Document:

Collaboration Agreement between the Registrant & OctoPlus Technologies B.V.

 Exhibit 10.8 
 EXECUTION COPY 
 COLLABORATION AGREEMENT 
 THIS AGREEMENT, effective as of February 11, 2005 (“Effective Date”) by and between 
 BIOLEX Inc., a
company organized under the laws of the State of Delaware, U.S.A. and having a principal place of business at 158 Credle Street, Pittsboro, North Carolina 27312, U.S.A (“BIOLEX” or “Party”) 
 and 
 OCTOPLUS Technologies B.V., a company organized under the laws
of The Netherlands, having a principal place of business at Zernikedreef 12, 2333 CL Leiden, The Netherlands (“OCTOPLUS” or “Party”). 
 BACKGROUND 
 OCTOPLUS and BIOLEX have signed a Feasibility Study Agreement dated May 3, 2004 (“Feasibility
Agreement”) for a co-operative feasibility program aimed at developing a controlled release formulation based on OCTOPLUS’s proprietary release technology PolyActiveTM, containing BIOLEX’s proprietary interferon-alfa 2B active
substance produced in BIOLEX’s proprietary LEX SystemTM. 
 BIOLEX and OCTOPLUS now wish to collaborate to develop a controlled release formulation
further through a Phase II clinical trial and thereafter to commercialize a controlled release product through one or more Third Parties, and intend to do so by carrying out the Preliminary Development Program, the Primary Development Program, and
the Commercialization Program contemplated by this Agreement. 
 Certain of the OCTOPLUS Technology is licensed to OCTOPLUS by OctoPlus Sciences, B.V.
(“SCIENCES”), a subsidiary of OctoShare B.V. (“OCTOSHARE”), which in turn is the corporate parent of OCTOPLUS. As a condition to BIOLEX’s entering into this Agreement, and in its capacity as the corporate parent of OCTOPLUS,
OCTOSHARE has agreed to ensure the performance by OCTOPLUS of its obligations under the Feasibility Study Agreement and under this Agreement, and to cause SCIENCES and its other applicable Affiliates to cooperate with OCTOPLUS in fulfilling such
obligations, as set forth in a separate Collaboration Support Agreement dated February 11, 2005. 
 NOW THEREFORE, in consideration of the premises and
mutual covenants and conditions set forth herein, the Parties agree as follows: 
 1. DEFINITIONS 
  

	1.1	“Active Ingredient” means BIOLEX’s proprietary substance interferon-alfa 2B (rhIFN-A) produced in BIOLEX’s proprietary Lemna based LEX SystemTM.

  

	1.2	“Affiliate” means any entity that directly or indirectly controls, is controlled by or is under common control with a Party to this Agreement. “Control”
for the purpose of this Section 1.2 only means the ownership of more than 50% of the outstanding voting stock of a corporate entity or voting interest in a non-corporate entity. 

  

	1.3	“BIOLEX Background IP” means BIOLEX Background Know-How and BIOLEX Background Patents. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

	1.4	“BIOLEX Background Know-How” means proprietary information owned or Controlled by BIOLEX from time to time regarding the BIOLEX Technology and the general
development and manufacture of recombinant therapeutic proteins, products and related technologies. 

  

	1.5	“BIOLEX Background Patents” means any patents or patent applications owned or Controlled by BIOLEX from time to time regarding the BIOLEX Technology, its
manufacturing and use, including without limitation the patents and patent applications listed in Annex 1; any patents or patent applications based on BIOLEX Sole Inventions; and any and all patents maturing from these applications or
maturing from applications that are divisionals, continuations or continuations-in-part of these applications, foreign equivalents of the foregoing and any and all reissues or extensions of any of the foregoing. BIOLEX will report these to OCTOPLUS
in writing from time to time. 

  

	1.6	“BIOLEX Sole Inventions” has the meaning set forth in Section 7.2.3. 

  

	1.7	“BIOLEX Technology” means the Active Ingredient and BIOLEX’s proprietary Lemna based LEX SystemTM, including without limitation as claimed and described in
the BIOLEX Background Patents, as modified and improved from time to time. 

  

	1.8	“Commercialization” means developing, conducting preclinical or clinical studies or trials, seeking regulatory approvals, marketing, distributing, importing,
offering for sale or selling products. Such term also shall refer to manufacturing of the Active Ingredient or the Product if any manufacturing rights have been transferred under Sections 6.3.2 or 6.3.3, as applicable. 

  

	1.9	“Commercialization Program” has the meaning set forth in Section 6.1. 

  

	1.10	“Commercially Reasonable Efforts” means, as applied to a Party, those efforts and resources equivalent to that level of attention, care, funding and manpower that
they devote to their other businesses and products of similar commercial potential and at a similar stage in development or product life. 

  

	1.11	“Competitor” has the meaning set forth in Section 6.6. 

  

	1.12	“Controlled” means the possession of the legal right to grant a license or sublicense to a particular item, material, know-how or Intellectual Property right
without violating the terms of any agreement or other arrangement with any Third Party. 

  

	1.13	“Damages” has the meaning set forth in Section 9.4. 

  

	1.14	“Developed” has the meaning set forth in Section 7.2. 

  

	1.15	“Feasibility Agreement” has the meaning set forth in the Background Section above. 

  

	1.16	“IND” means a Notice of Claimed Investigational Exemption for a New Drug, as such term is used under the United States Federal Food, Drug and Cosmetic Act, as
amended from time to time, including all regulations promulgated thereunder. 

  

	1.17	“Intellectual Property” means any patent, know-how, trade secret or other intellectual property of a Party. 

  

	1.18	“Joint Invention” has the meaning set forth in Section 7.2.4. 

  

	1.19	“Joint Invention Patent” has the meaning set forth in Section 7.8. 

  

	1.20	“Manufacturing Costs” has the meaning set forth in Annex 3. 

  

	1.21	“Manufacturing Profits” has the meaning set forth in Annex 3. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 2 

	1.22	“OCTOPLUS Background IP” means OCTOPLUS Background Know-How and OCTOPLUS Background Patents. 

  

	1.23	“OCTOPLUS Background Know-How” means proprietary information owned or Controlled by OCTOPLUS from time to time regarding the general development and manufacture of
biodegradable microsphere-based formulations for controlled parenteral release of biopharmaceutical products and related technologies. 

  

	1.24	“OCTOPLUS Background Patents” means any patents or patent applications owned or Controlled by OCTOPLUS from time to time regarding OCTOPLUS Technology, its
manufacturing and use, including without limitation the patents and patent applications listed in Annex 1; any patents or patent applications based on OCTOPLUS Sole Inventions; and any and all patents maturing from these applications or
maturing from applications that are divisionals, continuations or continuations-in-part of these applications, foreign equivalents of the foregoing and any and all reissues or extensions of any of the foregoing. OCTOPLUS will report these to BIOLEX
in writing from time to time. 

  

	1.25	“OCTOPLUS Sole Inventions” has the meaning set forth in Section 7.2.3. 

  

	 1.26
	 “OCTOPLUS Technology” means OCTOPLUS’s proprietary PolyActiveTM technology, including without limitation as claimed and described in the OCTOPLUS Background Patents, as modified and improved from time to time. 

  

	1.27	“Phase I Clinical Trials” has the meaning set forth in Section 2.1. 

  

	1.28	“Preliminary Development Program” has the meaning set forth in Section 2.1. 

  

	1.29	“Primary Development Program” has the meaning set forth in Section 5.1.1. 

  

	1.30	“Product” means any controlled release formulation developed under the Feasibility Agreement or this Agreement based on the Active Ingredient and the OCTOPLUS
Technology. 

  

	1.31	“Specifications” means the written specifications developed by the Steering Committee from time to time for Active Ingredient, Products or components of Products
and for the manufacturing and quality control of Active Ingredient or Products for preclinical or clinical use. 

  

	1.32	“Steering Committee” has the meaning set forth in Section 3.1. 

  

	1.33	“Step Out Deadline” has the meaning set forth in Section 4.3. 

  

	1.34	“Term” has the meaning set forth in Section 10.1. 

  

	1.35	“Third Party” means any person that is not a Party or an Affiliate of a Party hereto. 

  

	1.36	“Unmodified Alfa-Interferon” means any protein comprising an alfa interferon protein sequence that is naturally occurring in humans or approved for human use as of
the Effective Date anywhere in the world (including without limitation Intron-A, Peg-Intron, Roferon, Pegasys, and Infergen), plus or minus up to ten (10) amino acids from the C-terminus and whether including or lacking an N-terminal
methionine. 

 2. OVERVIEW OF COLLABORATION 
  

	2.1	 Collaboration Objectives and Overview. Pursuant to the Feasibility Agreement, the Parties have undertaken preliminary research and development activities
related to the commercial and technical feasibility of the Product. OCTOPLUS is 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
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responsible under the Feasibility Agreement for completing a Phase I clinical trial with respect to the Product at its sole expense. Independent of the
Feasibility Agreement, BIOLEX is conducting a Phase I clinical trial with respect to the Active Ingredient at its sole expense (collectively with the OCTOPLUS Phase I clinical trial, the “Phase I Clinical Trials”). Each of the
Parties will use Commercially Reasonable Efforts to complete its Phase I Clinical Trials according to its schedule in effect as of the Effective Date, then promptly share with the other Party all data, documentation and results related to such Phase
I Clinical Trial (the “Preliminary Development Program”). Thereafter each of the Parties will decide whether to proceed with further development of the Product, including a Phase II clinical trial under an IND. If both Parties
choose to proceed with further development, the Parties will do so jointly through a Primary Development Program (as described more fully in Article 5). If either Party elects instead to step out of further development, the other Party may proceed
with the Primary Development Program alone. Following successful completion of the Primary Development Program, the Party or Parties that conducted the Primary Development Program will seek to identify and enter into collaborative arrangements with
one or more Third Parties for further development of Product(s) and the worldwide Commercialization of Product(s) under a Commercialization Program. The Parties will share equally in all profits in connection with the Commercialization Program as
specified herein unless one of the Parties steps out of participating in the Primary Development Program, in which case the profit sharing allocation will be subject to adjustment as specified elsewhere herein. 

  

	1.0	Exclusive Projects. 

  

	 	1.0.0	Except as contemplated herein, during the Term, each Party shall not directly or indirectly engage, either individually or jointly with a Third Party or Third Parties, and shall
cause its Affiliates, and its and their officers, directors, employees, agents and other representatives, not to engage, in any activities, including but not limited to research, testing, analyses, and the like, and shall not negotiate or execute
any agreement or understanding, whether oral or written, in connection with the Commercialization or manufacture of Unmodified Alfa-Interferon (i) using or otherwise involving the OCTOPLUS Technology in any way; or (ii) that is to
be administered to humans less frequently than once every six (6) days, regardless of the underlying technology. 

  

	 	2.0.0	Notwithstanding the foregoing, OctoPlus Development B.V., an Affiliate of OCTOPLUS, may provide services to Third Parties on any Unmodified Alfa-Interferon to be administered less
frequently than once every six (6) days or for which the administration frequency is not known prior to providing such services to such Third Party, solely on a bona fide fee-for-services basis as part of OctoPlus Development B.V.’s normal
fee-for-service business activities at its general commercial rates and conditions, provided: (i) such services do not involve application of or access to any proprietary OCTOPLUS technology, including without limitation the OCTOPLUS
PolyActiveTM or OctoDexTM technology, as constituted from time to time; (ii) OCTOPLUS notifies BIOLEX of the proposed services in writing in advance, including a summary (not inconsistent with OCTOPLUS’s confidentiality obligations
to such Third Parties) of the services proposed to be rendered; and (iii) BIOLEX does not object within five (5) business days after receipt of such notice to the rendering of such services. BIOLEX agrees to consider each such proposal in
good faith, and OCTOPLUS acknowledges that limitations on OCTOPLUS’s authority to provide information about the nature of such services may cause BIOLEX to object based on the resulting uncertainty about the possible impact rendering the
services could have on the collaboration contemplated by this Agreement. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 4 

 3. STEERING COMMITTEE 
  

	3.1	Steering Committee. The Parties shall establish a group (the “Steering Committee”) for the primary control over the direction and the course of the
activities under this Agreement, including business development with regard to Third Parties. 

  

	3.2	Responsibility. The Steering Committee shall be responsible for planning and monitoring the activities hereunder and may modify tasks, responsibilities and budgets set forth
in Annex 2, and/or the corresponding Specifications, as appropriate. In addition, the Steering Committee may modify the definitions of BIOLEX Manufacturing Costs and OCTOPLUS Manufacturing Costs set forth in Annex 3, or the application
of these terms hereunder, as appropriate. It is also the responsibility of the Steering Committee to facilitate communications between the Parties. The Steering Committee shall have no authority to amend or waive compliance with the terms and
conditions of this Agreement, or to approve actions of the Parties which are inconsistent with this Agreement. Any such waivers or amendments shall be implemented only as described in Sections 11.14 or 11.15, as applicable, except that the Steering
Committee may amend Annex 2 or Annex 3 or waive compliance with any part of Annex 2 in a manner that is consistent with this Agreement without complying with Sections 11.14 or 11.15. 

  

	3.3	Representation. The Steering Committee shall be composed of an equal number of representatives from both Parties. The chairperson of the Steering Committee shall be
designated semi-annually on an alternating basis between the Parties. The initial chairperson will be designated by OCTOPLUS through the end of June 2005. 

  

	3.4	Meetings. The Steering Committee shall meet at least once (1) monthly and otherwise as appropriate, by teleconference or videoconference or in person, to review the
progress of the activities hereunder, to establish that the tasks and responsibilities and time schedule set forth in Annex 2 are correct and, if not, determine what modifications to same are required, and to take such other action as the
Steering Committee considers appropriate. The Steering Committee shall meet at least once (1) every six (6) months in person, with the location of such meetings to alternate between the respective sites of the Parties and the first meeting
to take place at BIOLEX’s site. Each Party shall be responsible for any and all travel and related expenses incurred by its representatives in connection with such meetings. Minutes shall be maintained by the Steering Committee for its
meetings. The chairperson will be responsible for preparing and circulating draft minutes for approval by the Steering Committee. 

  

	3.5	Decisions. All decisions, including consents, approvals, authorizations, directions or recommendations of the Steering Committee shall be made during meetings or by unanimous
written consent. Decisions made during any meeting, including those held by teleconference or videoconference method, shall require that both Parties be represented at such meeting and the decision be approved unanimously by the members of the
Steering Committee in attendance, provided, however, that if one Party has stepped out as described in Section 5.3, all such decisions thereafter shall be made only by the unanimous consent of the representatives of the Party that has not
stepped out. The Parties shall both use Commercially Reasonable Efforts and shall work in good faith and fair dealings to reach agreement within the Steering Committee. The Steering Committee also may act without a meeting provided that the decision
is evidenced by unanimous written consent of all Steering Committee members. 

  

	3.6	Deadlocks. 

  

	 	3.6.1	 In the event of a deadlock regarding a proposed decision of the Steering Committee, the Parties’ respective Steering Committee representatives shall meet,
either in person or telephonically, to negotiate in good faith a mutually acceptable resolution to the deadlock. If the deadlock still cannot be resolved, either Party’s representatives may refer 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 5 

	 	 
the matter to the President of OCTOPLUS and the President of BIOLEX for resolution by delivering a written notice to that effect to the other Party.
Thereafter, the Presidents shall meet, either in person or telephonically, to negotiate in good faith a mutually acceptable resolution to the deadlock. If the Parties’ respective Presidents cannot reach agreement within two (2) weeks
following the date of written notice, then either Party may initiate non-binding mediation pursuant to Section 3.6.2 as a further method to attempt to resolve the deadlock. For the avoidance of doubt: (a) a dispute regarding the rights or
obligations of either Party under this Agreement is not a deadlock subject to resolution under this Section (but would be subject to resolution under Section 11.7); and (b) a Party’s decision not to consent to an action over which
this Agreement specifically requires the Party’s consent, or not to engage in conduct requested by the other Party that is outside the scope of this Agreement, is not a deadlock subject to resolution under this Section.

  

	 	3.6.2	In the event of a deadlock that cannot be resolved by the Parties’ respective Presidents, either Party may initiate non-binding mediation by providing written notice to the
other Party (a “Mediation Notice”), which shall contain a list of five (5) recommended individuals to serve as the mediator. Within five (5) days thereafter, the other Party shall respond by written notice to the Party
initiating mediation, providing a list of five (5) recommended individuals to serve as the mediator. The recommended mediators shall be individuals with experience in the pharmaceutical or biotechnology industries. If, within ten (10) days
after receipt of the Mediation Notice, the Parties shall have agreed upon an individual to serve as mediator, the mediator shall conduct a mediation in an effort to resolve the dispute, employing commercially reasonable procedures selected by the
mediator in consultation with the Parties, completing such mediation no later than ten (10) days after engagement. If the Parties have not agreed on a mediator within ten (10) days, each Party involved shall name one mediator and the two
mediators thus named shall select a third mediator to conduct the mediation in accordance with the preceding sentence. Except as otherwise agreed by the Parties, the mediation shall be conducted in London, England in the English language. If the
Parties resolve their deadlock through mediation, the mediator and the Parties jointly shall prepare a writing setting forth the terms and conditions of the resolution. The Parties shall bear their own costs in preparing for and participating in the
resolution of any deadlock under this Section 3.6.2, and the costs of mediator(s) shall be equally divided among the Parties. 

  

	 	3.6.3	Notwithstanding the procedures set forth above in this Section 3.6, in connection with the Parties’ mutual efforts to resolve any deadlock, and failing resolution in the
manner set forth above, OCTOPLUS will determine the final resolution of any deadlock concerning the execution of the Primary Development Program and the Commercialization Program as they relate solely to Europe, and BIOLEX will determine the final
resolution of any deadlock concerning the execution of the Primary Development Program and the Commercialization Program as they relate solely to North America. 

  

	3.7	Expenses. The Parties shall be responsible for expenses of their respective Steering Committee representatives related to their participation on the Steering Committee and
attendance at Steering Committee meetings. 

 4. PRELIMINARY DEVELOPMENT PROGRAM 
  

	4.1	 BIOLEX Contribution. BIOLEX will provide for use by OCTOPLUS solely in connection with the Preliminary Development Program, the Primary Development Program
and the Commercialization Program all data, results, and documentation 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 6 

	 	 
reasonably required with respect to BIOLEX Technology, including the results from its Phase I Clinical Trial. For the avoidance of doubt, BIOLEX will retain
all right, title and interest to all such materials, the BIOLEX Technology, and all corresponding Intellectual Property rights, subject only to the limited authority granted to OCTOPLUS hereunder. 

  

	4.2	OCTOPLUS Contribution. OCTOPLUS will provide for use by BIOLEX solely in connection with the Preliminary Development Program, the Primary Development Program and the
Commercialization Program all data, results, documentation reasonably required with respect to OCTOPLUS Technology, including the results from its Phase I Clinical Trial. For the avoidance of doubt, OCTOPLUS will retain all right, title and interest
to all such materials, the OCTOPLUS Technology, and all corresponding Intellectual Property rights, subject only to the limited authority granted to BIOLEX hereunder. 

  

	4.3	Completion of Phase I Clinical Trials. The Parties will use Commercially Reasonable Efforts to complete their respective Phase I Clinical Trials, and promptly will compile
all data, results, and documentation and report the results of their respective Phase I Clinical Trials to the Steering Committee. The Steering Committee thereafter will specify a deadline (which in any case shall be not later than sixty
(60) days following the completion of the Phase I Clinical Trials) (the “Step-Out Deadline”) by which each Party must provide written notice to the other of its decision to step out of further development as described in
Section 5.3. Subject to Section 5.3.2, each Party that does not provide such written notice to the other Party by the Step-Out Deadline shall be committed to participate in the Primary Development Program as described in Article 5 and
Annex 2. Notwithstanding this Section 4.3, either Party may suspend or discontinue its Phase I Clinical Trials after consultation with the other Party if (i) the Steering Committee approves such suspension or termination or
(ii) the Party believes in good faith based upon advice of legal counsel that continuing its Phase I Clinical Trial would constitute a violation of applicable law. 

 5. PRIMARY DEVELOPMENT PROGRAM 
  

	5.1	Primary Development Program. 

  

	 	5.1.1	Prior to starting a Commercialization Program with respect to any Product, the Parties/Party that have/has not stepped out as described in Section 5.3 will establish and
perform a development program for a Phase II clinical trial under an IND for Product for the indication of Hepatitis C, including corresponding pre-clinical tests and pharmaceutical development activities necessary to carry out such clinical
program, together with any and all other activities the Steering Committee determines to conduct in support of or preparation for the Commercialization Program, including but not limited to obtaining patent opinions and market research for the
Product and undertaking Product branding activities (all of the foregoing, collectively, the “Primary Development Program”). Initial tasks and responsibilities of BIOLEX and OCTOPLUS, as well as the anticipated budget, for the
Primary Development Program are specified in Annex 2. Subject to stepping out according to Section 5.3, each Party will conduct its Primary Development Program activities as specified in Annex 2 and as otherwise established by the
Steering Committee from time to time. Each Party will use Commercially Reasonable Efforts to conduct its assigned tasks and responsibilities within the budget limits specified in Annex 2 or otherwise approved by the Steering Committee, and
neither will be obligated to conduct such activities to the extent doing so would require incurring expenses beyond ten percent (10%) of the budgeted amount, thus amounting in total to 110% (one hundred and ten percent) of those amounts.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 7 

	 	5.1.2	In connection with the Primary Development Program, BIOLEX shall manufacture and supply the Active Ingredient to OCTOPLUS at BIOLEX’s sole cost and expense, and OCTOPLUS shall
manufacture and supply the Product at OCTOPLUS’s sole cost and expense (using Active Ingredient provided by BIOLEX), all as required for the completion of the Primary Development Program. 

  

	5.2	Funding of Primary Development Program. Except as otherwise provided in this Article 5 with respect to a Party that has stepped out, the following shall apply with respect to
the Primary Development Program: 

  

	 	5.2.1	All direct Third Party costs specified in Annex 2 or otherwise approved by the Steering Committee in the Primary Development Program will be shared equally between the
Parties or as otherwise set forth in Annex 2, unless agreed to otherwise in writing. The Parties will cooperate to pay any such costs to the applicable Third Party and to make adjusting payments between the Parties as needed, in coordination
through the Steering Committee. For the avoidance of doubt, none of the Parties’ respective Third Party costs incurred in connection with the Preliminary Development Program or with the manufacture and supply of Active Ingredient or Product
under Section 5.1 shall be subject to credit, sharing, reimbursement, or otherwise taken into account under the Primary Development Program or the Commercialization Program. 

  

	 	5.2.2	With respect to internal costs of the Parties incurred in connection with the Primary Development Program (including the Parties’ respective costs and expenses incurred in
connection with business development activities described in Section 5.7) that are not related to the Parties’ supply of Active Ingredient or Product, as the case may be, pursuant to Section 5.1, the Steering Committee shall monitor
the Parties’ activities and shall allocate tasks and responsibilities from time to time with the goal of avoiding unnecessary duplication by the Parties, maximizing utilization of the resources of the Parties, making the most effective use of
the Parties’ respective strengths and competencies, and ensuring to the extent practicable that the respective contributions of the Parties during the course of the Primary Development Program are approximately equal. If, at any time during the
Primary Development Program, in applying the foregoing principles for allocating tasks and responsibilities, the Steering Committee determines that it will be unable to maintain substantially equal contributions of the Parties over the entire course
of the Primary Development Program, the Steering Committee may develop and propose a plan to restore substantial equality of contributions (potentially including having one Party make adjusting payments to the other), which shall be implemented if
mutually acceptable to the Parties. For the avoidance of doubt, subject to the foregoing, none of the Parties’ respective internal costs incurred in connection with the Preliminary Development Program shall be subject to credit, sharing,
reimbursement, or otherwise taken into account under the Primary Development Program or the Commercialization Program. 

