Document:

Amendment No. 3 to License Agreement

 EXHIBIT 10.3 
 Portions of this Exhibit were omitted and filed separately with the Secretary of the Commission pursuant to an application for confidential treatment filed with the Commission pursuant to Rule 24b-2 under the Securities Exchange Act of
1934. Such omissions are designated as ***. 
 AMENDMENT NO.3 TO 
 LICENSE AGREEMENT 
 DATED AS OF APRIL 13, 2002 
 BY AND BETWEEN 
 UNIGENE LABORATORIES,
INC. 
 AND 
 SMITHKLINE BEECHAM CORPORATION 
 This Amendment No. 3 (“Amendment No. 3”) dated as of 23 Sept., 2004
(“Amendment Date”), to the License Agreement, entered into as of the 13th of April, 2002, and amended on January 16, 2003 and October 14, 2003 (referred to hereinafter as the “Agreement”), by and between Unigene
Laboratories, Inc. (“Unigene”), a Delaware corporation, and SmithKline Beecham Corporation, a GlaxoSmithKline company (“GSK”), a Pennsylvania corporation. 
 RECITALS: 
 WHEREAS, GSK and Unigene entered into the Agreement to provide for the
license grant by Unigene to GSK of certain Licensed Technology (as defined in the Agreement) to discover, develop, make, have made, market, sell and import certain Licensed Products (as defined in the Agreement) throughout the world under the
Unigene Patent Rights (as defined in the Agreement) and Unigene Know-How (as defined in the Agreement); and 
 WHEREAS, GSK and Unigene have
also entered into a Phase I Clinical Manufacture and Supply Agreement dated November 20, 2002 (the “Phase I Agreement”); and 
 WHEREAS, pursuant to Section 11.10 of the Agreement, the Parties to the Agreement may, by written instruments specifically referring to and executed in the same manner as the Agreement, amend the Agreement; and 
 WHEREAS, the Parties hereto desire to amend the Agreement as provided herein, and any capitalized terms used herein shall have the meaning set forth in
the Agreement; 
 NOW THEREFORE, for and in consideration of the premises and the mutual promises and benefits contained herein, GSK and
Unigene hereby agree as follows: 
 1. Exhibit C to the Phase I Agreement (Cost of Goods) is hereby amended to add the 2004 and 2005 Cost of
Goods set forth in Appendix A to this Amendment No. 3. 

 2. Exhibit A to the Phase I Agreement (Current Manufacturing Process) is hereby amended by replacing the
existing Process Flow Diagram-PTH with the Process Flow Diagram-PTH set forth in Appendix B to this Amendment No. 3. 
 3. Appendix B to
the Agreement (the WorkPlan) is hereby amended to add the activities regarding API set forth in Appendix C to this Amendment No. 3 at the FTE costs set forth in Appendix C to this Amendment No. 3. 
 4. Article 1 of the Phase I Agreement is hereby amended to add the following new section: 
 1.25. Commercially Reasonable Efforts means, with respect to a Party, the efforts and resources which would be used (including without limitation
the promptness in which such efforts and resources would be applied) by that Party consistent with its normal business practices, which in no event shall be less than the level of efforts and resources standard in the pharmaceutical industry for a
company similar in size and scope to such Party, with respect to a product or potential product at a similar stage in its development or product life taking into account efficacy, safety, commercial value, the competitiveness of alternative products
of third parties that are in the marketplace or under development, and the patent and other proprietary position of such product. 
 5.
Section 2.3 of the Phase I Agreement is hereby amended by replacing the current language with the following language in lieu thereof: 
 Unigene shall supply GSK at least four (4) batches of API (two (2) batches shall be cGMP grade and two (2) shall be process development batches). Unigene shall use its Commercially Reasonable Efforts to achieve a fermentation
batch yield of ***. The Parties agree and acknowledge that one Changeover shall be required before supply of the first batch. Any batches in excess of four (4) shall be supplied pursuant to the terms of this Agreement, including but not limited
to, Article 4.6(b). 
 6. Article 2 of the Phase I Agreement is hereby amended to add the following new section: 
 2.9. GSK Equipment. In order to support the manufacture of GSK material requirements, GSK will purchase and Unigene will install *** Columns,
including spare parts therefore (the “Columns”), in the facility. The Parties agree that the Columns are the property of GSK and will be used solely for the purpose of manufacturing GSK material requirements. Following receipt of written
notification from GSK that Unigene will no longer be producing API for GSK for any purpose, GSK will notify Unigene of whether GSK intends to: a) keep the Columns and have them removed from the Unigene facility(ies) or, b) offer the Columns for sale
to Unigene. The parties will negotiate in good faith a price for the purchase of the Columns by Unigene, said price not to exceed the depreciated value of the Columns (straight-line depreciation over ten (10) years) minus  

