as an employee of Isis. Neither 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 the other Party or to bind the other Party to any contract, agreement or undertaking with any third party. 

20

   
        IN WITNESS WHEREOF, the Parties hereto have executed this Agreement as of the date first set forth above. 

	 	ELAN CORPORATION, PLC	 	 	ISIS PHARMACEUTICAL, INC.
	

By:	

/s/  KEVIN INSLEY      
	
 	

By:	

/s/  B. LYNNE PARSHALL      

	

 	

Kevin Insley
 Name	
 	

 	

B. Lynne Parshall
 Name
	

 	

 Title Authorized Signatory	
 	

 	

 Title Executive VP, CFO, Director
	

 	

 Date	
 	

 	

 Date October 24, 2002
	

 	
ORASENSE, LTD.	
 	

 	

 
	

By:	

/s/  E.C. (NED) JACKSON      
	
 	

 	

 
	

 	

E.C. (Ned) Jackson
 Name	
 	

 	

 
	

 	

 Title	
 	

 	

 
	

 	

 Date	
 	

 	

 

21

   EXHIBIT A  

 Description of Development Candidate  

        [***]

22

   SCHEDULE 1A  

 Isis Intellectual Property

(Isis Development Candidate Technology)  

        [***] 

23

   SCHEDULE 2  

 ORASENSE COLLABORATION INTELLECTUAL PROPERTY  

        [***] 

24

   SCHEDULE 3  

 Isis Exceptions and Disclosures  

        [***] 

25

QuickLinks

AMENDED AND RESTATED LICENSE AGREEMENT BY AND BETWEEN ORASENSE LTD A Bermuda Limited Company ISIS PHARMACEUTICALS, INC A Delaware Corporation AND ELAN CORPORATION, PLC A Public Irish Company October 24,
2002

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