  

	5.3	Step Out/In Consequences. 

  

	 	5.3.1	Except as set forth in Section 5.3.2 or Article 10, a Party’s failure to step out by the Step-Out Deadline shall constitute that Party’s commitment to participate in
the Primary Development Program as described in this Article 5 and Annex 2 until the earlier of (i) the date that the Steering Committee determines that the Primary Development Program has been completed, or (ii) such time as the
Parties shall agree to terminate the Primary Development Program. 

  

	 	5.3.2	 If a Party elects to step out, the other Party will have the option at its own cost and expense (subject to the recovery of certain Third Party costs as described
in Section 5.4.5 or Section 5.5.5, as applicable) to take full responsibility for 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 8 

	 	 
conducting the Primary Development Program and the Commercialization Program, including entering into sub-licensing arrangements for the Product with Third
Parties, and shall provide written notice to the other Party of its decision by the later of (i) the Step-Out Deadline or (ii) thirty (30) days after it receives written notice that the other Party has stepped out (the
“Step-In Deadline”). If the Party that has not stepped out fails to provide such written notice by the Step-In Deadline, then such Party also shall be deemed to have stepped out. 

  

	 	5.3.3	If both parties step out, then either Party may terminate this Agreement as described in Section 10.3. 

  

	5.4	OCTOPLUS Steps Out. In the event OCTOPLUS steps out and BIOLEX steps in under Section 5.3, the following shall apply: 

  

	 	5.4.1	OCTOPLUS shall be responsible for one-half (1/2), or its share as otherwise set forth in Annex 2, of all Third Party costs incurred or committed as part of the Primary
Development Plan prior to stepping out. OCTOPLUS shall manufacture and supply the Product to BIOLEX at OCTOPLUS’s sole cost and expense (based on Active Ingredient provided by BIOLEX), as reasonably necessary under the Primary Development
Program, and shall remain obligated with respect to manufacture of the Product in connection with the Commercialization Program as described in Section 6.3. 

  

	 	5.4.2	Any licenses granted by BIOLEX to OCTOPLUS with respect to BIOLEX Background IP with respect to the Product shall terminate effective upon stepping out, except that in the event of
supply by OCTOPLUS of Product to Third Parties or BIOLEX in accordance with this Agreement, BIOLEX will be deemed to have granted OCTOPLUS a worldwide, non-exclusive, irrevocable license to BIOLEX Background IP solely to the extent necessary to
carry out those obligations. 

  

	 	5.4.3	Subject to Section 6.3, the Parties shall work together to ensure a smooth and orderly transition of the Product to BIOLEX, including the assignment of any contracts related to
the Product and the assumption by BIOLEX of any obligations thereunder and transfer to BIOLEX of ownership of regulatory documentation related to the Product to the extent reasonably necessary for the Commercialization of Product.

  

	 	5.4.4	Upon reasonable request, OCTOPLUS shall (i) provide BIOLEX and its licensees full access to all available data required for regulatory filings with respect to the Product at no
cost to BIOLEX, and (ii) provide BIOLEX with continued technical support and information regarding the application of OCTOPLUS Background IP to the Product to the extent reasonably necessary for the Commercialization of the Product.

  

	 	5.4.5	Notwithstanding anything to the contrary herein including in Annex 2 or Annex 3, (i) BIOLEX shall be entitled to recover all Third Party costs paid by BIOLEX that
were not shared equally or as set forth in Annex 2 by the Parties prior to any allocation of Third Party proceeds between OCTOPLUS and BIOLEX pursuant to Section 6.5; and (ii) OCTOPLUS’s share of any profits related to the
Product for purposes of any such allocation shall be reduced to twenty-five percent (25%) of such profits and BIOLEX’s share of profits shall be increased to seventy-five percent (75%) of such profits. 

  

	5.5	BIOLEX Steps Out. In the event BIOLEX steps out and OCTOPLUS steps in under Section 5.3, the following shall apply: 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 9 

	 	5.5.1	BIOLEX shall be responsible for one-half (1/2), or its share as otherwise set forth in Annex 2, of all Third Party costs incurred or committed as part of the Primary
Development Plan prior to stepping out. BIOLEX shall manufacture and supply the Active Ingredient to OCTOPLUS at BIOLEX’s sole cost and expense, as reasonably necessary under the Primary Development Plan, and shall remain obligated with respect
to manufacture of the Active Ingredient in connection with the Commercialization Program as described in Section 6.3. 

  

	 	5.5.2	Any licenses granted by OCTOPLUS to BIOLEX with respect to OCTOPLUS Background IP with respect to such Product shall terminate effective upon stepping out, subject to
Section 6.3. 

  

	 	5.5.3	Subject to Section 6.3, the Parties shall work together to ensure a smooth and orderly transition of the Product to OCTOPLUS, including the assignment of any contracts related
to the Product and the assumption by OCTOPLUS of any obligations thereunder and transfer to OCTOPLUS of ownership of regulatory documentation related to the Active Ingredient to the extent reasonably necessary for the Commercialization of Product.

  

	 	5.5.4	Upon reasonable request, BIOLEX shall (i) provide OCTOPLUS and its licensees full access to all available data required for regulatory filings with respect to the Product at no
cost to OCTOPLUS, and (ii) provide OCTOPLUS with continued technical support and information regarding the application of BIOLEX Background IP to the Product to the extent reasonably necessary for the Commercialization of the Product.

  

	 	5.5.5	Notwithstanding anything to the contrary herein including in Annex 2 or Annex 3, (i) OCTOPLUS shall be entitled to recover any direct Third Party costs paid by
OCTOPLUS that were not shared equally or as set forth in Annex 2 by the Parties prior to any allocation of Third Party proceeds between OCTOPLUS and BIOLEX pursuant to Section 6.5; and (ii) Biolex’s share of any profits related
to the Product for purposes of any such allocation shall be reduced to twenty-five percent (25%) of such profits and OCTOPLUS’s share of profits shall be increased to 75% of such profits. 

  

	5.6	Step-Out Following Commitment to Participate in Primary Development Program. 

  

	 	5.6.1	If both Parties have committed to participate in the Primary Development Program as described in Section 5.3.1, a Party may nevertheless step out at any time thereafter by
providing sixty (60) days written notice to the other Party. Stepping out on this basis will be treated for all purposes as if such Party had stepped out as described in Section 5.3, except that (i) such Party shall use Commercially
Reasonable Efforts to complete all internal work related to the Primary Development Program that is active and on-going at the time that the Party provides notice that it is stepping out, and (ii) such Party shall remain obligated under
Section 5.2.1 for fifty percent (50%), or such other share as set forth in Annex 2, of all Third Party costs incurred through the completion of the Primary Development Program that are reflected in Annex 2 as in effect on the date
such Party provided the written notice described above or that otherwise had been approved by the Steering Committee prior to such date. 

  

	 	5.6.2	If one Party has stepped out as described in Section 5.3 or in this Section 5.6 and the other Party has not theretofore stepped out, then the Party that has not stepped
out may elect to step out at any time prior to completion of the Primary Development Program by delivering notice to the other Party and immediately ceasing all Primary Development Program work, which thereafter shall be treated as if both Parties
had stepped out as described in Section 5.3.3. In such case, the financial responsibility of the first Party to have stepped out will be as specified in Section 5.4.1, 5.5.1 or 5.6.1, as applicable. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 10 

	5.7	Coordination of Business Development Efforts. 

  

	 	5.7.1	The Steering Committee shall be responsible for developing and implementing a strategy for identifying and evaluating appropriate Third Party Commercialization partners to share in
the financial risk and reward related to development and Commercialization of the Product and for coordinating the Parties’ respective efforts with respect to business development. In this regard, the Steering Committee shall propose
appropriate financial models for risk sharing with Third Party Commercialization partners and establish a prioritized listing of such prospective partners. The Steering Committee shall approve the timing and method for initial contact with such
Third Parties to solicit indications of interest with respect to the Product. The Parties may independently contact Third Parties that have been approved for contact by the Steering Committee, consistent with the priorities, timing and method
established by the Steering Committee, and each party shall keep the Steering Committee fully and timely informed concerning its business development activities. Nothing in this Section 5.7.1 shall be deemed to prevent a Party from entering
into preliminary discussions with a Third Party that has taken the initiative to contact such Party regarding a proposed partnering relationship with respect to the Product, but such Party shall provide the Steering Committee with an update
regarding the Third Party’s interest as soon as practicable thereafter and transfer responsibility for the contact to the Steering Committee regarding further communications. 

  

	 	5.7.2	Subject to Section 5.7.1 BIOLEX shall take the lead with respect to contacting prospective partners for Commercialization of Product within North America, and OCTOPLUS shall
take the lead with respect to contacting prospective partners for Commercialization of Product within Europe. BIOLEX and OCTOPLUS may each contact prospective partners for Commercialization of Product in all other territories, including Japan.

  

	5.8	Additional Development Work. Following completion of the Primary Development Program, neither Party shall, nor be obligated to, engage in further research or development
activities for the Product without the consent of the other Party. 

  

	5.9	Records. During the Term and for a period of five (5) years thereafter or such longer time required by law, BIOLEX and OCTOPLUS shall maintain records of the Preliminary
Development Program, the Primary Development Program, and the Commercialization Program (or cause such records to be maintained) in sufficient detail and good scientific manner as will properly reflect all development work done and results achieved
in such programs. Each Party shall allow the other Party to have reasonable access to all pertinent records generated by or on behalf of such Party with respect to the activities hereunder, subject to any confidentiality obligations to each other,
Third Parties, attorney-client privilege or legal restrictions. This retention of records may be extended if there is a legal proceeding pending (i.e., court action, or U.S. interference or opposition involving patent rights arising hereunder) where
those records are reasonably required and a written request with the reason is provided to the Party holding such records. In the event a Party wishes to destroy such records after the time specified above, it shall first give sixty
(60) days’ prior written notice to the other Party, and the other Party shall have the right, at its option and expense, and upon prior written notice given within such sixty (60) day period to the Party wishing to destroy such
records, to take possession of all or any portion of such records. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 11 

	5.10	Applicable Laws. Each Party shall conduct its activities under this Agreement, including without limitation with respect to the Primary Development Program, in accordance
with all applicable laws and regulations. In addition, OCTOPLUS and BIOLEX agree that all clinical research and development hereunder shall be conducted in accordance with ICH guidelines and good clinical practices. Animal care and use for any
research undertaken pursuant to this Agreement will be carried out in accordance with all applicable national or international legal guidelines for animal care and use. The Parties acknowledge as of the Effective Date that regulatory approvals
necessary for manufacturing or Commercialization of the Active Ingredient or the Product have not yet been obtained. Each Party will use Commercially Reasonable Efforts to procure any approvals required by law to conduct its respective obligations
under this Agreement, and neither will be obligated to conduct any such activity in the absence of any such corresponding required approval. 

  

	5.11	Subcontractors. Each Party shall have the right, subject to the prior written consent of the other Party, such consent not to be unreasonably withheld or delayed, to
subcontract any of its activities under the Primary Development Program to an Affiliate or Third Party, provided that it furnishes the other Party with advanced written notice thereof, which notice shall specify the work to be subcontracted, and
obtains a written undertaking from the subcontractor that it shall be subject to the applicable terms and conditions of this Agreement. All costs of subcontracting any activities to a Third Party as described in this Section 5.11 shall be the
sole obligation of the Party that engaged such Third Party, except to the extent approved as shared Third Party costs by the Steering Committee pursuant to Section 5.2. 

 6. COMMERCIALIZATION PROGRAM 
  

	6.1	Third Party Commercialization Partners. The Parties intend to identify and enter into collaborative arrangements with one or more Third Parties for further development of
Products and the worldwide Commercialization of Products following completion of the Primary Development Program (the “Commercialization Program”). It is the understanding of both Parties that the primary markets for Products are
Europe, Japan and North America and in that sense the Parties initially will focus primarily on Third Parties for Commercialization of Products in those regions in coordination through the Steering Committee. 

  

	6.2	Duty of Third Party. It is envisaged that any Third Party will fund Commercialization of Products and may provide the Parties with financial support for launch facilities or
other services. Operational funding, upfront payments, license fees, milestones, royalties or similar payments received from a Third Party will be subject to the commercial arrangements with such Third Party. 

  

	6.3	Supply of Active Ingredient and Product. 

  

	 	6.3.1	 In any arrangement with a Third Party, BIOLEX shall retain the exclusive manufacturing rights for the commercial Active Ingredient bulk product and shall use
Commercially Reasonable Efforts to enter into a commercial supply agreement with OCTOPLUS for the delivery of Active Ingredient to OCTOPLUS. In any arrangement with a Third Party, OCTOPLUS shall retain the exclusive manufacturing rights for the
commercial finished Product (based on Active Ingredient provided by BIOLEX) and shall use Commercially Reasonable Efforts to enter into a commercial supply agreement with the Third Party for the delivery of Product for the applicable market;
provided, however, that if BIOLEX has stepped in and OCTOPLUS has stepped out as described in Section 5.3, OCTOPLUS shall instead enter into such supply agreement with BIOLEX. The terms of any such supply agreements contemplated by this
Section 6.3.1 will be normal and customary and consistent with prevailing rates, terms, and conditions for comparable 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 12 

	 	 
products in the worldwide pharmaceutical industry. If BIOLEX or OCTOPLUS is unable to finalize and execute a commercial supply agreement as described above
for the Active Ingredient or the Product, as the case may be, within sixty (60) days after commencement of negotiations, either Party may invoke arbitration pursuant to Section 11.8 to determine whether the material terms of the commercial
supply agreement proposed by the Party or Third Party to be supplied thereunder are commercially reasonable and substantially consistent with current industry norms for commercial supply agreements of this nature. If the arbitrator determines that
the material terms of the proposed commercial supply agreement are commercially reasonable and substantially consistent with current industry norms for commercial supply agreements of this nature, then the intended manufacturer shall have the option
of either (i) entering into the proposed commercial supply agreement within fifteen (15) days after the arbitrator renders a decision and fulfilling its obligations thereunder or (ii) not entering into the proposed commercial supply
agreement, in which case the other Party may treat such failure as an inability or unwillingness to supply the other Party’s requirements that has not been cured within ninety (90) days of notice as described in Section 6.3.2.

  

	 	6.3.2	Notwithstanding Section 6.3.1, if BIOLEX is unable or unwilling for any reason to supply OCTOPLUS’s requirements for the Active Ingredient or OCTOPLUS is unable or
unwilling for any reason to supply BIOLEX’s requirements for the Product as contemplated by this Agreement and such inability or unwillingness results in, or is reasonably likely to have, an adverse material impact on ability of the Party to be
supplied to fulfill its responsibilities under the Preliminary Development Program, the Primary Development Program, or the Commercialization Program, then the Party to be supplied shall provide notice of such adverse material impact or the
likelihood of such adverse material impact to the intended manufacturer. If OCTOPLUS is unable or unwilling for any reason to supply the Third Party’s requirements for the Product as required by any commercial supply agreement with such Third
Party described in Section 6.3.1, then BIOLEX shall provide notice of such failure of Third Party Supply to OCTOPLUS. If uncured by the intended manufacturer within forty-five (45) days of any notice described in the first two sentences of
this Section 6.3.2, then the Party providing such notice, without prejudice to any other remedies such Party may have under this Agreement or otherwise, shall have the right to manufacture, or to have manufactured by a Third Party, the Active
Ingredient or the Product, as applicable. In such case: (i) the intended manufacturer will be deemed to have granted the Party providing such notice with a supplemental, royalty-free, worldwide, non-exclusive license to use its Background IP
solely to the extent necessary to conduct such manufacture (subject in the case of the BIOLEX Background Patents to federal legal requirements for manufacturing to the extent applicable under BIOLEX’s License Agreement with North Carolina State
University); and (ii) the intended manufacturer will promptly provide such Party (or its designee), with all specifications, know-how, trade secrets, software, and other items (including all specialized items, including tooling, molds, etc.),
information and training reasonably necessary for the manufacture of the Product; provided, however, that if the intended recipient of the technology transfer is a Competitor of the intended manufacturer, this transfer is conditioned upon
implementation by the intended manufacturer and the Competitor of mutually acceptable procedures to protect the intended manufacturer’s proprietary information from misappropriation by the Competitor; and (iii) the actual manufacturing
Party shall be entitled to reimbursement for all commercially reasonable Third Party costs related to the manufacture and supply of the Active Ingredient or Product, as applicable, prior to any allocation of Third Party proceeds under
Section 6.5.1. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 13 

	 	6.3.3	Subcontractors. Neither Party may subcontract any of its retained manufacturing rights under this Section 6.3 to an Affiliate or Third Party without first having agreed
in writing with the other Party on how the costs of such subcontracting activities shall be calculated and whether such costs may be included as Manufacturing Costs under Annex 3. A Party seeking to subcontract any retained manufacturing
rights under this Section 6.3 shall furnish the other Party with advanced written notice thereof, which notice shall specify the work to be subcontracted, and shall obtain a written undertaking from the subcontractor that it shall be subject to
the applicable terms and conditions of this Agreement. 

  

	6.4	Separate Agreements. The conditions and terms of a collaboration with any Third Party shall be negotiated and agreed upon in a separate license and/or development agreement
between the Third Party on one hand, and BIOLEX together with OCTOPLUS on the other hand, and such agreement must be acceptable to both Parties; provided, however that if a Party has stepped out of further development and the other Party has stepped
in, in each case as described in Section 5.3, the Party that has stepped out shall have no rights with respect to negotiating or entering into such separate license and/or development agreement, which shall be negotiated and entered into by the
Third Party and the Party that has stepped in, subject to the profit sharing arrangements specified in Section 6.5. 

  

	6.5	Revenue Sharing from Commercialization Program. 

  

	 	6.5.1	Any license fees, up-front payments, milestone payments, royalty payments, or similar payments received with respect to Product shall be shared equally, except as set forth in
Article 5 with respect to the profit share of a Party that has stepped out with respect to such Product, and as set forth in Section 7.1.4 with respect to payments related to freedom to operate with respect to certain Background IP.

  

	 	6.5.2	OCTOPLUS or BIOLEX shall be entitled to retain any Third Party payment received pursuant to a license and/or development agreement that is intended to pay such Party for
manufacturing or supply of the Active Ingredient or Product; provided, however, that any Manufacturing Profits associated with providing the Product or Active Ingredient, as applicable, as determined according to Annex 3, shall be shared
according to Section 6.5.1. 

  

	 	6.5.3	OCTOPLUS or BIOLEX shall be entitled to retain any Third Party payment received pursuant to a license and/or development agreement that is intended to pay such Party for
non-manufacturing services provided to or on behalf of the Third Party with respect to Commercialization of the Product; provided, however, that any profits associated with providing such services (determined by the Steering Committee in a manner
consistent with the calculation of Manufacturing Profits in Annex 3, as applicable, and including the same margin) shall be shared according to Section 6.5.1. 

  

	 	6.5.4	Any payments due from one Party to the other Party under this Section 6.5 shall be promptly remitted (and in any case within fifteen (15) days after receipt by the
remitting Party of the corresponding payment from the Third Party giving rise to the payment obligation) to the other Party, without right of setoff against any amount due from the other Party to the remitting Party hereunder or pursuant to any
other agreement between the Parties. 

  

	6.6	 Acquisition by Competitor. If one of the Parties (the “Acquired Party”) is or enters into any agreement to be Acquired (as defined below) at
any time during the Term by a competitor of the other Party (the “Competitor”, as defined below), the Acquired Party shall provide prompt notice of such Acquisition or agreement to be Acquired to the other Party. The Steering
Committee promptly shall meet prior to the closing of such Acquisition, upon request of the non-acquired Party, to identify and implement changes to the Primary Development Program and/or Commercialization Program designed to shield the other

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 14 

	 	 
Party’s Confidential Information from disclosure to the Competitor, including without limitation consideration of the use of Drug Master File
(“DMF”) procedures in connection with development of Product or placing the DMF into escrow with an independent entity or person acceptable to both Parties acting in confidence, and requiring the Acquired Party to promptly return to the
other Party any of the other Party’s Confidential Information that would no longer be needed by the Acquired Party in consequence of the changes directed by the Steering Committee. For purposes of this Section, a Party is
“Acquired” if another person or entity through an acquisition transaction controls, acquires, purchases, or merges with, such Party, whether by stock purchase, stock exchange, merger, consolidation, purchase of assets, joint
venture, partnership, or otherwise. 

  

	 	6.6.1	In case of OCTOPLUS, Competitors are companies active in development of controlled release formulations for parenteral applications. 

  

	 	6.6.2	In case of BIOLEX, Competitors are companies active in development of protein therapeutics based on recombinant expression systems. 

 7. INTELLECTUAL PROPERTY 
  

	7.1	Licenses to Intellectual Property. 

  

	 	7.1.1	Subject to the terms of this Agreement, BIOLEX hereby grants OCTOPLUS a worldwide, non-exclusive, irrevocable license to use BIOLEX Background IP and Joint Invention Patents solely
to the extent necessary for performance of its rights and obligations under this Agreement, and, if BIOLEX has stepped out and OCTOPLUS has stepped in pursuant to Section 5.3, for sublicensing to one or more Third Parties solely for
Commercialization of Product according to Article 6. This license may not be transferred or sublicensed except to the extent necessary or useful in any such Commercialization of Product. 

  

	 	7.1.2	Subject to the terms of this Agreement, OCTOPLUS hereby grants BIOLEX a worldwide, non-exclusive, irrevocable license to use OCTOPLUS Background IP and Joint Invention Patents
solely to the extent necessary for performance of its rights and obligations under this Agreement, and, if OCTOPLUS has stepped out and BIOLEX has stepped in pursuant to Section 5.3, for sublicensing to one or more Third Parties solely for
Commercialization of Product according to Article 6. This license may not be transferred or sublicensed except to the extent necessary or useful in any such Commercialization of Product. 

  

	 	7.1.3	Ownership of existing inventions and know-how of either Party or future inventions and know-how of either Party made outside the scope of this Agreement shall remain in the sole
possession of the contributing Party. Any desired licenses or sublicenses to Intellectual Property rights of either Party outside the arrangement of this Agreement will be subject to separate, additional negotiations and agreements, but neither
Party is obligated to enter into such negotiations or agreements. 

  

	 	7.1.4	 Each Party shall use its Commercially Reasonable Efforts to secure the freedom to operate with its respective Background IP that is in existence on the Effective
Date and directly shall pay all costs, including but not limited to license fees, royalties and any other payments, associated therewith. In this sense freedom to operate shall mean the ability to use Background Patents and Background Know-How that
are in existence on the Effective Date to the extent necessary in connection with the Preliminary Development Program, the Primary Development Program or the Commercialization Program, without infringement of Third Party patents. To the extent that
one Party incurs any 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 15 

	 	 
commercially reasonable expense to secure freedom to operate with respect to the other Party’s Background IP that is the other Party’s
responsibility under this Section 7.1.4, such expense shall be offset against the other Party’s share of Third Party proceeds that would otherwise be payable under Section 6.5.1 and Annex 3. 