  

 - 2 - 

 
Unigene’s actual FTE costs for their assembly and installation/operation qualification. In the event GSK elects to keep the Columns and have them
removed from the Unigene facility or, if the parties are unable to agree on a good faith purchase price, GSK will: a) reimburse Unigene for its actual FTE costs incurred for assembly and installation/operation qualification and, (b) reimburse
Unigene for its actual FTE costs of disassembling and unpacking the Columns prior to their return and, c) pay for any associated shipping costs incurred to ship the Columns via a GSK-approved carrier. 
 7. For the avoidance of doubt, the Parties agree and acknowledge that GSK has ordered the Columns identified in Section 6 of this Amendment and the
Columns will be shipped directly to Unigene for installation. 
 8. Section 11.1 of the Phase I Agreement is hereby is amended to
replace the words “twenty-four (24) months” with the words “thirty (30) months.” 
 9. This Amendment
No. 3 may be executed in two (2) or more counterparts, each of which shall be deemed an original but all of which together shall constitute one and the same instrument. 
 IN WITNESS WHEREOF, the Parties hereto have caused this Amendment to be duly executed by their authorized representatives as of the Amendment Date.

  

									
	UNIGENE LABORATORIES, INC.	 		 	 SMITHKLINE BEECHAM CORPORATION,
 a GlaxoSmithKline Company

					
	By:	 	 /s/ Ronald S. Levy
	 		 	By:	 	 /s/ John Knighton

	Name:	 	Ronald S. Levy	 		 	Name:	 	John Knighton
	Title:	 	Executive Vice President	 		 	Title:	 	Director, GSK

  

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 Appendix A 
 COST OF GOODS 
 The Cost of Goods* for API manufactured pursuant to the Agreement for the 2004 and 2005 calendar years is: 
 *** 
 *** 
  

	 *
	 Cost of Goods is subject to revisions as set forth in Article 2 of the Agreement. 

  

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 Appendix B 
 CURRENT MANUFACTURING PROCESS – PROCESS FLOW DIAGRAM 
 PROCESS FLOW DIAGRAM - PTH 

  

							
	 Process Steps
	  	Step
#	  	 Molecular
 Form of
 Product
	  	 Batch Records

	 Fermentation
	  	1	  		  	 *** (Shake Flask Inoculum),
 ***
(Fermentation to
         Harvesting)

	 Harvest
	  	2	  		  
	 ***
	  	3	  	rPTH-***	  	*** (Capture)
	 ***
	  	4	  		  	 ***
 (Purified PTH)

	 ***
	  	5	  		  
	 ***
	  	6	  		  
	 ***
	  	7	  	rPTH	  
	 ***
	  	8	  		  
	 ***
	  	9	  		  
	 ***
	  	10	  		  	*** (Parathyroid Hormone)
	 Bulk Parathyroid Hormone
	  		  		  	

 Appendix C 
 WORKPLAN OF UNIGENE ACTIVITIES AND FTE REQUIREMENTS 
  

												
	 	  	ESTIMATED
PERIOD	  	DURATION	 	 	UNIGENE
STAFF	 	 	MAXIMUM
COST ($)	 
	 DEVELOPMENT ACTIVITY PRIOR TO PHASE II
	  		  			 			 		
	 MANUFACTURING CAMPAIGN
	  		  			 			 		
	 Replacement of *** with *** and Optimization of *** reaction
	  	May 04 –July 04	  	7 weeks	 	 	*	**	 	*	**
					
	 Development of *** to replace *** in process steps *** and ***
	  	July 04 – Sep 04	  	9 weeks	 	 	*	**	 	*	**
		  		  	 	 	 			 	 	 
	 SUB TOTAL 
	  		  	16 weeks	 	 			 	*	**
	 TECHNOLOGY TRANSFER[1]
	  		  			 			 		
					
	 Unigene to work with GSK on validation and technology transfer prior to phase III clinical studies.
	  	TBC	  	*	**	 	*	**	 	*	**
					
	 Unigene to work with GSK on NDA preparation, validation and technology transfer at or beyond phase III clinical studies.
	  	TBC	  	*	**	 	*	**	 	*	**

  

	[1]	Timing of technology transfer dependent on manufacturing strategy to be determined. The two options are mutually exclusive and NOT additive. 