  

	 	7.1.5	Except as set forth in Section 7.1.4, all costs (including but not limited to license fees, royalties and any other payments) incurred to procure freedom to operate relative to
the Product, including without limitation with respect to Background IP of a Party that is Developed after the Effective Date, will constitute Third Party costs of the Primary Development Program pursuant to Section 5.2.1 and all corresponding
provisions under this Agreement, including without limitation those concerning consequences of one Party or the other stepping out following the Preliminary Development Program. 

  

	7.2	Classification of New Inventions. Each Party shall promptly disclose to the other Party each and every invention, whether or not patentable, that is conceived, reduced to
practice, and/or otherwise developed under the scope of this Agreement (collectively, “Developed”). 

  

	 	7.2.1	Any and all inventions (including all results and know-how) Developed solely or jointly under this Agreement shall be deemed a BIOLEX sole invention to the extent it relates solely
to BIOLEX’s LEX SystemTM or its Active Ingredient, and shall be owned solely by BIOLEX along with all related Intellectual Property rights. 

  

	 	7.2.2	Any and all inventions (including all results and know-how) Developed solely or jointly under this Agreement shall be deemed an OCTOPLUS sole invention to the extent it relates
solely to the OCTOPLUS Technology, and shall be owned solely by OCTOPLUS along with all related Intellectual Property rights. 

  

	 	7.2.3	All other inventions (including all results and know-how) that are not related to either BIOLEX’s LEX SystemTM or its Active Ingredient or the OCTOPLUS Technology that are
Developed solely by a Party under this Agreement shall be deemed a Sole Invention of the Party whose employees or consultants Developed such invention, and shall be owned solely by such Party along with all related Intellectual Property rights. The
inventions of a Party described in this Section 7.2.3, together with such Party’s inventions described in Section 7.2.1 or Section 7.2.2, as the case may be, are referred to herein as “BIOLEX Sole Inventions” or
“OCTOPLUS Sole Inventions”, respectively. 

  

	 	7.2.4	All other inventions (including all results and know-how) Developed jointly under this Agreement shall be deemed a Joint Invention, and shall be owned jointly by the Parties along
with all related Intellectual Property rights (“Joint Inventions”). 

  

	 	7.2.5	In order to effectuate the intent of this Section 7.2, the Parties hereby agree to (i) execute, and to cause their officers, employees, contractors, and agents to execute,
any and all such documents, including, without limitation, assignments of inventions and discoveries and all related Intellectual Property rights and (ii) engage in such other activities as reasonably requested by the other Party at such other
Party’s expense for purposes of vesting ownership of inventions and related Intellectual Property rights in accordance with the provisions hereof. 

  

	7.3	Sole Inventions. Each Party may file and own patents and patent applications covering its Sole Inventions under Article 7 and any compensation to an inventor under provisions
of labor law shall be paid by the employer of that inventor. 

  

	7.4	 Joint Inventions. Patent applications on Joint Inventions may be filed only if the Parties agree to file jointly on them. If the Parties agree to file for
and obtain patents on Joint Inventions, all expenses incurred therein shall be shared equally, except 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 16 

	 	 
that the employer of each inventor – if applicable – will pay the inventor’s compensation. If a patent is obtained on a Joint Invention, no
Party shall transfer its interest in such patent to a Third Party unless both Parties agree to do so. Notwithstanding the foregoing the Parties shall be entitled to transfer their respective rights to their respective Affiliates and successors in
interest as set forth in Section 11.16 hereof. 

  

	7.5	Use of Joint Inventions. Subject to the exclusivity arrangements and other limitations specified in this Agreement, each Party is free to use and sublicense Joint Inventions
to Third Parties without any further obligations or accounting to the other Party except those required in connection with use of the other Party’s Background IP and/or Sole Inventions. 

  

	7.6	Certain Matters Relating to Acquisitions. In the event of a permitted assignment of this Agreement by either Party to a Third Party, or a transaction in which a Third Party
becomes an Affiliate of a Party, the definition of BIOLEX Background IP or OCTOPLUS Background IP, as the case may be, will not include any Intellectual Property or subject matter that, prior to such transaction, was Controlled by such Third Party,
and the other Party to this Agreement will have no right or license under this Agreement to any such Third Party Intellectual Property or subject matter. 

  

	7.7.	Patent Infringement of/by Background Patents. Each Party shall promptly notify the other Party upon learning of any infringement or misappropriation by a Third Party of the
other Party’s or its own Background IP or upon learning that the Parties’ activities under this Agreement allegedly infringe or misappropriate a Third Party’s rights. Each Party will then cooperate with the other Party in determining
the course of action to pursue to stop such infringement or misappropriation of such Third Party or to respond to such Third Party’s alleged infringement claim, as the case may be. The Party that owns or Controls the Background IP (the
“Owning Party”) that is allegedly infringing or infringed shall have the sole right, but not the obligation, to bring, defend, and maintain any appropriate suit or action against, or to control the conduct of, such Third Party,
except that if the Owning Party has stepped out as described in Section 5.3, the Party that has stepped in also shall have the right to bring, defend, and maintain any appropriate suit or action against, or to control the conduct of, such Third
Party, solely to the extent that the alleged infringement relates to the Product. If the Owning Party declines to bring, defend, and maintain any appropriate suit or action against, or to control the conduct of, such Third Party, then upon consent
of the Owning Party, the other Party may bring, defend, and maintain any appropriate suit or action against, or take action to control the conduct of, such Third Party with respect to the Background IP, and the Owning Party shall provide reasonable
cooperation to the other Party in connection therewith. If the Party bringing or defending a suit or action requests the other Party to join in such suit or action, the other Party shall execute all papers, perform such other acts as may be
reasonably required, and provide all reasonable assistance requested in doing so. Costs and expenses incurred in connection with bringing, defending, or maintaining any appropriate suit or action against, or controlling the conduct of, any Third
Party with respect to freedom to operate shall be (i) the sole responsibility of the Owning Party if related to Background IP in existence on the Effective Date and shall be handled as described in Section 7.1.4, and (ii) if unrelated
to Background IP in existence on the Effective Date, shall be treated as a shared Third Party cost as described in Section 7.1.5. All recoveries from Third Parties in connection therewith shall be credited to the Party(ies) that would bear the
expense of securing freedom to operate with respect to the Background IP giving rise to such recoveries under Section 7.1.4 or Section 7.1.5, as applicable. 

  

	7.8	 Patent Infringement of/by Joint Invention Patents. Each Party shall promptly notify the other Party upon learning of any infringement by a Third Party of any
patent claiming a Joint Invention (“Joint Invention Patent”) or a claim of alleged infringement of Third Party rights arising out of either Party practicing a Joint Invention or Joint Invention Patent. Each 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 17 

	 	 
Party will then cooperate with the other in determining the course of action (e.g., jointly selecting a suitable patent counsel) necessary to stop the
infringement related to any Joint Invention Patent or Joint Invention, and the Parties shall equally share all costs and expenses related thereto; provided, however, that if any Party makes use of a Joint Invention or Joint Invention Patent outside
the scope of this Agreement, such Party shall be solely responsible for the costs and expenses related to any litigation or other actions to stop such alleged infringement of Third Party rights and shall indemnify and hold harmless the other Party.

  

	7.9	Recovery for Patent Infringement. Any monetary recovery arising from claims brought under Section 7.8 in connection with use of a Joint Invention or Joint Invention
Patent inside the scope of this Agreement shall first be applied to paying all costs and expenses associated with the prosecution of such claims (including attorney’s fees) and then any remaining amounts (and any non-monetary recovery) shall be
treated as sublicense revenues and shall be divided between the Parties as if such amounts were profits from sales of Product. 

 8. CONFIDENTIALITY 
  

	8.1	Confidentiality of Information. No Party to this Agreement shall disclose to any Third Party nor use for any purpose, other than the purpose of this Agreement, information or
data received from a Party under this Agreement, without prior written approval from the Party from whom the information or data was received. 

  

	8.2	Exceptions. The obligations of non-disclosure and non-use shall apply for a period of ten (10) years following the expiration or termination of this Agreement, but shall
not apply to any information or data which receiving Party can show by competent proof that it: 

  

	 	8.2.1	is known to the public prior to disclosure hereunder; 

  

	 	8.2.2	becomes known to the public through no fault of the receiving Party; 

  

	 	8.2.3	was known to the receiving Party prior to disclosure under this Agreement; 

  

	 	8.2.4	is disclosed to the receiving Party by a Third Party having a legal right to make such disclosure; 

  

	 	8.2.5	is reasonably required to be disclosed to further the purposes of this Agreement, including to file for registration, to file patent applications, and to contract with Third Parties
under an obligation of confidentiality to further the development of the Products; or 

  

	 	8.2.6	is required to be disclosed to a regulatory agency of competent jurisdiction consistent with the receiving Party’s past practice, provided that if such agency is not required
by law to maintain the confidentiality of such information, then the disclosing Party shall first be given the opportunity to intervene and contest the disclosure or seek appropriate protection. 

  

	8.3	 Publications. Neither Party may present or publish research results arising from activities contemplated by this Agreement in a thesis, scientific
publication, conference, or otherwise without the prior written consent of the other Party. Presentations or publications will be presented in writing in the English language and will be presented to the other Party for review and comment at least
forty-five (45) days prior to the time which the presentation or publication is proposed for submission to any Third Party. Within thirty (30) days after its receipt of such presentation or publication and at least one week prior to the
time which the presentation or publication is proposed for submission to any Third Party, the other Party will provide notice 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 18 

	 	 
whether it has any comments or objection to the proposed presentation or publication. The submitting Party will consider in good faith all comments by the
reviewing Party. If a reasonable objection is raised, including, for example, that the contents of the presentation or publication contain patentable subject matter for which patent protection should be sought, or that the presentation or
publication discloses Confidential Information of the other Party, then submission of the presentation or publication will be delayed, unless and until such time as consent to submission of the presentation or publication is given, such consent not
to be unreasonably withheld. Each Party may be acknowledged on any publication or presentation by the other Party in accordance with generally accepted rules of authorship. 

  

	8.4	Publicity. 

  

	 	8.4.1	Press Release. Any proposed publicity, press release or other announcements by a Party relating to this Agreement will be reviewed in advance by, and will be subject to the
approval of, the other Party, such approval not to be unreasonably withheld or delayed. Upon execution of this Agreement, the Parties agree to issue a mutually acceptable joint press release announcing the collaboration set forth herein.

  

	 	8.4.2	Terms of the Agreement. Neither Party will make any public announcement concerning the existence of or the terms of this Agreement, without the prior written approval of the
other Party with regard to the form, content and precise timing of such announcement, except such as may be required to be made by either Party in order to comply with applicable law, regulations, court or administrative order, or tax filings. Such
consent will not be unreasonably withheld or delayed by such other Party. Notwithstanding anything to the contrary in this Agreement, either Party may make a disclosure of the existence and terms of this Agreement to its attorneys, advisers,
investors, prospective investors, potential acquirers, lenders and other financing sources, as the case may be, under circumstances that reasonably ensure the confidentiality thereof. Notwithstanding anything to the contrary in this Agreement,
nothing in this Section 8.4 is intended to prohibit either Party from republishing or restating information relating to this Agreement that has already been approved by the other Party for use in a prior press release or public announcement.
Such information may be republished or restated in substantially the same content and form as already approved by the other Party. 

  

	 	8.4.3	Use of Other Party Name or Logo. Except to the extent required to comply with the law or a court or administrative order, neither Party will use the name or logo of the other
Party without its written consent. 

 9. WARRANTIES AND LIABILITY 
  

	9.1	Mutual Representations and Warranties. Each of the Parties hereby represents and warrants to the other Party as follows: 

  

	 	9.1.1	This Agreement has been duly executed and delivered and is a legal and valid obligation binding upon such Party and enforceable in accordance with its terms.

  

	 	9.1.2	Delivery and performance of the Agreement by such Party does not conflict with any agreement, instrument or understanding, oral or written, to which it is a Party or by which it is
bound, nor violate any law or regulation of any court, governmental body or administrative or other agency having jurisdiction over it. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 19 

	 	9.1.3	It has the full power and authority to enter into this Agreement and to carry out the obligations contemplated hereby. 

  

	 	9.1.4	It has taken all necessary corporate action on its part to authorize the execution and delivery of this Agreement. 

  

	 	9.1.5	It and its Affiliates require all of their respective employees and consultants to enter into agreements that provide, among other things, that if they become the inventor of a
patentable invention in the course of their work on behalf of such entity, they will assign their rights with respect to such invention to such entity or as otherwise directed by such entity (unless such persons are already bound by a written
contract with terms and conditions no less restrictive than described in this Section 9.1.5). 

  

	9.2	OCTOPLUS Warranties. Except as separately disclosed by OCTOPLUS to BIOLEX prior to the Effective Date, OCTOPLUS represents and warrants to BIOLEX that:

  

	 	9.2.1	As of the Effective Date OCTOPLUS has the right to perform its obligations under the Agreement and contribute the OCTOPLUS Background IP to the performance hereunder as specified
herein without actual knowledge of violating the Intellectual Property rights or other rights of any Third Party. OCTOPLUS owns all right, title and interest in and to, or otherwise Controls, the OCTOPLUS Background IP and will continue to do so at
all times throughout the Term. 

  

	 	9.2.2	To the actual knowledge of OCTOPLUS, the issued claims in the OCTOPLUS Background Patents as of the Effective Date are valid and enforceable. 

  

	 	9.2.3	OCTOPLUS has not, and during the Term will not, grant any right to any Third Party relating to the OCTOPLUS Background IP in a manner, or pursue any other activity, that would
otherwise conflict with the rights granted to BIOLEX hereunder. 

  

	 	9.2.4	To the actual knowledge of OCTOPLUS, as of the Effective Date, (i) there is no Third Party infringing any of the OCTOPLUS Background Patents or misappropriating or using
OCTOPLUS Background Know-How, (ii) the OCTOPLUS Background IP, as applied to the Product, does not infringe any Third Party Intellectual Property rights, and (iii) there is no circumstance or development that is reasonably likely to impair
materially the Commercialization of the Product. 

  

	 	9.2.5	As of the Effective Date, OCTOPLUS has not been served with any interference action or litigation with respect to the OCTOPLUS Background Patents, and OCTOPLUS has not received any
written communication that expressly threatens interference actions or other litigation before any patent office, court, or any other governmental entity in any jurisdiction in regard to the OCTOPLUS Background Patents. 

  

	 	9.2.6	Without limiting the generality of the foregoing, OCTOPLUS represents and warrants that, as of the time of release of Product to BIOLEX in accordance with Section 5.1 of this
Agreement, all Product released (a) will conform to the applicable Specifications, and (b) will have been manufactured in accordance with GMP (if applicable) and all applicable laws and regulations and in accordance with the applicable
certificates of analysis. 

  

	 	9.2.7	Without limiting the generality of the foregoing, OCTOPLUS represents and warrants that it has the right to provide to BIOLEX the Product (other than the Active Ingredient) and
information provided by OCTOPLUS hereunder, and to grant BIOLEX the right to use such Product and information for the conduct of BIOLEX’s rights and obligations hereunder. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 20 

	 	9.2.8	OCTOPLUS is a wholly-owned subsidiary of OctoShare B.V. OCTOPLUS has the absolute and unrestricted right, power and authority to execute and deliver this Agreement and to perform
its obligations under this Agreement, and such action has been duly authorized by all necessary action by OctoShare B.V., OCTOPLUS, and any other of their various Affiliates. 

  

	9.3	BIOLEX Warranties. Except as separately disclosed by BIOLEX to OCTOPLUS prior to the Effective Date, BIOLEX represents and warrants to OCTOPLUS that:

  

	 	9.3.1	As of the Effective Date BIOLEX has the right to perform its obligations under the Agreement and contribute the BIOLEX Background IP to the performance hereunder as specified herein
without actual knowledge of violating the Intellectual Property rights or other rights of any Third Party. BIOLEX owns all right, title, and interest in and to, or otherwise Controls, the BIOLEX Background IP and will continue to do so at all times
throughout the Term. 

  

	 	9.3.2	To the actual knowledge of BIOLEX, the issued claims in the BIOLEX Background Patents as of the Effective Date are valid and enforceable. 

  

	 	9.3.3	BIOLEX has not, and during the Term will not, grant any right to any Third Party relating to the BIOLEX Background IP in a manner, or pursue any other activity, that would otherwise
conflict with the rights granted to OCTOPLUS hereunder. 

  

	 	9.3.4	To the actual knowledge of BIOLEX, as of the Effective Date, (i) there is no Third Party infringing any of the BIOLEX Background Patents or misappropriating or using BIOLEX
Background Know-How, (ii) the BIOLEX Background IP, as applied to the Product, does not infringe any Third Party Intellectual Property rights, and (iii) there is no circumstance or development that is reasonably likely to impair materially
the Commercialization of the Product. 

  

	 	9.3.5	As of the Effective Date, BIOLEX has not been served with any interference action or litigation with respect to the BIOLEX Background Patents, and BIOLEX has not received any
written communication that expressly threatens interference actions or other litigation before any patent office, court, or any other governmental entity in any jurisdiction in regard to the BIOLEX Background Patents. 

  

	 	9.3.6	Without limiting the generality of the foregoing, BIOLEX represents and warrants that it has the right to provide to OCTOPLUS the Active Ingredient and information provided by
BIOLEX hereunder, and to grant to OCTOPLUS the right to use such Active Ingredient and information for the conduct of OCTOPLUS ́s rights and obligations hereunder. 

  

	 	9.3.7	BIOLEX further warrants that the Active Ingredient and other materials provided to OCTOPLUS hereunder (a) will conform to their applicable Specifications and (b) will have
been manufactured in accordance with GMP (if applicable) and all applicable laws and regulations and in accordance with the applicable certificates of analysis. 

  

	9.4	Indemnification by OCTOPLUS. OCTOPLUS agrees to indemnify and hold harmless BIOLEX for any losses, costs, damages, liabilities and expenses (including reasonable attorney
fees and court costs) (collectively “Damages”) which arise out of, relate to or result from any claim, lawsuit or other action by a Third Party to the extent such Damages arise out of, relate to or result from

  

	 	a.	the PolyActiveTM aspects of Product, 

  

	 	b.	Product released not according to the agreed Specifications, 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 21 

	 	c.	the material breach by OCTOPLUS of any of its representations, warranties, covenants or obligations contained within this Agreement, or 

  

	 	d.	OCTOPLUS’s willful misconduct, gross negligence or knowing violation of laws with regard to the Product, the Active Ingredient, or activities conducted under or otherwise in
connection with this Agreement or the Feasibility Agreement, 

  

	    	except to the extent, if any, that such Damages are caused by, or arise from or relate to BIOLEX’s gross negligence, willful misconduct or breach of this Agreement, as to which
BIOLEX shall indemnify, hold harmless, and defend OCTOPLUS, as set forth in Section 9.5. 

  

	9.5	Indemnification by BIOLEX. BIOLEX agrees to indemnify and hold harmless OCTOPLUS for any Damages which arise out of, relate to or result from any claim, lawsuit or other
action by a Third Party to the extent such Damages arise out of, relate to or result from 

  

	 	a.	the LEX SystemTM aspects of Product, 

  

	 	b.	Active Ingredient supplies provided by BIOLEX hereunder released not according to the agreed Specifications, 

  

	 	c.	the material breach by BIOLEX of any of its representations, warranties, covenants or obligations contained within this Agreement, or 

  

	 	d.	BIOLEX’s willful misconduct, gross negligence or knowing violation of laws with regard to the Product, the Active Ingredient, or activities conducted under or otherwise in
connection with this Agreement or the Feasibility Agreement, 

  

	    	except to the extent, if any, that such Damages are caused by, or arise from or relate to OCTOPLUS’s gross negligence, willful misconduct or breach of this Agreement, as to
which OCTOPLUS shall indemnify, hold harmless, and defend BIOLEX, as set forth in Section 9.4. 

  

	9.6	Patent Infringements. With respect to each Party’s Background IP in existence on the Effective Date and contributed and used in connection with the activities conducted
under this Agreement, the contributing Party agrees to indemnify and hold harmless the other Party for any Damages arising out of any claims, suits, or proceedings alleging facts on infringements of Third Party patents by such contributed Background
IP. 

  

	9.7	Limitation of Liability. 

  

	 	9.7.1	Any indemnification by OCTOPLUS under Section 9.4(b) and by BIOLEX under Section 9.5(b) shall not exceed its liability insurance coverage (which in any case shall be in an
insured amount not less than the amount required under Section 9.7.2). 

  

	 	9.7.2	Both Parties agree to maintain during the Term insurance of the types and in the insured amounts listed in the insurance cover sheets of each Party as attached hereto as Annex
4. 

  

	 	9.7.3	 IN NO EVENT WILL EITHER PARTY, ITS AFFILIATES, OR ITS OR THEIR RESPECTIVE DIRECTORS, OFFICERS, EMPLOYEES, AGENTS, SUCCESSORS OR ASSIGNS, BE LIABLE TO THE OTHER FOR
ANY SPECIAL, INCIDENTAL, PUNITIVE OR CONSEQUENTIAL DAMAGES ARISING IN CONNECTION WITH THIS AGREEMENT, WHETHER BASED ON BREACH OF CONTRACT, NEGLIGENCE, OR OTHERWISE, AND WHETHER OR NOT SUCH PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
THE LIMITATIONS SET FORTH ABOVE SHALL BE DEEMED TO APPLY TO THE MAXIMUM EXTENT 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 22 

	 	 
PERMITTED BY APPLICABLE LAW AND NOTWITHSTANDING THE FAILURE OF THE ESSENTIAL PURPOSE OF ANY LIMITED REMEDIES. THE PARTIES ACKNOWLEDGE AND AGREE THAT THEY
HAVE FULLY CONSIDERED THE FOREGOING ALLOCATION OF RISK AND FIND IT REASONABLE, AND THAT THE FOREGOING LIMITATIONS ARE AN ESSENTIAL BASIS OF THE BARGAIN BETWEEN THE PARTIES. 

 10. TERMINATION 
  

	10.1	Term. This Agreement shall be effective as of the Effective Date and shall continue in full force and effect until the termination or expiration of all Third Party licenses
entered into under the Commercialization Program or until earlier terminated in accordance with this Article 10 (the “Term”). 

  

	10.2	Termination for Breach. If either Party materially breaches this Agreement and fails to cure such breach within forty-five (45) days following its receipt of written
notice thereof from the non-breaching Party, the non-breaching Party may terminate this Agreement by subsequent written notice to the breaching Party. The breaching Party shall make available to the other Party within the aforementioned forty-five
(45) day period all information regarding Joint Inventions and experimental data and results generated by each of the Parties under this Agreement. Without limiting any remedy otherwise available to the non-breaching Party, at the non-breaching
Party’s election, to be exercised by written notice delivered no later than thirty (30) days after the cure period has elapsed, the breaching Party shall be deemed to have stepped out and the non-breaching Party to have stepped in for all
purposes pursuant to Article 5. 

  

	10.3	Termination for Other Reason. Either Party hereto may terminate this Agreement upon sixty (60) days written notice to the other Party: (a) if both Parties have
stepped out as described in Section 5.3.3; or (b) if the Parties have not been successful in attracting a Third Party for Commercialization of Product within thirty (30) months following completion of the Primary Development Program.
In that case, (i) the Parties shall cease all activities hereunder, and (ii) each Party may make use of all Joint Inventions without further obligations or accounting to the other Party; provided, however, that neither Party shall have any
licenses or rights to the Intellectual Property of the other Party following such termination except as described in Section 7.5 or as separately agreed by the Parties. 

  

	10.4	Termination for Insolvency Events. This Agreement may be terminated, prior to the expiration of its term, upon fifteen (15) days written notice by either Party:
(i) in the event that the other Party hereto shall (1) file a petition seeking to take advantage of any law relating to bankruptcy, insolvency, reorganization, winding-up, or composition or readjustment of debts (the “Bankruptcy
Laws”), (2) apply for or consent to the appointment of, or the taking of possession by, a receiver, custodian, trustee or liquidator of itself or of all or a substantial part of its property, (3) make a general assignment for the
benefit of its creditors, (4) be declared bankrupt, (5) fail to controvert in a timely and appropriate manner, or acquiesce in writing to, any petition filed against it in any involuntary case, or (6) take any corporate action for the
purpose of effecting any of the foregoing; or (ii) if a proceeding or case shall be commenced against the other Party hereto in any court of competent jurisdiction, seeking (1) its liquidation, reorganization, dissolution or winding-up, or
the composition or readjustment of its debts, (2) the appointment of a trustee, receiver, custodian, liquidator or the like of the Party or of all or any substantial part of its assets, or (3) similar relief under any Bankruptcy Law, or an
order, judgment or decree approving any of the foregoing shall be entered and continue unstayed for a period of sixty (60) days; or an order for relief against the other Party hereto shall be entered in an involuntary case under the Bankruptcy
Laws. The effect of termination under this clause shall be the same as under Section 10.3. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 23 

	10.5	Surviving Rights and Obligations. 

  

	 	10.5.1	Termination or expiration of this Agreement for any reason shall not deprive a Party of any of its rights that shall have accrued to the benefit of such Party prior to such
termination or expiration. 

  

	 	10.5.2	Such termination or expiration shall not relieve a Party from obligations that are expressly indicated to survive the termination or expiration of this Agreement. In addition,
termination of this Agreement shall not relieve the Parties of their obligations and rights with regard to, patent infringements and use of licenses, confidentiality, warranties and liability, records, audit rights, indemnification, post-termination
rights and dispute resolutions hereunder. 

 11. MISCELLANEOUS 
  

	11.1	No Guarantee. The Parties acknowledge that there can be no guarantee that Products will within a certain time period be successfully Developed with regard to fitness for a
particular use, feasibility of manufacturing, marketability and all technical, legal and commercial aspects connected thereto nor that Third Party collaborations can be established to further develop the Products. 

  

	11.2	Force Majeure. Neither Party shall be responsible or liable to the other Party for any failure to perform any of its obligations hereunder, if such failure results from
circumstances beyond the control of such Party, including, without limitation, requisition by any government authority, the effect of any statute, ordinance or governmental order or regulation, wars, terrorism, crime, strikes, lockouts, riots,
epidemic, disease, an act of God, civil commotion, fire, earthquake, storm, failure of public utilities, common carriers or supplies, or any other circumstances, whether or not similar to the above causes and whether or not foreseeable. In the event
of any such force majeure, the Party affected will promptly notify the other Party, will use Commercially Reasonable Efforts to overcome such force majeure, and will keep the other Party informed with respect thereto. If one of the Parties cannot
comply with this Agreement due to an event of force majeure, which continues for more than sixty (60) days, then the other Party may terminate this Agreement. No Party shall have any liability to the other related to termination costs as a
result of force majeure. 

  

	11.3	Notices. Any notice required or permitted to be given under this Agreement shall be in writing and shall be deemed to have been sufficiently given for all purposes
(i) when received, if delivered personally or sent by facsimile transmission with confirmed receipt, or (ii) two business days after the date mailed by first class mail or one business day after the date sent by an internationally
recognized overnight delivery service with charges prepaid. Unless otherwise specified in writing, the mailing addresses and facsimile number of the Parties for notices shall be as follows: 

  

					
	If to BIOLEX:	  		  	BIOLEX, Inc.
		  		  	Attn: President
		  		  	158 Credle Street
		  		  	Pittsboro, NC 27312
		  		  	Fax: 919.542.9910
			
	If to OCTOPLUS:	  		  	OCTOPLUS Technologies B.V.
		  		  	Attn: Managing Director
		  		  	Zernikedreef 12, 2333 CL Leiden
		  		  	The Netherlands
		  		  	Fax: +31.71.524.4043

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 24 

	11.4	Titles. The titles of the Articles and Sections of this Agreement are for general information and reference only, and this Agreement shall not be construed by reference to
the titles. 

  

	11.5	Severability. If any provision of this Agreement or the application thereof is adjudicated to be invalid or unenforceable, such invalidity or unenforceability shall not
affect other provisions or applications of this Agreement that can be given effect without the invalid and unenforceable provision or application, and to this end, the provisions or applications of this Agreement shall be severable. Should any
problems in this regard occur or be threatened, the Parties will inform each other as soon as practical and renegotiate the relevant provision in good faith but in any event neither Party shall be obligated to abide by any exclusivity term that is
in breach of such applicable law. 

  

	11.6	Choice of Law. This Agreement shall be construed and the rights of the Parties determined in accordance with the laws of Switzerland regardless of the laws that might
otherwise govern under applicable conflict of laws principles thereof. 

  

	11.7	Settlement of Disputes. The Steering Committee shall attempt to amicably resolve any dispute concerning any rights or obligations of either Party under this Agreement. If the
Steering Committee is unable to resolve any such dispute, the matter shall be referred to the President of OCTOPLUS and the President of BIOLEX for resolution by delivering a written notice to that effect to the other Party. Thereafter, the
Presidents shall meet, either in person or telephonically, to negotiate in good faith a mutually acceptable resolution to the dispute. If the Parties’ respective Presidents cannot reach agreement within two (2) weeks following the date of
written notice, then either Party may initiate arbitration as described in Section 11.8. 

  

	11.8	Binding Arbitration. The Parties agree that any claim or dispute between them or against any agent, employee, successor, or assign of the other, whether related to this
Agreement or otherwise, and any claim or dispute related to this agreement or the relationship or duties contemplated under this contract, including the validity of this arbitration clause but excluding any deadlock addressed in Section 3.6,
shall be resolved by binding arbitration in accordance with the Commercial Arbitration Rules of the International Chamber of Commerce (ICC) as in effect at the time of the arbitration hearing. The arbitration panel will be composed of three
arbitrators, one of whom will be chosen by BIOLEX, one by OCTOPLUS, and the third by the two so chosen. If both or either of BIOLEX or OCTOPLUS fails to choose an arbitrator or arbitrators within fourteen (14) days after receiving notice of
commencement of arbitration, or if the two arbitrators fail to choose a third arbitrator within fourteen (14) days after their appointment, the ICC shall, upon the request of both or either of the parties to the arbitration, appoint the
arbitrator or arbitrators required to complete the panel. The arbitrators shall render a written opinion containing the reasons for the panel’s decision. The decision of the arbitrators shall be final and binding on the parties, and specific
performance may be ordered by any court of competent jurisdiction. Except as otherwise agreed by the Parties, the arbitration shall be conducted in New York, New York, U.S.A. in the English language. Each Party will bear its own costs in preparing
for and participating in the resolution of any dispute under this Section 11.8, and the costs of arbitrators shall be equally divided between the Parties, unless the arbitrators find that the losing Party’s claims either substantially
lacked merit or were asserted in bad faith, in which case, the arbitrators may require such Party to bear the cost of the arbitration and reasonable costs and expenses of defense of the winning Party. Any award of the arbitrator(s) may be entered as
a judgment in any court having jurisdiction. 

  

	11.9	No Jury Trial. In the event that any dispute or claim of any sort arising out of this Agreement or any subsequent agreement concerning the subject matter and/or any dispute
or claim concerning competent court and/or jurisdiction and/or execution of any award granted by a foreign court or arbitration panel should be filed, each of the Parties waives irrevocably any right that such Party may have to demand or request a
trial by jury. 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 25 

	11.10	Equitable Relief. Each Party acknowledges and agrees that the restrictions set forth in Section 2.2 and Articles 7 and 8 of this Agreement are reasonable and necessary
to protect the legitimate interests of the other Party and that such other Party would not have entered into this Agreement in the absence of such restrictions, and that any violation of any provision of Section 2.2 or Article 7 or 8 will
result in irreparable injury to such other Party. Each Party also acknowledges and agrees that in the event of a violation or threatened violation of any provision of Section 2.2 or Articles 7 or 8, the other Party shall be entitled to seek
preliminary injunctive relief in any applicable court, without the necessity of proving irreparable injury or actual damages and without the necessity of having to post a bond, as well as an equitable accounting of all earnings, profits and other
benefits arising from any such violation. The rights provided in the immediately preceding sentence shall be cumulative and in addition to any other rights or remedies that may be available to such other Party under this Agreement. The final
decision on the subject matter of the injunctive relief shall be subject to arbitration as foreseen in Section 11.8. 

  

	11.11	Independent Contractors; No Partnership. The Parties hereto are independent contractors. In making and performing this Agreement, the Parties are acting, and intend to be
treated, as independent entities performing a contract, and nothing contained in this Agreement is to be construed or implied or deemed to create an agency, partnership, joint venture or an employee/employer relationship between the Parties, as such
terms are given meaning under law. This Agreement is not to be deemed a partnership agreement or joint venture agreement, as such terms are given meaning under law, expressly or by implication. Employees of each Party remain employees of said Party
and will be considered at no time agents of or owing a fiduciary duty to the other Party. Neither Party hereto will have any 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 other contract, agreement or undertaking with any Third Party. 

  

	11.12	Non-Solicitation. During the Term and for two (2) years thereafter (or such shorter term as is allowed under applicable law), neither Party will, without the prior
written consent of the other Party, solicit or induce any employees of the other Party or its Affiliates who are involved in the activities contemplated by this Agreement to terminate or breach an employment, contractual or other relationship with
the other Party. Nothing in this Section 11.12 will prohibit a general solicitation made by newspaper, Internet or other media. 

  

	11.13	Audit Rights; Adjustments. 

  

	 	11.13.1	Each Party (the “Auditing Party”) will have the right to inspect the books and records of the other Party (the “Audited Party”) for purposes of
verifying compliance with financial obligations under this Agreement, including without limitation with respect to the Parties’ respective share of profits (the “Applicable Amounts”). The Audited Party will permit an
independent certified public accountant (the “Auditor”) designated by the Auditing Party and reasonably acceptable to the Audited Party, to have confidential access, at the Auditing Party’s own expense, no more than once in
each calendar year during the Term and no more than twice during the three (3) calendar years following the termination of this Agreement, during regular business hours and upon at least twenty-one (21) days’ written notice, to the
Audited Party’s records and books for the sole purpose of determining the accuracy of the Applicable Amounts reported by the Audited Party to the Auditing Party within the three (3) calendar years immediately preceding such audit by the
Audited Party. 

  

	 	11.13.2	The Auditor will be required to execute a written confidentiality agreement with the Audited Party and will disclose to the Auditing Party only the amount and accuracy of the
Applicable Amounts. The Auditor will send a copy of the report to the Audited Party at the same time it is sent to the Auditing Party. The report will also include the methodology and calculations used to determine the results.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 26 

	 	11.13.3	If such examination results in a determination that the Applicable Amounts have been overstated/understated such that a Party has received an overpayment as a consequence thereof,
such overpaid Party will remit the amount of such overpayment to the other Party within thirty (30) days following such audit. 

  

	 	11.13.4	The Auditing Party shall bear the full cost of the performance of any such audit, unless such audit discloses a variance of more than ten percent (10%) from the Applicable
Amount originally reported by the Audited Party for the applicable period under audit. In such case, the Audited Party shall bear the full cost of the performance of such audit. 

  

	11.14	Waiver. The failure of either Party to enforce any provision of this Agreement at any time will not be construed as a present or future waiver of such or any other provision
of this Agreement. The express waiver by either Party of any provision or requirement hereunder will not operate as a future waiver of such or any other provision or requirement, but any such waiver will be effective only if set forth in a written
instrument duly executed by or on behalf of the Party waiving such provision or requirement. 

  

	11.15	Amendment. This Agreement may not be amended, supplemented or otherwise modified except by an instrument in writing signed by both Parties. 

  

	11.16	Assignment. This Agreement shall be binding upon and shall inure to the benefit of the Parties hereto, their successors and permitted assigns. This Agreement may not be
assigned or transferred by either Party without the prior written consent of the other, which consent will not be unreasonably withheld or delayed, except that a Party may make such an assignment or transfer without the other Party’s consent to
Affiliates or to a successor to substantially all of the business of such Party, whether in a merger, sale of stock, sale of assets or other transaction, provided that any such assignment or transfer obligates the assignee or transferee to assume
all commitments and obligations of the assigning or transferring Party under this Agreement and the assignee or transferee agrees to be so bound, and provided further that no such assignment or transfer will relieve the assigning party of its
obligations hereunder. Any assignment or attempted assignment by either Party in violation of the terms of this Section 11.16 shall be null and void and of no legal effect. 

  

	11.17	Entire Agreement. This Agreement, including the Annexes attached hereto and the Collaboration Support Agreement between BIOLEX and OCTOSHARE dated February 11, 2005,
constitutes and contains the complete, final and exclusive undertaking and agreement of OCTOPLUS and BIOLEX hereto, and cancels and supersedes any and all prior negotiations, correspondence, understandings and agreements whether oral or written,
between the Parties respecting the subject matter herein. Notwithstanding the preceding sentence, the Feasibility Agreement shall remain in full force and effect and shall not be affected by this Section 11.17. To the extent that the terms and
conditions of this Agreement and the Feasibility Agreement conflict, the terms and conditions of this Agreement shall control. 

  

	11.18	Execution of Agreement; Counterparts. This Agreement and any amendment hereto may be executed in any number of counterparts, each of which when executed and delivered shall
be deemed to be an original and all of which counterparts taken together shall constitute but one and the same instrument. The exchange of copies of this Agreement or amendments thereto and of signature pages by facsimile transmission shall
constitute effective execution and delivery of such instrument(s) as to the Parties and may be used in lieu of the original Agreement or amendment for all purposes. Signatures of the Parties transmitted by facsimile shall be deemed to be their
original signatures for all purposes. 

 [signature page follows] 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 
 27 

 CONFIDENTIAL 
  

 [Signature page to Collaboration Agreement] 
 IN WITNESS WHEREOF, the Parties hereto have executed this Agreement by their respective officers thereunto duly authorized. 
  

					
	BIOLEX, Inc.	 		 	OCTOPLUS Technologies B.V.
			
	 /s/ Jan Turek
	 		 	 /s/ Leo de Leede

	Mr. Jan Turek	 		 	Dr. Leo de Leede
	President and Chief Executive Officer	 		 	Managing Director
			
	Date: Feb. 11, 2005	 		 	Date: Feb. 11, 2005
			
		 		 	 /s/ Joost Holthuis

		 		 	Dr. Joost Holthuis
		 		 	Executive Director
			
		 		 	Date: Feb. 11, 2005

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 1: Background Patents 
 BIOLEX BACKGROUND PATENTS 
 GENETICALLY ENGINEERED
DUCKWEED 
 INVENTORS: STOMP AND RAJBHANDARI 
 U.S. PROVISIONAL APPLICATION 
 SN 60/055,474 
 FILED 8/12/1997 
 U.S. UTILITY APPLICATION

 SN 09/132,536 
 FILED 8/11/1998

 U.S. PATENT NO. 6,040,498 
 ISSUED 3/21/2000 
 U.S. DIVISIONAL APPLICATION 
 SN 09/448,105 
 FILED 11/23/1999 
 U.S. CONTINUATION APPLICATION 
 SN
09/971,754 
 FILED 10/4/2001 
 U.S. CONTINUATION APPLICATION 
 SN 10/677,441 
 FILED 10/2/2003 
 PUBLISHED 4/15/2004 
 U.S. CONTINUATION APPLICATION 
 SN
10/273,974 
 FILED 10/18/2002 
 PUBLISHED 6/19/2003 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 1 
 BIOLEX BACKGROUND PATENTS (CONTINUED) 
 PCT APPLICATION 
 SN PCT/US98/16683 
 FILED 8/11/1998

 PUBLISHED 2/18/1999 
 EUROPEAN
APPLICATION 
 SN EP19980939350 
 JAPANESE APPLICATION 
 SN 2000-506820 
 CANADIAN APPLICATION 
 SN 2,288,895 
 AUSTRALIAN PATENT NO. 755632 
 ISSUED
4/17/2003 
 AUSTRALIAN DIVISIONAL APPLICATION 
 SN 2003/201834 
 FILED 3/19/2003 
 CHINESE APPLICATION 
 SN 98806897.4

 MEXICAN APPLICATION 
 SN
001464 
 ISRAELI APPLICATION 
 SN 132,580 
 HONG KONG APPLICATION 
 SN 01102104.8 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 1 
 BIOLEX BACKGROUND PATENTS (CONTINUED) 
 EXPRESSION OF BIOLOGICALLY ACTIVE PROTEINS IN DUCKWEED 
 INVENTORS: STOMP, DICKEY, AND GASDASKA 
 U.S. PROVISIONAL APPLICATION

 SN 60/221,705 
 FILED 7/31/2000 
 EXPRESSION OF BIOLOGICALLY ACTIVE PROTEINS IN DUCKWEED 
 INVENTORS: STOMP, DICKEY, AND GASDASKA 
 U.S. PROVISIONAL APPLICATION 
 SN 60/293,330 
 FILED 5/23/2001 
 U.S. UTILITY APPLICATION 
 SN 09/915,873

 FILED 7/26/2001 
 PUBLISHED
7/4/2002 
 U.S. PATENT NO. 6,815,184 
 ISSUED 11/9/2004 
 U.S. CONTINUATION-IN-PART APPLICATION 
 SN 10/675,011 
 FILED 9/30/2003 

PCT APPLICATION 
 SN PCT/US04/011968

 FILED 4/16/2004 
 ALPHA
INTERFERON VARIANTS 
 PCT APPLICATION 
 SN PCT/US04/11965 
 FILED 4/16/2004 
 U.S. CONTINUATION-IN-PART APPLICATION 
 SN 10/794,615 
 FILED 3/5/2004 
 U.S. DIVISIONAL
APPLICATION 
 SN 10/873,846 
 FILED 6/22/2004 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 1 
 BIOLEX BACKGROUND PATENTS (CONTINUED) 
 PCT APPLICATION 
 SN PCT/US01/23400 
 FILED 7/26/2001

 PUBLISHED 2/7/2002 
 AUSTRALIAN APPLICATION 
 SN 2001288226 
 CANADIAN APPLICATION 
 SN 2,417,415 
 EUROPEAN APPLICATION 
 SN 01967946.3

 CHINESE APPLICATION 
 SN
01815064 
 INDIAN APPLICATION 
 SN 107/KOLNP/2003 
 JAPANESE APPLICATION 
 SN 2002-516330 
 NEW ZEALAND APPLICATION 
 SN 523912 
 HONG KONG APPLICATION 

SN 03107543.4 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 OCTOPLUS BACKGROUND PATENTS 
 PolyActiveTM - Intellectual Property 
 The following table
lists OctoPlus’ patents and patent applications on its biodegradable PolyActiveTM polymer system. 
  

									
	PolyActiveTM Patents
					
	 Internal
 ref.No.
	  	 TITLE
	  	APPL. NO.	  	 PATENT
 NO.
	  	 Vereenigde
 ref. No.

	P-DD001/AU	  	Proteins in Polymeric Fibers	  	61327/00	  		  	P50632AU00
	P-DD001/CA	  	Proteins in Polymeric Fibers	  	2,321,321	  		  	P50632CA00
	P-DD001/EP	  	Proteins in Polymeric Fibers	  	00203388.4	  		  	P50632EP10
	P-DD001/JP	  	Proteins in Polymeric Fibers	  	2000-302236	  		  	P50632JP00
	P-DD001/US	  	Proteins in Polymeric Fibers	  	09/676,648	  		  	P50632US00
					
	P-DD002/AU	  	Poly(ether ester amide) Co-polymers	  	79710/00	  		  	P50633AU00
	P-DD002/CA	  	Poly(ether ester amide) Co-polymers	  	2,385,869	  		  	P50633CA00
	P-DD002/EP	  	Poly(ether ester amide) Co-polymers	  	00970310.9	  		  	P50633EP10
	P-DD002/JP	  	Poly(ether ester amide) Co-polymers	  	2001-526602	  		  	P50633JP00

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 

									
	PolyActiveTM Patents
					
	 Internal
 ref.No.
	  	 TITLE
	  	APPL. NO.	  	 PATENT
 NO.
	  	 Vereenigde
 ref. No.

	P-DD002/US	  	Poly(ether ester amide) Co-polymers	  	10/112,062	  		  	P50633US00
	P-DD003/PC	  	PolyActive Coatings on Medical Devices	  	PCT/NL/02/00212	  		  	P55721PC00
	P-DD005/CA	  	Polyetherester Copolymers as Drug Delivery Matrices	  	2,213,386	  		  	P20901CA00
	P-DD005/EP	  	Polyetherester Copolymers as Drug Delivery Matrices	  	97202533.2	  		  	P20901EP00
	P-DD005/EP/2	  	Polyetherester Copolymers as Drug Delivery Matrices	  	02077025.1	  		  	P20901EP10
	P-DD005/US	  	Polyetherester Copolymers as Drug Delivery Matrices	  	08/699,896	  	US 5,980,948	  	P20901US00
					
	P-PA001/AU	  	Devices for Preventing Tissue Adhesion	  	51554/93	  	670136	  	P60207AU00
	P-PA001/BE	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207BEEP
	P-PA001/CA	  	Devices for Preventing Tissue Adhesion	  	2118520	  	2118520	  	P60207CA00
	P-PA001/DE	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	69332500.3	  	P60207DEEP

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 

									
	PolyActiveTM Patents
	 Internal
 ref.No.
	  	 TITLE
	  	APPL. NO.	  	PATENT NO.	  	 Vereenigde
 ref. No.

	P-PA001/EP	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207EP00
	P-PA001/ES	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207ESEP
	P-PA001/FR	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207FREP
	P-PA001/DE	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	69332500.3	  	P60207DEEP
	P-PA001/GB	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207GBEP
	P-PA001/IT	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207ITEP
	P-PA001/JP	  	Devices for Preventing Tissue Adhesion	  	5-519441	  		  	P60207JP00
	P-PA001/KR	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	274481	  	P60207KREP
	P-PA001/LU	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207LUEP
	P-PA001/NL	  	Devices for Preventing Tissue Adhesion	  	93910809.8	  	0637229	  	P60207NLEP

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 

									
	PolyActiveTM Patents
					
	 Internal
 ref.No.
	  	 TITLE
	  	APPL. NO.	  	 PATENT
 NO.
	  	 Vereenigde
 ref. No.

	P-PA001/NO	  	Devices for Preventing Tissue Adhesion	  	304675	  	NO 304675B	  	P60207NO00
	P-PA001/SK	  	Devices for Preventing Tissue Adhesion	  	70382394	  	274,481	  	P60207SK00
	P-PA001/US	  	Devices for Preventing Tissue Adhesion	  	08/078,350	  	US 5,508,036	  	P60207US00
	P-PA001/US/2	  	Method for Preventing Tissue Adhesion	  	279,811	  	US 5,480,436	  	P60207US10
					
	P-PA004/AU	  	Solution Molding of PolyActive	  	64826/00	  		  	P49816AU00
	P-PA004/CA	  	Solution Molding of PolyActive	  	2,378,321	  		  	P49816CA00
	P-PA004/EP	  	Solution Molding of PolyActive	  	00952065.1	  		  	P49816EP10
	P-PA004/JP	  	Solution Molding of PolyActive	  	2001-514994	  		  	P49816JP00
	P-PA004/US	  	Solution Molding of PolyActive	  	10/047,427	  		  	P49816US00
					
	P-DD004/PD	  	PolyActive having improved biodegradability	  	02075764.7	  		  	P57561EP00
					
	P-DD006	  	Controlled release compositions based on block copolymers	  	Filed January 7,
2005 / no other
references
available as of
January 25, 2005.	  		  	P71932EP00

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 2: Primary Development Program 
 This Annex 2 has four (4) parts as follows: 
  

	 	A.	Internal Biolex Activities 

  

	 	B.	Internal OctoPlus Activities 

  

	 	C.	External Activities (to be conducted jointly) 

  

	 	D.	Budget for Part C 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 A. Internal Biolex Activities 
 1. Formulation optimization. 
 Goals: 
  

	 	1.0	increase IFN concentration in bulk API to 20 mg/ ml [note OP: preferably much higher, e.g. 50 mg/ml] to achieve higher loading concentrations 

  

	 	2.0	Timepoint: Q2 2005 and prior to animal tox or Ph. IIa product supply (see Biolex Production Plan) 

  

	 	3.0	If required, lyophylization development will be planned for scale up in 2006, prior to Phase III supply 

  

	 	•	 	 Start: ASAP 

 2. Manufacturing
of material for cynomolgus tox studies: 
  

	 	•	 	 Q2-Q4 2005 (see Biolex Production Plan) 

 3. Optimization of current process and manufacture of PII material 
  

	 	•	 	 Goal: 

  

	 	•	 	 Increase overall process yield and GMP compliance 

  

	 	•	 	 Bioprocessing optimization will begin Q1 2005 and run concurrently with recovery and purification optimization. Optimized procedures to be documented and fully
implemented in preparation for Ph. III study supply 

  

	 	•	 	 Recovery and purification optimization to take place Q1-Q2 2005 and prior to production for toxicology and Ph. IIa studies 

  

	 	•	 	 Optimization will include: 

  

	 	•	 	 UF/DF optimization (recovery and purification), 

  

	 	•	 	 individual column step optimization 

  

	 	•	 	 elimination of manufacturing hold points 

 4. Upscaling to P III scale 
  

	 	•	 	 Goal: establish a process capable of supplying enough API to support 60 gram polymer scale 

  

	 	•	 	 Evaluations of bioproduction lots with larger harvest volumes will be done at Pittsboro 

  

	 	•	 	 Increased production vessel size and/or number of vessel per batch will be evaluated and optimized by Q2/06 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 5. Biolex Production Plan 
  

																																					
	 	  	2005
	  	Q1	  	Q2	  	Q3	  	Q4	  	 Total
 2005

	 Activity
	  	Quality	  	1	  	2	  	3	  	Total	  	4	  	5	  	6	  	Total	  	7	  	8	  	9	  	Total	  	10	  	11	  	12	  	Total	  
	 Formulation Optimization1
	  	Research	  		  		  	[***]	  	[***]	  		  	[***]	  		  	[***]	  		  		  		  		  		  		  		  		  	[***]
	 Production of lyophilized material for formulation optimization2
	  	Research	  		  	[***]	  		  		  		  		  		  		  		  		  		  		  		  		  		  		  	
	 Process Optimization1
	  	Research	  		  		  		  		  		  		  	[***]	  	[***]	  		  	[***]	  		  	[***]	  		  	[***]	  		  	[***]	  	[***]
	 Reference std.
	  	Ref. Std.	  		  		  		  		  		  		  		  		  		  		  		  		  	[***]	  		  		  	[***]	  	[***]
	 Monkey Tox
	  	GLP	  		  		  		  		  		  		  	[***]	  	[***]	  		  		  		  		  		  		  		  		  	[***]
	 Phase II trial1
	  	GMP	  		  		  		  		  		  		  		  		  		  		  		  		  	[***]	  	[***]	  		  	[***]	  	[***]
	 Phase III scale-up1,3
	  	Research	  		  		  		  		  		  		  		  		  		  		  		  		  	[***]	  	[***]	  		  	[***]	  	[***]
	 Total
	  		  		  		  	[***]	  	[***]	  		  	[***]	  	[***]	  	[***]	  		  	[***]	  		  	[***]	  	[***]	  	[***]	  		  	[***]	  	[***]

 Comments: 
  

	 1
	 needs to be high concentration ([***]), which requires => 400 mg material
([***]) 

	 2
	 material for this activity may be purchased from a third party supplier 

	 3
	 For this activity,
additional API will be required in [***] – exact amounts to be determined by steering committee 

 Dates shown are delivery to
Octoplus: 
  

	GLP	lot has to be manufactured 1-2 months before the date required by OP ([***]) 

  

	GMP	lot(s) has to be manufactured 3 months (2 FOR Biolex release + 1 for OP release) before the date required by OP ([***]) 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 B. Internal OctoPlus Activities 
 In parallel to performing the phase I clinical trial with Interferon (IFNa) loaded PolyActive (PA) microspheres, both the formulation and the process will be optimized for Phase II (and III) production. The objectives
of the activities are defined as follows: 
  

	•	 	 Optimize formulation with respect to loading, release period and stability. 

  

	•	 	 Manufacturing of material for repeated injection cynomologus monkey study. 

  

	•	 	 Optimize production process for preparation of microspheres for Phase II. 

  

	•	 	 Develop up-scaled process for production for Phase III / market. 

 An overview of the studies to reach the objectives is given below. In addition an estimation of the API material requirements and a planning of the activities are included. 
 1. Formulation optimization 
 For the Phase I clinical trial a PolyActive microsphere formulation was developed with an IFNa loading of approximately 0.5% and a sustained release of two weeks. For the final product a higher loading (2-5%) of the
microspheres is preferred in order reduce the amount of polymer per injection and to reduce the injection volume (goal 0.5 ml). To increase the loading, a highly concentrated protein solution should be incorporated. Increase of the concentration
will be the first part of the formulation optimization study. Then the highly concentrated protein solution will be prepared to obtained high loaded microspheres. When the loading of the microspheres is increased one can expect a change in release
profile, which should be optimized. Furthermore, a decrease in stability of the formulation may occur at higher loading. In addition, a storage stability at room temperature is preferred over the current stability at 4oC. Below a brief description of the separate parts of this optimization study are given. The activities will be described in detail in several project plans. 
 1.1 Increase concentration protein solution 
 To increase the loading,
a highly concentrated protein solution should be incorporated. As the current protein solution contains 10-12 mg IFNa/ml, this should be increased to preferably 50 mg IFNa/ml. The increase of concentration can be obtained by either dialyses or by
freeze drying. Concentrating of the solution by dialyses will be performed by Biolex. OctoPlus Technologies will manufacture freeze dried IFNa to enable formulation optimization with dry powder as starting material. 
 Milestone: a concentrated IFNa solution (50 mg/ml) and/or a freezedried powder. 
 1.2 Increase IFNa loading of PolyActive microspheres 
 After obtaining a highly concentrated protein solution (preferably 50 mg IFNa/ml), the
solution will be used for the preparation of high loaded microspheres (2-5% IFNa). Several batches will be prepared to evaluate the effect of the encapsulation of the concentrated protein solution on the release profile, encapsulation efficiency and
integrity of the released protein. Based on the results, additives may be added or e.g. the freeze drying program may be changed. 
 Milestone: high loaded
microspheres (2-5% IFNa) showing a complete release (>80%). 
 1.3 Optimize release profile 
 Based on the results obtained with the high loaded microspheres, the release profile will be optimized regarding release rate and completeness of the release.
Optimization will be performed by varying e.g. the polymer composition, the size of the microspheres and the production process. For the latter, this part of the study will be coupled to the optimization of the production process (3.1). So far it
was experienced that the upscaling of the process resulted in an increase of the release rate. 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 Milestone: high loaded microspheres (2-5% IFNa) showing a complete release (>80%) for 2 weeks. 
 1.4 Improve stability final product 
 The current formulation, which will be used in Phase I showed stability of at least 4 months at 4 4oC.However, at higher
loading, one can expect a decrease in stability. In addition, a storage stability at room temperature is preferred for at least 2 years. To optimize the stability of the formulation, several formulations containing high loaded microspheres will be
prepared. The formulations may vary in amount and type of stabilizer added during the formation of the microspheres or prior to freeze dying of the microspheres. In addition, the freeze drying parameters may be optimized. Stability of the
formulations will be checked regarding release profile, completeness of the release, integrity and biological activity of the released protein in combination with e.g. the moisture content of the formulation. To save time, decisions regarding the
preferred formulation will be made based on initial (accelerated) stability date. 
 Milestone: stability data on formulations containing high loaded
microspheres 
 2. Manufacturing of material for cynomolgus monkey tox studies 
 Prior to the start of Phase II studies, a repeated dose cynomolgus monkey study is likely to be required both in Europe and US. It is assumed that 4 weekly injections are sufficient, although also 13 weekly injections
are reported in other dossiers. The current estimation of the set-up of the study is a low and high dose in line with tox program for Phase I: (i.e 60 ug IFN-A in microspheres (low dose) / 240 ug IFN-A in microspheres per injection (high dose)). For
the monkey trial, preferably high loaded microspheres containing the optimized IFNa should be used. The production of the microsphere will be under best clean conditions (not in cGMP facility). 
 Milestone: material available for animal trial 
 3. Optimization of
current process and manufacture of PII material 
 3.1 Optimization and validation current process 
 So far it was experienced that the upscaling of the process resulted in an increase of the release rate. The parameter responsible for this phenomenon is probably the
rate of removal of the solvent (DCM) inducing the hardening of the microspheres. Therefore, initial experiments will focus on the modulation of the solvent removal. Both unloaded and IFN loaded microspheres will be prepared by mimicking the solvent
removal profile of the small scale process in the upscaled process. In addition, it can be expected that a higher concentration of the IFNa solution will result in a different encapsulation efficiency. Therefore the final process set-up will be
validated preparing several (at least 3) IFNa loaded microspheres. Assuming a final loading above 2%, it is estimated that the current process on 6 gram scale is sufficient to produce the Phase II material. In case only a lower loading (< 2%)
appears to be feasible, it may be decided to increase the process scale to e.g. 10 grams. 
 Milestone: process suitable for preparation of Phase II material

 3.1 Production PII material 
 After optimization and
validation of the microsphere production process, the process will be transferred to the Production Department of OctoPlus. The aseptic process will be performed in clean room conditions. Depending on the final loading of the microspheres

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 and the scale of the process, approximately it is assumed that 5 batches of IFNa loaded microspheres have to be
manufactured. 
 Milestone: material available for Phase II trials 
 4. Upscaling to P III / commercial scale 
 The current process of 6 gram is not suitable for Phase III production. Therefore, a process has
to be established at approximately 60 gram polymer scale that is further scalable to 500 – 1000 gram scale for commercial production. This type of processes at this scale cannot be handled within the OctoPlus Facilities. Therefore, a contract
manufacturer has to be selected that can produce the material for the phase III trials and for commercial market. After selection, a process has to be developed in the facilities. First experiments will focuss on the preparation of unloaded
microspheres (or mloaded with a model protein). Than IFNa loaded microspheres will be manufactured (preferably on a smaller but representative scale to save material). Finally, a process validation has to be performed at the final scale preparing
IFN loaded microspheres. 
 Milestone: process suitable for preparation of Phase III material 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 OctoPlus Internal Activities Timelines 
 

 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 EXECUTION COPY 
  

 C. External Activities (to be conducted jointly) 
  

	 	1.	Pre-clinical studies in monkeys 

  

	 	2.	Other pre-clinical studies: optional, to be determined by steering committee 

  

	 	3.	Phase IIa trial 

  

	 	4.	Business development costs for preparation of commercialization 

 1.
Pre-clinical studies in monkeys 
 Preclinical safety outline PolyActive- IFNa to enable Clinical Phase II 
 Subcutaneous Maximum Tolerated Dose Study in Cynos 
  

							
	 Duration
	 	 Species
	 	 Route (frequency)
	 	 Guidelines

	14 days treatment	 	Cynomolgus monkey	 	 Subcutaneous injection
 (once weekly)
	 	(GLP standard)

  

					
	Study Design	  	:	  	 

			
	Observations	  	:	  	 Clinical Signs: Daily as required.
 Body weight: Twice
weekly.
 Food consumption: daily.

			
	Laboratory Investigations	  	

:	  	 Haematology: Pretrial, Day 7 and before termination.
 Clinical chemistry: Pretrial, Day 7 and before termination.
 Urinalysis: Pretrial and before termination.

			
	Terminal Studies	  	:	  	Macroscopic examination, organ weights and tissue retention.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 Repeat Dose Toxicology Study in Cynos 
  

							
	 Duration
	 	 Species
	 	 Route (frequency)
	 	 Guidelines

	 28 days treatment followed by
 28days of
recovery
	 	 Cynomolgus
 Monkey
	 	 Subcutaneous injection
 (once weekly)
	 	 World wide
 (GLP compliant)

  

													
	Study Design	  	:	  	Treatment :	  	Control	  	 -----PA-IFNa------

		  		  	 Dose level :
 Main study :

 Recovery :
	  	 0
 3m + 3f
 2m + 2f
	  	 Low
 3m + 3f
	  	 Medium
 3m + 3f
	  	 High
 3m + 3f
 2m + 2f

			
	Observations	  	:	  	 Clinical Signs: Daily as required.
 Body
weight: Weekly.
 Food consumption: Daily.
 Ophthalmoscopy:
Pretrial, Week 4, Week 4 recovery.
 ECG’s & BP’s: Pretrial, Day 2, Week 4, Week 4 recovery (two time points per occasion).

			
	Laboratory Investigations	  	:	  	 Haematology: Pretrial, Week 4, Week 4 recovery.
 Clinical chemistry: Pretrial, Week 4, Week 4 recovery.
 Urinalysis: Pretrial, Week 4, Week 4 recovery.
 Parameters to meet regulatory requirements.

			
	Antibody Analysis	  		  	 All animals for anti-IFNa2b antibody: Pretrial and Days 1, 14, 28 of treatment and Day 28 of recovery.
 Antibody analysis.

			
	Toxicokinetic Sampling	  	:	  	 All animals – Day 1 and in Week 4 of treatment (8 time points/occasion) and on Day 14 and Day 28 of recovery.
 Toxicokinetic analysis.

			
	Terminal Studies	  	:	  	 Macroscopic examination, organ weights and tissue retention.
 Histopathology examination – all animals.
 Tissues to meet regulatory requirements.

			
	 Additional parameters
 for
consideration:
	  		  	Measurement of water consumption, body temperatures, respiratory rates, extra haematological timepoints.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 2. Optional: Other pre-clinical studies 
 The Disposition of [14C]-Polyactive-IFNa in the Rat Following Subcutaneous Administration 
  

			
	Species:	  	Rat (Sprague Dawley)
		
	Number/Sex:	  	12 male
		
	Dose Regimen:	  	Single subcutaneous administration at a dose level to be decided.
		
	Study Design:	  	
		
		  	Phases 1: Four rats will receive a single subcutaneous administration. Urine and faeces will be collected daily to 168 h post dose. Expired air will be collected daily until less
than 0.5% of the dose is recovered in any one collection period (2 rats for only). At the end of the collection period, the rats will be humanely killed and carcass, gastrointestinal tract and dose site will be retained separately. Levels of total
radioactivity will be determined in each sample collected.
		
		  	Phases 2: Four rats will receive a single subcutaneous administration. Serial blood samples (ca 200 μl) will be collected at intervals up to 48 h (10 times). Plasma
will be separated by centrifugation and levels of total radioactivity determined.
		
		  	Phase 3: Four rats will receive a single subcutaneous administration. Two rats will be humanely killed at each of 2 times (to be decided) and a blood sample obtained. Levels of total
radioactivity will be determined in whole blood and plasma. Remaining plasma will be pooled for chromatographic analysis.
		
	Chromatographic	  	
	Analysis:	  	
		
		  	The profile of the radioactivity in pooled, key samples of urine and faeces (ie containing the bulk of the dose) and in pooled plasma will be investigated using a single chromatographic
method

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 3. Phase IIa Trial 
 Study outline Phase IIa 
 PolyActive - Interferon Alpha2b 
 TITLE OF STUDY 
 A double-blind, randomised, controlled study to assess the preliminary efficacy, pharmacokinetics, safety and
tolerability of a controlled release formulation (based on PolyActiveTM) of recombinant human interferon alpha-2b (IFNa2b) in chronic hepatitis C patients

 INVESTIGATOR 
 To be determined

 STUDY CENTRE(S) 
 Single centre; referral from several clinics; ALTERNATIVE: 
 OR Multi centre; multiple sites including subjects locally 
 PHASE OF DEVELOPMENT 
 Iia 
 OBJECTIVES 
  

	1.	To assess the pharmacodynamic effects of IFNa2b on the viral load in patients suffering from chronic hepatitis C 

  

	 2.
	 To assess the pharmacokinetics of IFNa2b released from the PolyActiveTM
 microsphere formulation 

  

	 3.
	 To assess the safety, tolerability and immunogenicity of the PolyActiveTM-IFNa2b formulation 

  

	4.	To compare the pharmacodynamics, pharmacokinetics, safety and tolerability of PolyActive-IFNa2b with a reference product 

 METHODOLOGY 
 Multiple-dose, double-blind, randomised,
controlled study in patients suffering from chronic hepatitis C. 
 After a confinement on day -1,
subjects will receive the following day one dose of PolyActiveTM-IFN a2b formulation, or PEG-Intron (PEGylated version of IFN a2b) subcutaneously; dosing
will be repeated after 2 weeks; in total 6 administrations will be performed and patients will be followed for an additional 28 days. 
 Subjects will
be studied in sub-groups, to allow for an evaluation of pharmacokinetic and safety & tolerability parameters after each group has been dosed. If necessary, modifications to the study design and/or dose may be made upon such evaluation.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 METHODOLOGY (continued) 
 Target dose in the first group X μg [TBD] IFNa2b, and for the second group 2X μg IFNa2b; dose level in first group will depend on outcome of the phase I study in healthy volunteers; dose level in second
group will also depend on initial findings in first dose group in this study. The target peak serum levels are 60 units/ml and 175 units following single dose and repeated dose respectively, and trough levels of 7-14 units/ml. 
 Patients are anticipated to be on ribavirin therapy, which will be continued during the entire study. 
 Subjects are to refrain from exercise other than the normal daily activities and will maintain a diet. In addition, subjects will refrain from smoking and alcohol consumption and limit intake of caffeinated drinks to
a maximum of three units per day. 
 An extension of the study will be proposed to the regulatory authorities and to the clinical pharmacology unit/reference
center: anticipated extension of treatment to 24 weeks in all responding subjects 
 NUMBER OF SUBJECTS 

 [60-90] chronic hepatitis C patients; [# TBD with statistician] 
 DIAGNOSIS AND MAIN CRITERIA FOR INCLUSION 
  

	 	1.	Male patients suffering from hepatitis C 

  

	 	2.	HCV diagnosis since 10 [?] years 

  

	 	3.	Age between 21[?] and 50 years 

  

	 	 4.
	 Body mass index between 20 and 28[?] kg/m2 

 TEST PRODUCT, DOSE AND
MODE OF ADMINISTRATION 
 IFNa2b formulated in
PolyActiveTM microspheres, administered subcutaneously on 6 occasions; increasing target dose per group to be administered X μg per injection, and 2X
μg per injection. 
 The source of the IFNa2b is Biolex Inc. 
 DURATION OF TREATMENT 
 Six repeated administrations; 2-week intervals

 REFERENCE THERAPY, DOSE AND MODE OF
ADMINISTRATION 
 PEGylated interferon a2b (PEG-Intron) administered subcutaneously on six repeated occasions 
 Concommitant therapy with ribavirin will be continued 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 CRITERIA FOR EVALUATION 
 Pharmacokinetic parameters 
  

	•	 	 Interferon alpha levels 

 Pharmacodynamic
parameters 
  

	•	 	 HCV-RNA titers 

 Effect parameters 

  

	•	 	 Neopterin 

  

	•	 	 2,5-OAS 

 Safety & tolerability

  

	•	 	 Local tolerability at injection site 

  

	•	 	 Immunogenicity: antibodies versus IFN-alpha and antibodies against host plant proteins 

  

	•	 	 Frequency and number of adverse events 

  

	•	 	 ECG 

  

	•	 	 Safety hematology [extensive] and biochemistry parameters 

  

	•	 	 Urinalysis 

 STATISTICAL
METHODS 
 SAMPLE SIZE JUSTIFICATION 
 The sample size will be justified by power calculation [to be performed] 
 STATISTICAL ANALYSIS 
 IFN-alpha levels will be depicted as mean ± SEM, median, minimum and maximum at
each time point. 
 Descriptive statistics will be used for description of the frequency and nature of the adverse events. The number and frequency of all
adverse events and the adverse events considered possibly or probably related to study will be listed per treatment group by body system and by coded term. In addition, the number of patients experiencing an adverse event will be listed by body
system and by coded term. 
 Biochemical and hematology parameters will be expressed as mean ± SD, median, minimum and maximum per visit. 

4. Business development costs for preparation of commercialization. 
 Upon
approval by the Steering Committee certain business development activities may be outsourced in preparation of commercialization of the Product and identification of suitable partners, including but not limited to obtaining patent opinions, market
research for the Product, and Product branding. 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 D. Budget for Part C 
  

	 	1.	Pre-clinical studies in monkeys 

  

	 	2.	Optional: other pre-clinical studies 

  

	 	3.	Phase IIa trial 

  

	 	4.	Business development costs for preparation of commercialization. 

 1. Pre-clinical studies in monkeys 
 Costs To be split as follows: 65% paid by OctoPlus and 35% paid by Bolex 
  

			
	 STUDY TITLE / DESCRIPTION
	  	 Estimated costs
 in Euro’s 

	 SC Max Tolerated Dose Study in Cynomolgus Monkey
	  	[***]
		
	 SC Repeat Dose Toxicity Study in Cynomolgus Monkeys
	  	
		
	 28 day + 28 day recovery
	  	[***]

 2. Other pre-clinical studies (optional – subject to approval by Steering Committee 
 Costs of all pre-clinical studies other than monkey studies mentioned under 1 to be split as follows: 50% paid by OctoPlus and 50% paid by Bolex 
  

			
	 STUDY TITLE / DESCRIPTION
	  	 Estimated costs
 in Euro’s 

	 Disposition Study in Rats
	  	[***]
		
	 Safety Pharmacology
	  	
		
	 Central nervous functions (Rat) – Irwin screen
	  	[***]
	 In vivo Rat respiratory function study
	  	[***]
	 In vivo cardiovascular effects in telemetered monkeys
	  	optional

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 3. Phase IIa Trial 
  

	•	 	 Costs to be split equally between Biolex and OctoPlus 

  

	•	 	 The Phase IIa Trial budget will be estimated by the Steering Committee. 

  

	•	 	 The total budget for Part C is as follows: 

 Biolex: $[***]. 
 OctoPlus: Euro [***] (= US$ [***] as of Effective Date) 
 4. Business development costs for preparation of commercialization. 
 Costs
of any such undertakings approved by the Steering Committee shall be split equally between Biolex and OctoPlus. 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 3: Manufacturing Costs 
 “OCTOPLUS Manufacturing Costs” shall mean the costs incurred by OCTOPLUS to manufacture and release Product for commercial sale which shall be determined as
follows: 
  

	 	•	 	 depreciation expenses related to investments in dedicated manufacturing facilities, excluding (manufacturing) equipment, shall be allocated proportionally (on the
basis of capacity used to manufacture Product as a percentage of total available capacity) and shall be based on linear depreciation over 30 years 

  

	 	•	 	 depreciation expenses related to investments in dedicated manufacturing equipment shall be allocated proportionally (on the basis of capacity used to manufacture
Product as a percentage of total available capacity) and shall be based on linear depreciation over 5 years 

  

	 	•	 	 direct costs (labor / material) shall be allocated on an hourly / material use basis to the extent directly related to manufacture and release of Product for
commercial sale including: 

  

	 	 •
	 	 manufacturing and release of PolyActiveTM and final product

  

	 	•	 	 equipment maintenance – calibration, certification and preventive maintenance 

  

	 	•	 	 on site storage and shipping of final product 

  

	 	•	 	 QC/QA costs – testing (in-process, product, raw material, environmental), documentation, QA reviews and product release, stability program

  

	 	•	 	 facility costs – maintenance labor and materials, utility costs (water, electricity, waste disposal), housekeeping 

  

	 	•	 	 A margin of 25% of total depreciation expenses and direct costs as defined above shall be included in the OCTOPLUS Manufacturing Costs.

  

	 	•	 	 Direct outsourcing costs shall be allocated in full without any further addition 

  

	 	•	 	 no other costs shall be included in determining OCTOPLUS Manufacturing Costs 

 “BIOLEX Manufacturing Costs” shall mean the costs incurred by BIOLEX to manufacture and release Active Ingredient to be included in Product for commercial sale and which shall be determined as follows:

  

	 	•	 	 depreciation expenses related to investments in dedicated manufacturing facilities, excluding (manufacturing) equipment, shall be allocated proportionally (on the
basis of capacity used to manufacture Active Ingredient as a percentage of total available capacity) and shall be based on linear depreciation over 30 years 

  

	 	•	 	 depreciation expenses related to investments in dedicated manufacturing equipment shall be allocated proportionally (on the basis of capacity used to manufacture
Active Ingredient as a percentage of total available capacity) and shall be based on linear depreciation over 5 years 

  

	 	•	 	 direct costs (labor / material) shall be allocated on an hourly / material use basis to the extent directly related to manufacture and release of Active Ingredient
to be included in Product for commercial sale including: 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

	 	•	 	 manufacturing and release of API 

  

	 	•	 	 maintenance of Master Plant Bank – offsite storage of duplicate as well 

  

	 	•	 	 equipment maintenance – calibration, certification and preventive maintenance 

  

	 	•	 	 on site storage and shipping of API 

  

	 	•	 	 QC/QA costs – testing (in-process, product, raw material, environmental), documentation, QA reviews and product release, stability program

  

	 	•	 	 facility costs – maintenance labor and materials, utility costs (water, electricity, waste disposal), housekeeping 

  

	 	•	 	 A margin of 25% of total depreciation expenses and direct costs as defined above shall be included in the BIOLEX Manufacturing Costs. 

 

	 	•	 	 Direct outsourcing costs shall be allocated in full without any further addition 

  

	 	•	 	 no other costs shall be included in determining BIOLEX Manufacturing Cost 

 A possible profit on manufacturing in case of supply of Product for commercial sale to an unrelated third party (“Manufacturing Profit”) shall be determined as follows: 
  

	 	•	 	 Manufacturing Profit shall be supply price to third party minus OCTOPLUS Manufacturing Costs minus BIOLEX Manufacturing Costs

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 ANNEX 4: Insurance Cover Sheets 
  

			
	ACORDTM CERTIFICATE OF LIABILITY INSURANCE	  	 DATE(MM/DD/YY)
 01/18/05        

  

							
	 PRODUCER
 Aon Risk Services, Inc. of
North Carolina
 2300 Rexwoods Drive
 Suite 200
 Raleigh NC 27607
	 		 	THIS CERTIFICATE IS ISSUED AS A MATTER OF INFORMATION ONLY AND CONFERS NO RIGHTS UPON THE CERTIFICATE HOLDER. THIS CERTIFICATE DOES NOT AMEND, EXTEND OR ALTER THE COVERAGE AFFORDED
BY THE POLICIES BELOW.
			
		 		 	COMPANIES AFFORDING COVERAGE
				
	PHONE - (866) 522-9134        FAX - (800) 724-2083	 		 	COMPANY	 	    Federal Insurance Company
		 		 	A	 
				
	 INSURED
 Biolex, Inc.
 158 Credle Street
 Pittsboro NC 27312
USA
	 		 	 COMPANY
 B
 COMPANY
 C
	 	
		 		 	 COMPANY
 D
	 	

 COVERAGES 
 THIS IS TO CERTIFY THAT THE POLICIES OF INSURANCE LISTED BELOW HAVE BEEN ISSUED TO THE INSURED NAMED ABOVE FOR THE POLICY PERIOD INDICATED. NOTWITHSTANDING ANY REQUIREMENT, TERM OR CONDITION OF ANY CONTRACT OR OTHER DOCUMENT WITH RESPECT TO
WHICH THIS CERTIFICATE MAY BE ISSUED OR MAY PERTAIN, THE INSURANCE AFFORDED BY THE POLICIES DESCRIBED HEREIN IS SUBJECT TO ALL THE TERMS, EXCLUSIONS AND CONDITIONS OF SUCH POLICIES. LIMITS SHOWN MAY HAVE BEEN REDUCED BY PAID CLAIMS. 
  

														
	 CO
 LTR
	 	 TYPE OF INSURANCE
	 	 POLICY
 NUMBER
	 	 POLICY
 EFFECTIVE
 DATE
 (MM/DD/YY)
	 	 POLICY
 EXPIRATION
 DATE
 (MM/DD/YY)
	 	 LIMITS

	A	 	GENERAL LIABILITY	 	35811307	 	04/20/04	 	04/20/05	 	GENERAL AGGREGATE	 	$	      [***]
		 	x  COMMERCIAL GENERAL LIABILITY	 	Domestic Package	 		 		 	PRODUCTS - COMP/OP AGG	 		
		 	 ̈  CLAIMS MADE  x OCCUR	 		 		 		 	PERSONAL & ADV INJURY	 	$	[***]
		 	 ̈  OWNER’S & CONTRACTOR’S PROT	 		 		 		 	EACH OCCURRENCE	 	$	[***]
		 	 ̈                                      
              	 		 		 		 	FIRE DAMAGE (Any one fire)	 	$	[***]
		 	 ̈	 		 		 		 	MED EXP (Any one person)	 	$	[***]
							
		 	AUTOMOBILE LIABILITY	 		 		 		 	  
 COMBINED SINGLE LIMIT
	 		
							
		 	 ̈  ANY AUTO	 		 		 		 	BODILY INJURY	 		
		 	 ̈  ALL OWNED AUTOS	 		 		 		 	(Per person)	 		
							
		 	 ̈  SCHEDULED AUTOS	 		 		 		 	BODILY INJURY	 		
		 	 ̈  HIRED AUTOS	 		 		 		 	(Per accident)	 		
		 	 ̈  NON-OWNED AUTOS	 		 		 		 		 		
		 	 ̈                                      
              	 		 		 		 	PROPERTY DAMAGE	 		
		 	 ̈  	 		 		 		 	 		
							
		 	GARAGE LIABILITY	 		 		 		 	AUTO ONLY - EA ACCIDENT	 		
		 	 ̈  ANY AUTO	 		 		 		 	OTHER THAN AUTO ONLY:	 		
		 	 ̈                                      
              	 		 		 		 	        EACH ACCIDENT	 		
		 	 ̈  	 		 		 		 	        AGGREGATE	 		
							
		 	EXCESS LIABILITY	 		 		 		 	EACH OCCURRENCE	 		
		 	 ̈  UMBRELLA FORM	 		 		 		 	AGGREGATE	 		
		 	 ̈  OTHER THAN UMBRELLA FORM	 		 		 		 		 		
		 	WORKER’S COMPENSATION AND EMPLOYERS’ LIABILITY	 		 		 		 	  ̈  WC STATUTORY
LIMITS
  ̈  OTHER
	 		
		 	THE PROPRIETOR/       ̈ INCL	 		 		 		 	EL EACH ACCIDENT	 		
		 	PARTNERS/EXECUTIVE	 		 		 		 	EL DISEASE-POLICY LIMIT	 		
	-	 	OFFICERS ARE:            ̈ EXCL	 		 		 		 	EL DISEASE-EA EMPLOYEE	 		

 DESCRIPTION OF OPERATIONS/LOCATIONS/VEHICLES/SPECIAL ITEMS 
  

			
	CERTIFICATE HOLDER	 	CANCELLATION
		
	  
 Biolex, Inc.
 158 Credle Street
 Pittsboro NC 27312
USA
	 	SHOULD ANY OF THE ABOVE DESCRIBED POLICIES BE CANCELLED BEFORE THE EXPIRATION DATE THEREOF. THE ISSUING COMPANY WILL ENDEAVOR TO MAIL 30 DAYS WRITTEN NOTICE TO THE CETIFICATE HOLDER NAMED TO
THE LEFT, BUT FAILURE TO MAIL SUCH NOTICE SHALL IMPOSE NO OBLIGATION OR LIABILITY OF ANY KIND UPON THE COMPANY, ITS AGENTS OR REPRESENTATIVES.
		 	  
 AUTHORIZED REPRESENTATIVE

		 	Aon Risk Services, Inc. of the Carolinas
		
	ACORD 25-S (1-95)	 	©ACORD CORPORATION 1988

 Certificate No:
570002414540                                      
                                        
                                      Holder Identifier:
Biolex 
 STATEMENT OF INSURANCE 
 This is to
certify that we, ABN AMRO Bank N.V., sworn insurance brokers in Zwolle, The Netherlands, have effected a THIRD PARTY LIABILITY INSURANCE as described below: 
  

							
	Policy number	  	:	  	7.298.009.3	  	
			
	Insured	  	:	  	 Octoplus International Holding B.V.
  
 and/or
  
 OctoShare B.V.
 OctoPlus Technologies B.V.
 Chienna B.V.

 OctoPlus Development B.V.
 OctoPlus Sciences
B.V.

				
	Limit	  	:	  	EUR. [***].-	  	 per claim for bodily injury and/or property damage and all losses resulting therefrom.
 Annual aggregate EUR. [***].-

			
	Conditions	  	:	  	In conformity with the policy conditions CA-2000 with various extensions and amendments. Product liability coverage is included.
			
	Insurance period	  	:	  	1st of June 2004 till 1st of June 2005, with tacit renewal clause.
			
	Territory	  	:	  	World-wide
			
	Insurer	  	      :      	  	Chubb Insurance Company of Europe S.A.

 In case of a dispute the policy wording will be binding. 
 Zwolle, 19th, January 2004 
 ABN AMRO Bank N.V. 
 

 
 

 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 EXECUTION COPY 
  

 [PHARMACEUTICAL INNOVATORS LETTERHEAD] 
 CONFIDENTIAL 
 Biolex, Inc. 
 158 Credle Street. 
 Pittsboro, NC 27312 
 U.S.A. 
 February 15, 2007 
 Re: Amendment to the Collaboration Agreement 
 Gentlemen: 
 As agreed both parties wish to modify the controlled release LocteronTM collaboration by including an additional clinical phase IIa study prior to the originally planned IIb trials. In order to accommodate such clinical IIa study and regulate the post
phase IIa opt-out situation certain modifications to our collaboration are necessary. 
 Reference is hereby made to the Collaboration
Agreement between Biolex, Inc. (“BIOLEX”) and OctoPlus Technologies B.V. (“OCTOPLUS”) dated February 11, 2005 (the “Agreement”). All capitalized terms used in this letter amendment (the “Amendment”) and
not defined herein are defined in the Agreement. BIOLEX and OCTOPLUS desire to supplement and amend the Agreement as follows: 
  

	1.	Primary Development Program. Section 5. 1.1 of the Agreement shall be amended to read in its entirety: 

 “Prior to starting a Commercialization Program with respect to any Product, the Parties/Party that have/has not stepped out as described in
Section 5.3 will establish and perform a development program for a Phase IIa clinical trial and a Phase IIb clinical trial (which Phase IIb clinical trial shall be conducted under an IND) for Product for the indication of Hepatitis C, including
corresponding pre-clinical tests and pharmaceutical development activities necessary to carry out such clinical program, together with any and all other activities the Steering Committee determines to conduct in support of or preparation for the
Commercialization Program, including but not limited to obtaining patent opinions and market research for the Product and undertaking Product branding activities (all of the foregoing, collectively, the “Primary Development Program”).
Initial tasks and responsibilities of BIOLEX and OCTOPLUS, as well as the anticipated budget, for the Primary Development Program are specified in Annex 2. Subject to stepping out according to Section 5.3, each Party will conduct its Primary
Development Program activities as specified in Annex 2 and as otherwise established by the Steering Committee from time to time. 
 Each Party
will use Commercially Reasonable Efforts to conduct its assigned tasks and responsibilities within the budget limits specified in Annex 2 or otherwise approved by the Steering Committee, and neither will be obligated to conduct such activities to
the extent doing so, would require incurring expenses beyond ten percent (10%) of the budgeted amount, thus amounting in total to 110% (one hundred and ten percent) of those amounts.” 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

	2.	OCTOPLUS Steps Out. Section 5.4.5 of the Agreement shall be amended to read in its entirety: 

 “Notwithstanding anything to the contrary herein including in Annex 2 or Annex 3, (i) BIOLEX shall be entitled to recover all Third Party costs
paid by BIOLEX that were not shared equally or as set forth in Annex 2 by the Parties prior to any allocation of Third Party proceeds between OCTOPLUS and BIOLEX pursuant to Section 6.5; and (ii)(a) if OCTOPLUS steps out prior to the date that
the Steering Committee determines in writing that the Phase IIa clinical trial under the Primary Development Program has been completed or prior to making all payments associated with such clinical trial that OCTOPLUS is required to make under
Section 5.2, then OCTOPLUS’s share of any profits related to the Product for purposes of any such allocation shall be reduced to twenty-five percent (25%) of such profits and BIOLEX’s share of profits shall be increased to
seventy-five percent (75%) of such profits, or (b) if OCTOPLUS steps out on or after the date that the Steering Committee determines in writing that the Phase IIa clinical trial under the Primary Development Program has been completed and
after making all payments associated with such clinical trial that OCTOPLUS is required to make under Section 5.2, but prior to the date that the Steering Committee determines in writing that the Primary Development Program has been completed
or prior to making all payments associated with the Primary Development Program that OCTOPLUS is required to make under Section 5.2, then OCTOPLUS’s share of any profits related to the Product for purposes of any such allocation shall be
reduced to thirty-five percent (35%) of such profits and BIOLEX’s share of profits shall be increased to sixty-five percent (65%) of such profits. For the avoidance of doubt, if OCTOPLUS steps out on or after the date that the
Steering Committee determines in writing that the Primary Development Program has been completed and after making all payments associated with the Primary Development Program that OCTOPLUS is required to make under Section 5.2, the profit
shares of the Parties will be as set forth in Section 6.5 and will not be adjusted pursuant to clause (ii) of the immediately preceding sentence.” 
  

	3.	BIOLEX Steps Out. Section 5.5.5 of the Agreement shall be amended to read in its entirety: 

 “Notwithstanding anything to the contrary herein including in Annex 2 or Annex 3, (i) OCTOPLUS shall be entitled to recover any direct Third
Party costs paid by OCTOPLUS that were not shared equally or as set forth in Annex 2 by the Parties prior to any allocation of Third Party proceeds between OCTOPLUS and BIOLEX pursuant to Section 6.5; and (ii) (a) if BIOLEX steps out
prior to the date that the Steering Committee determines in writing that the Phase IIa clinical trial under the Primary Development Program has been completed or prior to making all payments associated with such clinical trial that BIOLEX is
required to make under Section 5.2, then BIOLEX’s share of any profits related to the Product for purposes of any such allocation shall be reduced to twenty-five percent (25%) of such profits and OCTOPLUS’s share of profits shall
be increased to seventy-five percent (75%) of such profits, or (b) if BIOLEX steps out on or after the date that the Steering Committee determines in writing that the Phase IIa clinical trial under the Primary Development Program has been
completed and after making all payments associated with such clinical trial that BIOLEX is required to make under Section 5.2, but prior to the date that the Steering Committee determines in writing that the Primary Development Program has been
completed or prior to making all payments associated with the Primary Development Program that BIOLEX is required to make under Section 5.2, then BIOLEX’s share of any profits related to the Product for purposes of any such allocation
shall be reduced to thirty-five percent (35%) of such profits and OCTOPLUS’s share of profits shall be increased to sixty-five percent (65%) of such profits. For the avoidance of doubt, if BIOLEX steps out on or after the date that
the Steering Committee determines in writing that 

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

	 	 
the Primary Development Program has been completed and after making all payments associated with the Primary Development Program that BIOLEX is required to
make under Section 5.2, the profit shares of the Parties will be as set forth in Section 6.5 and will not be adjusted pursuant to clause (ii) of the immediately preceding sentence.” 

  

	4.	Revenue Sharing from Commercialization Program. Section 6.5.1 of the Agreement shall be amended to read in its entirety: 

 “Any license fees, up-front payments, milestone payments, royalty payments, or similar payments received with respect to Product shall be shared
equally, except as set forth in Article 5 with respect to the profit share of a Party that has stepped out with respect to such Product, and as set forth in Section 7.1.4 with respect to payments related to freedom to operate with respect to
certain Background IP. Except as otherwise specified, references in this Agreement to shares of profits of the Parties or sharing of profits by the Parties shall be deemed to refer to the allocation of amounts received with respect to Product
pursuant to this Section 6.5.1.” 
  

	5.	Budget for Phase IIb. A new Section 3.8 shall be added to the Agreement and shall read in its entirety: 

 “Budget for Phase IIb. Unless otherwise agreed by the Parties, the Steering Committee will confirm and approve in writing the expected
complete budget for the Phase IIb clinical trial under the Primary Development Program in light of the results of the completed Phase IIa clinical trial no later than thirty (30) days after determining in writing that the Phase IIa clinical
trial has been completed.” 
  

	6.	Annex 2. Annex 2, Part C, subsection 3 (Phase IIa Trial) shall be deleted entirely and replaced by a new subsection 3 (Locteron Phase IIa trial), hereto attached. Annex 2,
Part D, subsection 3 (Phase IIa Trial) shall be deleted entirely and replaced by a new subsection 3 (Locteron Phase IIa trial), hereto attached. 

 All provisions of the Agreement not expressly amended by this Amendment shall remain in full force and effect. Except as set forth in this Amendment, the Agreement is not otherwise modified in any respect, and the
Agreement is ratified and confirmed. 
 Each of Biolex and OctoPlus acknowledges that it has not, as of the date of this letter, stepped out
of further development following the completion of the Phase I Clinical Trials under the Agreement. Each of Biolex and OctoPlus agrees that it is therefore committed to participate in the Primary Development Program as described in
Section 5.3.1 of the Agreement, subject to the terms and conditions thereof. 
 The Agreement, together with any exhibits and/or
schedules attached thereto and referenced therein, all as modified by this Amendment, constitutes the entire and exclusive agreement between Biolex and OctoPlus with respect to the subject matter thereof. 
 In addition to the foregoing amendments to the Agreement, OctoPlus and OctoPlus N.V. hereby acknowledge that, effective as of September 1, 2006 (the
“Merger Date”), OctoShare B.V. merged with and into its parent company, OctoPlus N.V., as a result of which all assets and liabilities of OctoShare B.V. became assets and liabilities of OctoPlus N.V. In partial consideration for amending
the Agreement as set forth in this Amendment, OctoPlus N.V. hereby confirms and agrees, effective as of the Merger Date, that all covenants and obligations of OctoShare B.V. under the Collaboration Support Agreement between Biolex and OctoShare B.V.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 
dated February 11, 2005 are and became obligations of OctoPlus N.V. and that Octoplus N.V. is bound by all terms and conditions of the Collaboration
Support Agreement applicable to OctoShare B.V. thereunder, including with respect to the amendments to the Agreement set forth in this Amendment. OctoPlus N.V. further confirms that, except as was obtained or effected prior to the Merger Date, no
authorization, approval, consent or order of, or registration or filing with, any court or other governmental body having jurisdiction over OctoPlus N.V. is required on the part of OctoPlus N.V. for the assumption of all covenants and obligations of
OctoShare B.V. as described in this paragraph. 
 If this letter accurately reflects the agreement between OctoPlus, OctoPlus N.V. and
Biolex, please so indicate by signing this Amendment in the appropriate space provided below. 
 With kind regards, 
 OctoPlus Technologies B.V. 
  

			
	By:	 	 /s/ illegible

	Name:	 	illegible
	Title:	 	Managing Director
	
	Agreed and accepted:
	
	Biolex, Inc.
		
	By:	 	 /s/ Jan Turek

	Name:	 	Jan Turek
	Title:	 	CEO
	Date:	 	February 20, 2007
	
	Approved and agreed:
	
	OctoPlus N.V.
		
	By:	 	 /s/ illegible

	Name:	 	illegible
	Title:	 	CEO
	Date:	 	February 16, 2007

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 Annex 2, Part C, subsection 3 – Locteron Phase lla trial 
 Study design: 
 All genotype 1, naïve patients 

 
  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

			
	 Protocol synopsis
  

	Name of sponsor company:	  	OctoPlus Technologies BV, Biolex Inc
		
	Drug under study:	  	LocteronTM (PolyActiveTM -Interferon alpha 2b)
		
	Title:	  	
		
		  	An open-label, randomised study to assess the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of 4 doses of LocteronTM (PolyActiveTM – Interferon Alpha
2b) given every 2 weeks to subjects with chronic hepatitis C (treatment naïve, genotype 1) on co-medication with Ribavirin.
		
	Protocol Number:	  	
		
		  	S06-200-02-002V1
		
	Rationale:	  	Several Interferon alpha 2b (IFNa2b) products have been licensed for treatment of chronic Hepatitis C, including polyethylene glycol (PEG) modified longer acting variants of interferon alpha
(IFNa) such as PEG-Intron®. The safety and efficacy profile of weekly administered PEG-Intron®, albeit improved when compared with the short-acting product Intron® A, is still associated with significant clinically-relevant side effects
(most notably flu-like symptoms) and incomplete efficacy. Hence, a controlled-release formulation (such as LocteronTM) administered e.g. once every two
weeks might cause fewer flu-like symptoms and would overcome some of the disadvantages of currently available IFNa2b compounds, which could improve treatment for Hepatitis C virus (HCV) positive subjects. Data from a Phase I study indicate that
Biolex IFNa2b (BLX-883) administered at a clinically relevant dose (3.0 MIU) has a side-effect profile comparable to Intron® A. Pharmacokinetic analysis showed that BLX-883 was bioequivalent to Intron® A. Moreover, the neopterin serum
concentration (a biomarker of activated cell-mediated immunity) observed at 3.0 MIU was similar for Biolex IFNa2b and Intro® A, demonstrating the pharmacodynamic comparability of BLX-883 to Intron® A. A further Phase I single dose escalation
study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of LocteronTM (BLX-883, 20 μg, 80 μg and 320 μg
in PolyActiveTM controlled release microspheres) in 27 male healthy volunteers, in comparison with PEG-Intron®. These doses of LocteronTM were well tolerated. The adverse event (AE) profile of LocteronTM 320 μg was similar to PEG-Intron® or possibly more favourable. The current study is designed to assess the safety and tolerability, PK, PD and preliminary efficacy of four doses of LocteronTM, in treatment naïve subjects with chronic hepatitis C virus ([HCV], genotype 1) on co-medication with ribavirin.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

					
	Objectives:	  	Primary objective(s): To assess in subjects with chronic hepatitis C receiving a weight-based oral daily dose of ribavirin, the safety, tolerability and immunogenicity of 4
dose levels of LocteronTM.
		
		  	Secondary objective(s): To assess in subjects with chronic hepatitis C receiving a weight-based oral daily dose of’ ribavirin:
			
		  	•	  	The PK profiles (IFNa2b) at 4 dose levels of LocteronTM
			
		  	•	  	The PD profiles at 4 dose levels of LocteronTM using 2’,5’-OAS (oligoadenylate synthetase)
and neopterin as biomarkers
			
		  	•	  	The preliminary efficacy of 4 dose levels of LocteronTM assessed by serial quantitation of HCV
levels
		
	Subjects and Centres:	  	Approximately 32 subjects in three to four sites in a single country ([***]) will be randomised and equally distributed to the treatment arms sequentially, with a dose ratio of
1:1:1:1. Based on a 15% drop-out rate after randomisation, it is expected that 28 subjects (7 evaluable subjects per arm) will complete the study.
			
	Inclusion criteria:	  		  	
			
		  	1.	  	Male or female subjects 3 18 years of age with chronic hepatitis C
			
		  	2.	  	Male subjects: agreeing to use, with any female partner, highly effective birth control methods during the study and within 6 months after end of treatment, and agreeing to inform their partner
of the potential risk of birth defect in case of pregnancy during study treatment, or within 6 months after end of treatment. Effective methods of contraception include tubal ligation or having had the ovaries or uterus removed (for female partner)
or vasectomy (male subject). Other effective methods are oral contraceptive pills, injections or skin patches, an intrauterine device, condom use, or a diaphragm used with spermicide.
			
		  		  	Natural family planning/ovulation timing and spermicides alone are not considered effective
			
		  	3.	  	Female subjects of child bearing potential agreeing to use two methods of contraception at the same time (oral or parenteral contraceptive drugs and barrier method) during the study and within 6
months after end of treatment
			
		  	4.	  	A positive anti-HCV antibody test 3 6 months prior to study entry and HCV ribonucleic acid
(RNA) level > 5 x 104 IU/mL at screening
			
		  	5.	  	HCV genotype 1
			
		  	6.	  	Elevated serum alanine aminotransferase (ALT) and aspartate transaminase (AST) > upper limit of normal (ULN) as determined during the screening period
			
		  	7.	  	Negative urine pregnancy test for women of childbearing potential, documented within the 24-hour period prior to the first dose of study drug

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

					
		  	8.	  	Subjects should be treatment naive, without any prior therapy for hepatitis C, including approved treatment regimens
			
		  	9.	  	Subjects must be able to read and understand the informed consent form (ICF) and must be willing to sign the ICF.
			
	Exclusion criteria:	  		  	
			
		  	1.	  	Subjects with a body weight above 120 kg
			
		  	2.	  	Subjects with concurrent active infection with hepatitis B virus (HBV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
			
		  	3.	  	Previous use of antiviral HCV agents, including interferons, ribavirin and participation in any trials of anti-HCV therapy; previous or current use of non-antiviral therapy like hepatoprotectors
is not an exclusion criterion
			
		  	4.	  	Subjects with known hypersensitivity to IFNa or ribavirin, or with any other contra-indications to these medications
			
		  	5.	  	Subjects who have decompensated liver disease (Child-Pugh cirrhosis scale rating B or C) or a history of bleeding from oesophageal varices, ascites or hepatic encephalopathy
			
		  	6.	  	Subjects with chronic liver disease other than HCV (e.g. haemochromatosis, auto-immune hepatitis, alcoholic liver disease)
			
		  	7.	  	Subjects with hepatocellular carcinoma
			
		  	8.	  	Serum direct bilirubin 3 2 x ULN at screening
			
		  	9.	  	Neutrophil count £ 1500 cells/mm3 at screening
			
		  	10.	  	Platelet count £ 90,000/mm3 at screening
			
		  	11.	  	Haemoglobin £ 7.1 mmol/L for females and £ 7.8 mmol/L for males at screening
			
		  	12.	  	Serum creatinine level 3 1.5 x ULN at screening
			
		  	13.	  	Subjects with a history of severe psychiatric disease, including major depression
			
		  	14.	  	Subjects with a history of immunologically mediated disease (e.g. autoimmune thyroid disease, inflammatory bowel disease (IBD), idiopathic thrombocytopenic purpura, systemic lupus erythematosus,
autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis)
			
		  	15.	  	Subjects with severe degree (3 GOLD stage III) of chronic pulmonary disease (COPD) or
active, severe asthma
			
		  	16.	  	Subjects with severe cardiac disease (e.g. heart failure, recent [i.e. within 6 months prior to first dosing] myocardial infarction, unstable angina, serious arrhythmias, including prolonged OTc
[> 450 mSec])
			
		  	17.	  	Subjects with a history of seizures within the past 6 years
			
		  	18.	  	Subjects with active cancer or cancer within the last 5 years, or previous cancer with a high risk of recurrence, including metastatic breast cancer; non-melanoma skin cancer will not be an
exclusion criterion

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

					
		  	19.	  	Subjects with a history of solid organ transplantation or bone marrow transplantation
			
		  	20.	  	Subjects with clinical or laboratory evidence of uncontrolled thyroid disease, e.g. by thyroid stimulating hormone [TSH] > 4 mU/L
			
		  	21.	  	Subjects with severe retinopathy
			
		  	22.	  	Current abuse of alcohol or use of illicit drugs
			
		  	23.	  	Severe illness or any other condition which makes the subject, in the opinion of the investigator, unsuitable for the study
			
		  	24.	  	Subjects participating in another trial or having received investigational drugs within 12 weeks prior to screening
			
		  	25.	  	Subjects with a value of alpha-fetoprotein (AFP) > 100 ng/mL (> 82.6 IU/mL))
			
	Randomisation criteria:	  		  	
		
		  	After screening for eligibility, subjects must fulfil all of the inclusion criteria and none of the exclusion criteria to be randomised to one of the four treatment arms of the
study,
		
	Study design:	  	Multicentre, single country ([***]), European, open-label, randomised study with four treatment arms.
			
	Study drug, dose and mode of administration:	  		  	
		
		  	LocteronTM (PolyActiveTM-IFNa2b)
		
		  	LocteronTM will be studied at four dose levels and will be administered as a subcutaneous (s.c.) injection once every two weeks. Three of the treatment arms (160 μg, 320
μg, 480 μg) may run in parallel or with a stagger (i.e. the lower doses starting before the higher doses), and the fourth (640 μg) will begin subsequently with at least a 2-week stagger following the first three arms (last
subject’s 2-week visit) to assess initial safety of the preceding groups. Subjects will be randomised to treatment arms sequentially, with a dose ratio of 1:1:1:1. Should safety considerations at any dose not permit dose escalation, the
subjects randomised to the higher LocteronTM dose may be re-randomised by protocol amendment to a dose lower than the last dose tested, or further inclusion of subjects may be terminated.
		
		  	The study will comprise a screening period (1-4 weeks prior to first dosing) and a 12-week treatment period with (LocteronTM) treatment once every two weeks, with weekly clinic visits. One week after the end of the 12-week treatment period, subjects will return to the clinic for a follow-up visit. After
the follow-up visit, further care will be managed by the subject’s physician (up to 48 weeks of PEG-Intron®, at 1.5 μg/kg with weight-based ribavirin, will be provided free-of-charge).

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

					
	Co-medication, dose and mode of administration:	  		  	
		
		  	Ribavirin.
		
		  	The recommended dose for ribavirin (see Product Information Sheet) is dependent on the body weight of the subject as indicated below:
		
		  	Body weight < 65 kg: 2 x 200 mg capsules in the morning with food, 2 x 200 mg capsules in the evening with food, daily p.o. (800. mg daily)
		
		  	Body weight between 65 and 85 kg: 2 x 200 mg capsules in the morning with food, 3 x 200 mg capsules in the evening with food, daily p.o. (1000 mg daily)
		
		  	Body weight > 85 kg: 3 x 200 mg capsules in the morning with food, 3 x 200 mg capsules in the evening with food, daily p.o. (1200 mg daily)
			
	Criteria for evaluation of Safety:	  		  	
		
		  	The following safety assessments will be performed:
			
		  	•	  	AEs spontaneously reported and actively queried pre-dose on Day 1, on Days 2, 3 and 4 and at Weeks 2 to 14 (Follow-up) inclusive
			
		  	•	  	Physical examination, including local tolerability on Day 1 (pre-dose), on Days 2, 3 and 4, and weekly at Weeks 2, 3, 4, 5, 7, 9, 11 and 14 (Follow-up)
			
		  	•	  	Laboratory examinations at pre-dose on Day 1, on Day 3 and at Weeks 2, 3, 5, 7, 9, 11 and at follow-up (Week 14) (lab chemistry), and at Day 1 (pre-dose), and at Weeks 5 and 9 and at follow-up
(Week 14) (lab urine testing). Immunogenicity evaluations at pre-dose on Day 1 and at Weeks 5, 9 and 14 (Follow-up). Electrocardiogram (ECG) pre-dose on Day 1 and at Weeks 7 and 14 (Follow-up).
			
	Criteria for evaluation Of Efficacy:	  		  	
		
		  	This study is primarily a safety study, and only explores efficacy in terms of: Primary efficacy variable:
			
		  	•	  	 Log decrease in HCV RNA at 4 weeks compared to baseline.
  

		  	Secondary efficacy variables:
			
		  	•	  	Proportion of subjects in each arm of the study showing a 2 logs or greater drop in HCV RNA after 12 weeks of treatment (i.e. at Week 13) compared to baseline
			
		  	•	  	Proportion of subjects with HCV RNA eradication (levels below lower limit of quantification [LLQ] of 15 IU/mL; Roche Taqman) after 12 weeks of treatment (i.e. at Week 13)

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

					
		  	•	  	Log decrease of HCV RNA levels at Days 2, 3, 4 and Weeks 2 to 14 versus baseline (pre-dose on Day 1)
			
		  	•	  	Serum neopterin and 2’,5’-OAS levels taken at Day 1 (pre-dose) and Days 2, 3 and 4 and at Weeks 2, 3, 4, 5, 7, 9, 11, and 13
			
		  	•	  	Exposure of IFNa2b at pre-dose (Day 1) and at 1, 3, 6, and 12 hours after first administration (Day 1), 24 and 36 hours (Day 2), 48 hours (Day 3) and 72 hours (Day 4) after first administration,
at Weeks 2, 3, 5, 7, 9 and 11 (pre-dose trough levels at dosing visits) and at Weeks 13 and 14 (Follow-up) (exposure measured by enzyme-linked immunosorbent assay [ELISA] and bioactivity assay).
		
	Statistical methods:	  	Sample size
		
		  	 It is planned that approximately 32 subjects in total will be randomised, and with an expected drop-out rate of 15% after randomisation,
it is expected that 28 subjects will complete the study.
  

		  	Safety
		
		  	The primary objective is to assess the safety, tolerability and immunogenicity of 4 doses of LocteronTM.
		
		  	The safety analysis population will comprise all subjects who take medication. Safety analyses will be performed according to the as-treated principle.
		
		  	AEs volunteered throughout the study will be classified as per the Medical Dictionary for Regulatory Activities (MedDRA) dictionary. Those considered to be treatment-emergent will be
summarised by system organ class as the number and percentage of subjects reporting each AE by dose group. In addition, the number and percentage of subjects that volunteered adverse drug reactions by severity and where causality for the AE has been
assigned as possibly or probably related to study medication will be summarised by dose group. No formal statistical comparisons are planned.
		
		  	Flu-like symptoms are one key consideration; the incidence rates and duration of such symptoms will be compared with previously known incidence.
		
		  	 Appropriate summary statistics will be presented by dose group for other safety parameters such as laboratory data, vital signs, physical
education, ECG etc.
  

		  	Efficacy
		
		  	Preliminary efficacy of the 4 doses of LocteronTM will be assessed.
		
		  	The first endpoint for this exploratory analysis is the proportion of subjects that have at least a log drop in HCV RNA at 4 weeks compared to baseline. Response rates within each
treatment group will be estimated. The 80% and 95% confidence limits will also be summarised. Subjects who do not have a 4 week HCV RNA value will be assumed to be a non-responder.

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 

							
			
		  		  	Other efficacy endpoints will include:
				
		  		  	•	  	Proportion of subjects that have at least a 2 log drop in HCV RNA by week 12 compared to baseline
				
		  		  	•	  	Proportion of subjects showing HCV RNA eradication (levels below LLQ 15 IU/mL at week 12
				
		  		  	•	  	Log decrease of HCV RNA levels
				
		  		  	•	  	Serum neopterin levels
				
		  		  	•	  	Serum 2’,5’-OAS levels
				
		  		  	•	  	Serum IFNa2b levels
		
		  	 At each timepoint, the following descriptive statistics will be displayed for each quantitative variable: n, mean, standard deviation,
median, minimum, maximum. Qualitative variables will be presented at each time point as category counts and percentages. Summaries will be presented by dose group.
  

		  	Significance testing and estimation
		
		  	 Due to the nature of the study, no formal statistical comparisons are planned. All analyses will be descriptive.
  

		  	Sample size and justification
		
		  	 It is planned that approximately 32 subjects in total will be randomised and with an expected drop-out rate of 15% after randomisation it
is expected that 28 subjects (7 evaluable subjects per arm) will complete the study. The sample size of 32 subjects is based on clinical judgement and/or practical considerations and not on statistical considerations. However, with 8 subjects per
group, there is an 80.0% probability of detecting an AE with an underlying incidence rate of 0.18.
  

		  	Interim analysis
		
		  	No interim evaluation of the data is planned. Safety will be assessed on an ongoing basis. Before proceeding to the highest dose from the preceding doses, the following stopping
rules will apply:
				
		  		  	•	  	All subjects in the preceding LocteronTM group report symptoms of influenza-like illness of moderate or severe intensity after the 1st injection, and/or
				
		  		  	•	  	Two or more subjects in the preceding LocteronTM group report symptoms of influenza-like illness of
severe intensity after the 1st injection and for a total duration of more than 24 hours, and/or

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

					
		 	•	  	Two or more subjects in the preceding LocteronTM group report a SAE that has a potential relation with treatment, and/or
			
		 	•	  	One or more subjects in the preceding LocteronTM group report a SAE that has a probable or definite
relation with treatment.
		
	Study start date:	 	July 2006
		
	Study end date:	 	September 2007

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act. 

 CONFIDENTIAL 
  

 Annex 2, Part D, subsection 3 — Locteron Phase IIa trial 
 Budget out of pocket expenses: 
  

					
	[***]	 	[***] Euro	 	
	[***]	 	[***] Euro	 	
	[***]	 	[***] USD	 	
	[***]	 	[***] Euro	 	

  

 Portions of this Exhibit were omitted and have been filed separately with the Secretary of the Commission pursuant to
the Company’s application requesting confidential treatment under Rule 406 of the Securities Act.Supplemental Indenture dated as of August 30,2007

 Exhibit 4.1 
 This instrument was prepared by, 
 and when recorded should be 
 returned to: 
 Richard W. Astle 
 Sidley Austin LLP

 One South Dearborn Street 
 Chicago, Illinois 60603 

 

 SUPPLEMENTAL
INDENTURE 
 Dated as of August 30, 2007 
 COMMONWEALTH EDISON COMPANY 
 to

 BNY MIDWEST TRUST COMPANY 
 and 
 D.G. DONOVAN 
 Trustees Under Mortgage Dated July 1, 1923, 
 and Certain 
 Indentures Supplemental Thereto 
 Providing for Issuance of 
 FIRST MORTGAGE 6.15% BONDS, SERIES 106 
 Due September 15, 2017 
  

 THIS SUPPLEMENTAL INDENTURE, dated as of August 30,
2007, between COMMONWEALTH EDISON COMPANY, a corporation organized and existing under the laws of the State of Illinois (hereinafter called the “Company”) having an address at 440 South
LaSalle Street, Suite 3300, Chicago, Illinois 60605, party of the first part, BNY MIDWEST TRUST COMPANY, a trust company organized and existing under the laws of the State of Illinois having an address at
2 North LaSalle Street, Suite 1020, Chicago, Illinois 60602, and D.G. DONOVAN, an individual having an address at 2 North LaSalle Street, Suite 1020, Chicago, Illinois 60602, as Trustee and Co-Trustee, respectively, under the
Mortgage of the Company dated July 1, 1923, as amended and supplemented by Supplemental Indenture dated August 1, 1944 and the subsequent supplemental indentures hereinafter mentioned, parties of the second part (said Trustee being
hereinafter called the “Trustee”, the Trustee and said Co-Trustee being hereinafter together called the “Trustees”, and said Mortgage dated July 1, 1923, as amended and supplemented by said Supplemental
Indenture dated August 1, 1944 and subsequent supplemental indentures, being hereinafter called the “Mortgage”), 
 W I
T N E S S E T H: 
 WHEREAS, the Company duly executed and delivered the Mortgage to provide for the issue of, and to secure, its bonds,
issuable in series and without limit as to principal amount except as provided in the Mortgage; and 
 WHEREAS, the Company from time to time
has executed and delivered supplemental indentures to the Mortgage to provide for (i) the creation of additional series of bonds secured by the Mortgage, (ii) the amendment of certain of the terms and provisions of the Mortgage and
(iii) the confirmation of the lien of the Mortgage upon property of the Company, such supplemental indentures that are currently effective and the respective dates, parties thereto and purposes thereof, being as follows: 
  

					
	 Supplemental
 Indenture
Date
	  	Parties	  	Providing For
			
	August 1, 1944	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Edmond B. Stofft, as Trustee and Co-Trustee	  	Amendment and restatement of Mortgage dated July 1, 1923
			
	August 1, 1946	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Edmond B. Stofft, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 1, 1953	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Edmond B. Stofft, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	March 31, 1967	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Edward J. Friedrich, as Trustee and Co-Trustee	  	Confirmation of mortgage lien

  

 -2- 

					
	Supplemental Indenture Date	  	Parties	  	Providing For
			
	April 1, 1967	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Edward J. Friedrich, as Trustee and Co-Trustee	  	Amendment of Sections 3.01, 3.02, 3.05 and 3.14 of the Mortgage and issuance of First Mortgage 5-3/8% Bonds, Series Y
			
	February 28, 1969	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	May 29, 1970	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	June 1, 1971	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 1, 1972	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	May 31, 1972	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	June 15, 1973	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	May 31, 1974	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	June 13, 1975	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	May 28, 1976	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	June 3, 1977	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	May 17, 1978	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	August 31, 1978	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien

  

 -3- 

					
	Supplemental Indenture Date	  	Parties	  	Providing For
			
	June 18, 1979	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	June 20, 1980	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 16, 1981	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 30, 1982	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 15, 1983	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 13, 1984	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 15, 1985	  	Company to Continental Illinois National Bank and Trust Company of Chicago and Donald W. Alfvin, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	April 15, 1986	  	Company to Continental Illinois National Bank and Trust Company of Chicago and M.J. Kruger, as Trustee and Co-Trustee	  	Confirmation of mortgage lien
			
	May 15, 1992	  	Company to Continental Bank, National Association and M.J. Kruger, as Trustee and Co-Trustee	  	Issuance of First Mortgage 6-1/8% Bonds, Series 82 and First Mortgage 8% Bonds, Series 83
			
	April 15, 1993	  	Company to Continental Bank, National Association and M.J. Kruger, as Trustee and Co-Trustee	  	Issuance of First Mortgage 7-5/8% Bonds, Series 92
			
	June 15, 1993	  	Company to Continental Bank, National Association and M.J. Kruger, as Trustee and Co-Trustee	  	Issuance of First Mortgage 7% Bonds, Series 93 and First Mortgage 7-1/2% Bonds, Series 94
			
	January 15, 1994	  	Company to Continental Bank, National Association and M.J. Kruger, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 1994A, 1994B and 1994C
			
	March 1, 2002	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of unregistered First Mortgage 6.15% Bonds, Series 98
			
	May 20, 2002	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 2002

  

 -4- 

					
	 Supplemental
 Indenture
Date
	  	Parties	  	Providing For
			
	June 1, 2002	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of additional unregistered First Mortgage 6.15% Bonds, Series 98
			
	October 7, 2002	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of registered First Mortgage 6.15% Bonds, Series 98 in exchange for unregistered First Mortgage 6.15% Bonds, Series 98
			
	January 13, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage 3.700% Bonds, Series 99 and First Mortgage 5.875% Bonds, Series 100
			
	March 14, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage 4.70% Bonds, Series 101
			
	April 23, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 2003
			
	August 13, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage 4.74% Bonds, Series 102
			
	September 10, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 2003B
			
	November 10, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 2003C
			
	December 5, 2003	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 2003D
			
	February 15, 2005	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Pollution Control Series 2005
			
	February 1, 2006	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage Bonds, Bank Series 2006
			
	February 22, 2006	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage 5.90% Bonds, Series 103
			
	August 1, 2006	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage 5.95% Bonds, Series 104
			
	September 15, 2006	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of additional First Mortgage 5.95% Bonds, Series 104
			
	December 1, 2006	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of First Mortgage 5.40% Bonds, Series 105
			
	March 1, 2007	  	Company to BNY Midwest Trust Company and D.G. Donovan, as Trustee and Co-Trustee	  	Issuance of additional First Mortgage 5.90% Bonds, Series 103

  

 -5- 

 WHEREAS, the respective designations, maturity dates and stated principal amounts of the bonds of each
series presently outstanding under, and secured by, the Mortgage and the several supplemental indentures above referred to, are as follows: 
  

						
	 Designation
	  	 Maturity Date
	  	Principal Amount
	 First Mortgage 8% Bonds, Series 83
	  	May 15, 2008	  	$	120,000,000
			
	 First Mortgage 7-5/8% Bonds, Series 92
	  	April 15, 2013	  	 	125,000,000
			
	 First Mortgage 7-1/2% Bonds, Series 94
	  	July 1, 2013	  	 	127,000,000
			
	 First Mortgage 5.7% Bonds, Pollution Control Series 1994B
	  	January 15, 2009	  	 	15,900,000
			
	 First Mortgage 5.85% Bonds, Pollution Control Series 1994C
	  	January 15, 2014	  	 	17,000,000
			
	 First Mortgage 6.15% Bonds, Series 98
	  	March 15, 2012	  	 	450,000,000
			
	 First Mortgage Bonds, Pollution Control Series 2002
	  	April 15, 2013	  	 	100,000,000
			
	 First Mortgage 3.700% Bonds, Series 99
	  	February 1, 2008	  	 	295,000,000
			
	 First Mortgage 5.875% Bonds, Series 100
	  	February 1, 2033	  	 	253,600,000
			
	 First Mortgage 4.70% Bonds, Series 101
	  	April 15, 2015	  	 	260,000,000
			
	 First Mortgage Bonds, Pollution Control Series 2003
	  	May 15, 2017	  	 	40,000,000
			
	 First Mortgage 4.74% Bonds, Series 102
	  	August 15, 2010	  	 	212,000,000
			
	 First Mortgage Bonds, Pollution Control Series 2003B
	  	November 1, 2019	  	 	42,200,000
			
	 First Mortgage Bonds, Pollution Control Series 2003C
	  	March 1, 2020	  	 	50,000,000
			
	 First Mortgage Bonds, Pollution Control Series 2003D
	  	January 15, 2014	  	 	19,975,000
			
	 First Mortgage Bonds, Pollution Control Series 2005
	  	March 1, 2017	  	 	91,000,000
			
	 First Mortgage Bonds, Bank Series 2006
	  	February 20, 2009	  	 	1,008,000,000
			
	 First Mortgage 5.90% Bonds, Series 103
	  	March 15, 2036	  	 	625,000,000
			
	 First Mortgage 5.95% Bonds, Series 104
	  	August 15, 2016	  	 	415,000,000
			
	 First Mortgage 5.40% Bonds, Series 105
	  	December 15, 2011	  	 	345,000,000
		  		  	 	 
		  	Total	  	$	4,611,675,000
		  		  	 	 

  

 -6- 

 WHEREAS, the Mortgage provides for the issuance from time to time thereunder, in series, of bonds of the
Company for the purposes and subject to the limitations therein specified; and 
 WHEREAS, the Company desires, by this Supplemental
Indenture, to create an additional series of bonds to be issuable under the Mortgage, such bonds to be designated “First Mortgage 6.15% Bonds, Series 106 (hereinafter called the “bonds of Series 106”) and the terms and
provisions to be contained in the bonds of Series 106 or to be otherwise applicable thereto to be as set forth in this Supplemental Indenture; and 
 WHEREAS, the bonds of Series 106 and the Trustee’s certificate to be endorsed thereon shall be substantially in the form of the General Form of Registered Bond Without Coupons and the form of the General Form of Trustee’s
Certificate set forth in Section 3.05 of the Supplemental Indenture dated August 1, 1944 to the Mortgage with such appropriate insertions, omissions and variations in order to express the designation, date, maturity date, annual interest
rate, record dates for, and dates of, payment of interest, denominations, terms of redemption and redemption prices, and other terms and characteristics authorized or permitted by the Mortgage or not inconsistent therewith; and 
 WHEREAS, the Company is legally empowered and has been duly authorized by the necessary corporate action and by an order of the Illinois Commerce
Commission to make, execute and deliver this Supplemental Indenture, and to create, as an additional series of bonds of the Company, the bonds of Series 106, and all acts and things whatsoever necessary to make this Supplemental Indenture, when
executed and delivered by the Company and the Trustees, a valid, binding and legal instrument, and to make the bonds of Series 106, when authenticated by the Trustee and issued as in the Mortgage and in this Supplemental Indenture provided, the
valid, binding and legal obligations of the Company, entitled in all respects to the security of the Mortgage, as amended and supplemented, have been done and performed; 
 NOW, THEREFORE, in consideration of the premises and of the sum of one dollar duly paid by the Trustees to the Company, and for other good and valuable consideration, the receipt of which is hereby acknowledged, the
parties hereto do hereby agree as follows: 
 SECTION 1. Designation and Issuance of Bonds of Series 106. The
bonds of Series 106 shall, as hereinbefore recited, be designated as the Company’s “First Mortgage 6.15% Bonds, Series 106.” Subject to the provisions of the Mortgage, the bonds of Series 106 shall be issuable without limitation as to
the aggregate principal amount thereof. 
 SECTION 2. Form, Date, Maturity Date, Interest Rate and Interest Payment Dates of
Bonds of Series 106. (a) The definitive bonds of Series 106 shall be in engraved, lithographed, printed or typewritten form and shall be registered bonds without coupons; and such bonds and the Trustee’s certificate to be
endorsed thereon shall be substantially in the forms hereinbefore recited, respectively. The bonds of Series 106 shall be dated as provided in Section 3.01 of the Mortgage, as amended by Supplemental Indenture dated April 1, 1967.

  

 -7- 

 (b) The bonds of Series 106 shall mature on September 15, 2017. 
 (c) The bonds of Series 106 shall bear interest at the rate of 6.15% per annum until the principal thereof shall be paid. 
 (d) Interest on the bonds of Series 106 shall be payable semi-annually on the fifteenth day of March and the fifteenth day of September in each year,
commencing March 15, 2008. March 1 and September 1 in each year are hereby established as record dates for the payment of interest payable on the next succeeding interest payment dates, respectively. The interest on each bond of
Series 106 so payable on any interest payment date shall, subject to the exceptions provided in Section 3.01 of the Mortgage, as amended by said Supplemental Indenture dated April 1, 1967, be paid to the person in whose name such bond is
registered at the close of business on March 1 or September 1, as the case may be, next preceding such interest payment date. 
 SECTION 3. Execution of Bonds of Series 106. The bonds of Series 106 shall be executed on behalf of the Company by its President or one of its Vice Presidents, manually or by facsimile signature, and shall have
its corporate seal affixed thereto or a facsimile of such seal imprinted thereon, attested by its Secretary or one of its Assistant Secretaries, manually or by facsimile signature, all as may be provided by resolution of the Board of Directors of
the Company. In case any officer or officers whose signature or signatures, manual or facsimile, shall appear upon any bond of Series 106 shall cease to be such officer or officers before such bond shall have been actually authenticated and
delivered, such bond nevertheless may be issued, authenticated and delivered with the same force and effect as though the person or persons whose signature or signatures, manual or facsimile, appear thereon had not ceased to be such officer or
officers of the Company. 
 SECTION 4. Medium and Places of Payment of Principal of and Interest on Bonds of Series 106;
Transferability and Exchangeability. Both the principal of and interest on the bonds of Series 106 shall be payable in any coin or currency of the United States of America which at the time of payment is legal tender for the payment
of public and private debts, and both such principal and interest shall be payable at the office or agency of the Company in the City of Chicago, State of Illinois, or, at the option of the registered owner, at the office or agency of the Company in
the Borough of Manhattan, The City of New York, State of New York, and such bonds shall be transferable and exchangeable, in the manner provided in Sections 3.09 and 3.10 of the Mortgage, at said office or agency. No charge shall be made by the
Company to the registered owner of any bond of Series 106 for the transfer of such bond or for the exchange thereof for bonds of other authorized denominations, except, in the case of transfer, a charge sufficient to reimburse the Company for any
stamp or other tax or governmental charge required to be paid by the Company or the Trustee. 
 SECTION 5. Denominations and
Numbering of Bonds of Series 106. The bonds of Series 106 shall be issued in the denomination of $1,000 and in such multiples of $1,000 as shall from time to time hereafter be determined and authorized by the Board of Directors of the

  

 -8- 

 
Company or by any officer or officers of the Company authorized to make such determination, the authorization of the denomination of any bond of Series 106
to be conclusively evidenced by the execution thereof on behalf of the Company. Bonds of Series 106 shall be numbered R-1 and consecutively upwards. 
 SECTION 6. Temporary Bonds of Series 106. Until definitive bonds of Series 106 are ready for delivery, there may be authenticated and issued in lieu of any thereof and subject to all of the
provisions, limitations and conditions set forth in Section 3.11 of the Mortgage, temporary registered bonds without coupons of Series 106. 
 SECTION 7. Redemption of Bonds of Series 106. (a) The bonds of Series 106 shall be redeemable, at the option of the Company, as a whole or in part, at any time upon notice sent by the Company through the
mail, postage prepaid, at least thirty (30) days and not more than forty-five (45) days prior to the date fixed for redemption, to the registered holder of each bond to be redeemed in whole or in part, addressed to such holder at his
address appearing upon the registration books, at a redemption price equal to the greater of 
 (1) 100% of the principal
amount of the bonds of Series 106 to be redeemed, plus accrued interest to the redemption date, or 
 (2) as determined by the
Quotation Agent (as hereinafter defined), the sum of the present values of the remaining scheduled payments of principal and interest on the bonds of Series 106 to be redeemed (not including any portion of payments of interest accrued as of the
redemption date) discounted to the redemption date on a semi-annual basis (assuming a 360-day year consisting of twelve 30-day months) at the Adjusted Treasury Rate (as hereinafter defined) plus twenty-five (25) basis points, plus accrued
interest to the redemption date. 
 Unless the Company defaults in payment of the redemption price, on and after the redemption date, interest will cease to
accrue on the bonds of Series 106 or portions of the bonds of Series 106 called for redemption. 
 (b) For purposes of the foregoing
Section 7(a), the following terms shall have the respective meanings set forth below: 
 “Adjusted Treasury
Rate” means, with respect to any redemption date, the rate per year equal to the semi-annual equivalent yield to maturity of the Comparable Treasury Issue, assuming a price for the Comparable Treasury Issue (expressed as a percentage of its
principal amount) equal to the Comparable Treasury Price for the redemption date. 
 “Business Day” means any
day that is not a day on which banking institutions in New York City are authorized or required by law or regulation to close. 
 “Comparable Treasury Issue” means the United States Treasury security selected by the Quotation Agent as having a maturity comparable to the remaining term of the 

  

 -9- 

 
bonds of Series 106 that would be used, at the time of selection and in accordance with customary financial practice, in pricing new issues of corporate debt
securities of comparable maturity to the remaining term of the bonds of Series 106. 
 “Comparable Treasury Price” means,
with respect to any redemption date: 
 (i) the average of the Reference Treasury Dealer Quotations for that redemption date,
after excluding the highest and lowest of the Reference Treasury Dealer Quotations; or 
 (ii) if the Trustee obtains fewer
than three Reference Treasury Dealer Quotations, the average of all Reference Treasury Dealer Quotations so received. 
 “Quotation Agent” means the Reference Treasury Dealer appointed by the Company. 
 “Reference Treasury Dealer” means (1) each of Credit Suisse Securities (USA) LLC, Morgan Stanley & Co. Incorporated and one other primary U.S. Government securities dealer in New York City (“Primary
Treasury Dealer”) selected by Wachovia Capital Markets, LLC, and their respective successors, unless any of them ceases to be a Primary Treasury Dealer, in which case the Company shall substitute another Primary Treasury Dealer; and
(2) any other Primary Treasury Dealer selected by the Company. 
 “Reference Treasury Dealer Quotations”
means, with respect to each Reference Treasury Dealer and any redemption date, the average, as determined by the Trustee, of the bid and asked prices for the Comparable Treasury Issue (expressed in each case as a percentage of its principal amount)
quoted in writing to the Trustee by that Reference Treasury Dealer at 5:00 p.m., New York City time, on the third Business Day preceding that redemption date. 
 (c) In case the Company shall desire to exercise such right to redeem and pay off all or any part of such bonds of Series 106 as hereinbefore provided, it shall comply with all the terms and provisions of Article V of
the Mortgage applicable thereto, and such redemption shall be made under and subject to the terms and provisions of Article V and in the manner and with the effect therein provided, but at the time or times and upon mailing of notice, all as
hereinbefore set forth in this Section 7. No publication of notice of any redemption of any bonds of Series 106 shall be required under Section 5.03(a) of the Mortgage. 
 SECTION 8. Book-Entry Only System. It is intended that the bonds of Series 106 be registered so as to participate in the securities
depository system (the “DTC System”) with The Depository Trust Company (“DTC”), as set forth herein. The bonds of Series 106 shall be initially issued in the form of a fully registered bond or bonds in the name of
Cede & Co., or any successor thereto, as nominee for DTC. The Company and the Trustees are authorized to execute and deliver such letters to or agreements with DTC as shall be necessary to effectuate the DTC 

  

 -10- 

 
System, including the Letter of Representations from the Company and the Trustees to DTC relating to the bonds of Series 106 (the “Representation
Letter”). In the event of any conflict between the terms of the Representation Letter and the Mortgage, the terms of the Mortgage shall control. DTC may exercise the rights of a bondholder only in accordance with the terms hereof applicable
to the exercise of such rights. 
 With respect to bonds of Series 106 registered in the name of DTC or its nominee, the Company and the
Trustees shall have no responsibility or obligation to any broker-dealer, bank or other financial institution for which DTC holds such bonds from time to time as securities depository (each such broker-dealer, bank or other financial institution
being referred to herein as a “Depository Participant”) or to any person on behalf of whom such a Depository Participant holds an interest in such bonds (each such person being herein referred to as an “Indirect
Participant”). Without limiting the immediately preceding sentence, the Company and the Trustees shall have no responsibility or obligation with respect to: 
 (i) the accuracy of the records of DTC, its nominee or any Depository Participant with respect to any ownership interest in the bonds of
Series 106, 
 (ii) the delivery to any Depository Participant or any Indirect Participant or any other person, other than a
registered owner of a bond of Series 106, of any notice with respect to the bonds of Series 106, including any notice of redemption, 
 (iii) the payment to any Depository Participant or Indirect Participant or any other person, other than a registered owner of a bond of Series 106, of any amount with respect to principal of, redemption premium, if any, on, or interest on,
the bonds of Series 106, or 
 (iv) any consent given by DTC as registered owner. 
 So long as certificates for the bonds of Series 106 are not issued as hereinafter provided, the Company and the Trustees may treat DTC or any successor securities
depository as, and deem DTC or any successor securities depository to be, the absolute owner of such bonds for all purposes whatsoever, including, without limitation, (1) the payment of principal and interest on such bonds, (2) giving
notice of matters (including redemption) with respect to such bonds and (3) registering transfers with respect to such bonds. While a bond of Series 106 is in the DTC System, no person other than DTC or its nominee shall receive a certificate
with respect to such bond. 
 In the event that: 
 (a) DTC notifies the Company that it is unwilling or unable to continue as depositary or if DTC ceases to be a clearing agency registered
under applicable law and a successor depositary is not appointed by the Company within 90 days, 
  

 -11- 

 (b) the Company determines that the beneficial owners of the bonds of Series 106 should
be able to obtain certificated bonds and so notifies the Trustees in writing or 
 (c) there shall have occurred and be
continuing a completed default or any event which after notice or lapse of time or both would be a completed default with respect to the bonds of Series 106, 
 the bonds of Series 106 shall no longer be restricted to being registered in the name of DTC or its nominee. In the case of clause (a) of the preceding sentence, the Company may determine that the bonds of Series 106 shall be
registered in the name of and deposited with a successor depository operating a securities depository system, as may be acceptable to the Company and the Trustees, or such depository’s agent or designee, and if the Company does not appoint a
successor securities depository system within 90 days, then the bonds may be registered in whatever name or names registered owners of bonds transferring or exchanging such bonds shall designate, in accordance with the provisions hereof. 

Notwithstanding any other provision of the Mortgage to the contrary, so long as any bond of Series 106 is registered in the name of DTC or its
nominee, all payments with respect to principal of and interest on such bond and all notices with respect to such bond shall be made and given, respectively, in the manner provided in the Representation Letter. 
 SECTION 9. Legends. So long as the bonds of Series 106 are held by DTC, such bonds of Series 106 shall bear the following legend:

 Unless this bond is presented by an authorized representative of the Depository Trust Company, a New York corporation
(“DTC”), to the Company or its agent for registration of transfer, exchange or payment, and any bond issued is registered in the name of Cede & Co. or in such other name as is requested by an authorized representative of DTC (and
any payment is made to Cede & Co. or to such other entity as is requested by an authorized representative of DTC), any transfer, pledge or other use hereof for value or otherwise by a person is wrongful inasmuch as the registered owner
hereof, Cede & Co., has an interest herein. 
 SECTION 10. Confirmation of Lien. The Company, for the equal and
proportionate benefit and security of the holders of all bonds at any time issued under the Mortgage, hereby confirms the lien of the Mortgage upon, and hereby grants, bargains, sells, transfers, assigns, pledges, mortgages, warrants and conveys
unto the Trustees, all property of the Company and all property hereafter acquired by the Company, other than (in each case) property which, by virtue of any of the provisions of the Mortgage, is excluded from such lien, and hereby confirms the
title of the Trustees (as set forth in the Mortgage) in and to all such property. Without in any way limiting or restricting the generality of the foregoing, there is specifically included within the confirmation of lien and title hereinabove
expressed the property of the Company legally described on Exhibit A attached hereto and made a part hereof. 
  

 -12- 

 SECTION 11. Miscellaneous. The terms and conditions of this Supplemental
Indenture shall be deemed to be a part of the terms and conditions of the Mortgage for any and all purposes. The Mortgage, as supplemented by said indentures supplemental thereto dated subsequent to August 1, 1944 and referred to in the
recitals of this Supplemental Indenture, and as further supplemented by this Supplemental Indenture, is in all respects hereby ratified and confirmed. 
 This Supplemental Indenture shall bind and, subject to the provisions of Article XIV of the Mortgage, inure to the benefit of the respective successors and assigns of the parties hereto. 
 Although this Supplemental Indenture is dated as of August 30, 2007, it shall be effective only from and after the actual time of its execution and
delivery by the Company and the Trustees on the date indicated by their respective acknowledgments hereto annexed. 
 Notwithstanding
anything to the contrary contained in the Mortgage, the maximum amount of indebtedness secured by the Mortgage shall not exceed 200% of the aggregate stated principal amount of the bonds of each series presently outstanding under, and secured by,
the Mortgage, as set forth in the Recitals to this Supplemental Indenture, except to the extent such maximum amount may be adjusted by a subsequent recorded supplemental indenture (which adjustment, and the corresponding supplemental indenture,
shall not require the consent or approval of the holders of any bonds then outstanding under the Mortgage, including the holders of the bonds of Series 106). 
 This Supplemental Indenture may be simultaneously executed in any number of counterparts, and all such counterparts executed and delivered, each as an original, shall constitute but one and the same instrument.

  

 -13- 

 (intentionally left blank) 
  

 -14- 

 IN WITNESS WHEREOF, Commonwealth Edison Company has caused this Supplemental Indenture to be executed in its name by its
Senior Vice President, Chief Financial Officer and Treasurer, and attested by its Secretary, and BNY Midwest Trust Company, as Trustee under the Mortgage, has caused this Supplemental Indenture to be executed in its name by one of its Vice
Presidents, and attested by one of its Vice Presidents, and D.G. Donovan, as Co-Trustee under the Mortgage, has hereunto affixed his signature, all as of the day and year first above written. 
  

					
		  	COMMONWEALTH EDISON COMPANY
			
		  	By:	 	 /s/ Robert K. McDonald

		  		 	Robert K. McDonald
		  		 	Senior Vice President,
		  		 	Chief Financial Officer and Treasurer
			
	 ATTEST:
	  		 	
			
	 /s/ Donna Massey
	  		 	
	Donna Massey	  		 	
	Secretary	  		 	
		
		  	BNY MIDWEST TRUST COMPANY
			
		  	By:	 	 /s/ J. Bartolini

		  		 	J. Bartolini
		  		 	Vice President
			
	 ATTEST:
	  		 	
			
	 /s/ M. Callahan
	  		 	
	 M. Callahan
	  		 	
	Vice President	  		 	
		
		  	 /s/ D.G. Donovan

		  	 D.G. Donovan

  

 -15- 

			
	STATE OF ILLINOIS	 	)
		 	)
	COUNTY OF COOK	 	)

 I, MARY E. NOLAN, a Notary Public in and for said County, in the State aforesaid, DO HEREBY
CERTIFY that Robert K. McDonald, Senior Vice President, Chief Financial Officer and Treasurer of Commonwealth Edison Company, an Illinois corporation, one of the parties described in and which executed the foregoing instrument, and Donna Massey,
Secretary of said corporation, who are both personally known to me to be the same persons whose names are subscribed to the foregoing instrument as such Senior Vice President, Chief Financial Officer and Treasurer and Secretary, respectively, and
who are both personally known to me to be Senior Vice President, Chief Financial Officer and Treasurer and Secretary, respectively, of said corporation, appeared before me this day in person and severally acknowledged that they signed, executed and
delivered said instrument as their free and voluntary act as such Senior Vice President, Chief Financial Officer and Treasurer and Secretary, respectively, of said corporation, and as the free and voluntary act of said corporation, for the uses and
purposes therein set forth. 
 GIVEN under my hand and notarial seal this 30th day of August, A.D. 2007. 
  

	
	 /s/ Mary E. Nolan

	Mary E. Nolan
	Notary Public

 (NOTARIAL SEAL) 
 My Commission expires April 23, 2009. 
  

 -16- 

			
	STATE OF ILLINOIS	 	)
		 	)
	COUNTY OF COOK	 	)

 I, T. MOSTERD, a Notary Public in and for said County, in the State aforesaid, DO HEREBY CERTIFY
that J. BARTOLINI, Vice President of BNY Midwest Trust Company, an Illinois trust company, one of the parties described in and which executed the foregoing instrument, and M. CALLAHAN, Vice President of said trust company, who are both personally
known to me to be the same persons whose names are subscribed to the foregoing instrument as such Vice Presidents, and who are both personally known to me to be Vice Presidents of said trust company, appeared before me this day in person and
severally acknowledged that they signed, executed and delivered said instrument as their free and voluntary act as such Vice Presidents of said trust company, and as the free and voluntary act of said trust company, for the uses and purposes therein
set forth. 
 GIVEN under my hand and notarial seal this 30th day of August, A.D. 2007. 
  

	
	 /s/ T. Mosterd

	 T. Mosterd

	Notary Public

 {SEAL} 
 My
Commission expires January 22, 2009. 
  

 -17- 

			
	STATE OF ILLINOIS	 	)
		 	)
	COUNTY OF COOK	 	)

 I, T. MOSTERD, a Notary Public in and for said County, in the State aforesaid, DO HEREBY CERTIFY
that D.G. DONOVAN, one of the parties described in and which executed the foregoing instrument, who is personally known to me to be the same person whose name is subscribed to the foregoing instrument, appeared before me this day in person and
acknowledged that he signed, executed and delivered said instrument as his free and voluntary act for the uses and purposes therein set forth. 
 GIVEN under my hand and notarial seal this 30th day of August, A.D. 2007. 
  

	
	 /s/ T. Mosterd

	T. Mosterd
	Notary Public

 {SEAL} 
 My
Commission expires January 22, 2009. 
  

 -18- 

 EXHIBIT A 
 LEGAL DESCRIPTIONS 
 See attached.

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