  

 - 6 -Amendment No. 4 to License Agreement

 EXHIBIT 10.4 
 Portions of this Exhibit were omitted and filed separately with the Secretary of the Commission pursuant to an application for confidential treatment filed with the Commission pursuant to Rule 24b-2 under the Securities Exchange Act of
1934. Such omissions are designated as ***. 
 AMENDMENT NO. 4 TO 
 LICENSE AGREEMENT 
 DATED AS OF APRIL 13, 2002 
 BY AND BETWEEN 
 UNIGENE LABORATORIES,
INC. 
 AND 
 SMITHKLINE BEECHAM CORPORATION 
 This Amendment No. 4 (“Amendment No. 4”) dated as of May 27, 2004
(“Amendment Date”), to the License Agreement, entered into as of the 13th of April, 2002 and amended on January 14, 2003 and October 14, 2003 (referred to hereinafter as the “Agreement”), by and between Unigene
Laboratories, Inc. (“Unigene”), a Delaware corporation, and SmithKline Beecham Corporation, a GlaxoSmithKline company (“GSK”), a Pennsylvania corporation. 
 WHEREAS, GSK and Unigene entered into the Agreement to provide for the license grant by Unigene to GSK of certain Licensed Technology (as defined in the
Agreement) to discover, develop, make, have made, market, sell and import certain Licensed Products (as defined in the Agreement) throughout the world under the Unigene Patent Rights (as defined in the Agreement) and Unigene Know-How (as defined in
the Agreement); and 
 WHEREAS, GSK and Unigene have also entered into a Phase I Clinical Manufacture and Supply Agreement dated
November 20, 2002 (the “Phase I Agreement”); and 
 WHEREAS, pursuant to Section 11.10 of the Agreement, the Parties to
the Agreement may, by written instruments specifically referring to and executed in the same manner as the Agreement, amend the Agreement; and 
 WHEREAS, the Parties hereto desire to amend the Agreement as provided herein, and any capitalized terms used herein shall have the meaning set forth in the Agreement; 
 NOW THEREFORE, for and in consideration of the premises and the mutual promises and benefits contained herein, GSK and Unigene hereby agree as follows:

 1. Appendix B to the Agreement (the Work Plan) is hereby amended to add the activities regarding PTH*** set forth in Appendix A to this Amendment
No. 4 at the FTE cost set forth in Appendix A to this Amendment No. 4. 

 2. Appendix C to the Agreement (Unigene Know-How and Technology Transfer) is hereby amended to add the technology and
know-how regarding PTH*** set forth in Appendix B to this Amendment No. 4. 
 3. Section 4.5 of the Agreement shall be amended and restated in its
entirety to read: 
 Unigene Data Transfer. Immediately after the Effective Date (or with respect to PTH *** Unigene Know-How,
immediately after the Amendment Date of Amendment No. 4 to this Agreement, as applicable), Unigene shall use its reasonable best efforts to promptly transfer, or cause to be transferred to GSK, a copy of Unigene Know-How relating to PTH and
the Licensed Product, including manufacture of API, to enable GSK to carry out its responsibilities under this Agreement. Such data shall include, at a minimum, the information set forth in Appendix C to this Agreement, attached hereto and
incorporated herein. 
 4. Appendix A to Amendment No. 2 to the Agreement, dated October 14, 2003, is hereby amended to include: 
  

			
	 Type
	  	 Designation (Designator)

	 *** Cell Bank
	  	*** (Unigene)
		
	 *** Cell Bank
	  	*** (Unigene)
		
	 ***
	  	*** (Unigene)

 5. Except as specifically provided herein, all other terms and conditions of the Agreement shall remain in full
force and effect, and this Amendment No. 4 to the Agreement shall not be construed to amend or waive any provisions of the Agreement except as specifically set forth above. 
 6. This Amendment No. 4 to the Agreement, and the rights and obligations of the Parties hereunder, shall be construed in accordance with, and governed by the laws of the Commonwealth of Pennsylvania (without
regard to its conflict of laws principles). 
 7. This Amendment No. 4 may be executed in two (2) or more counterparts, each of which shall be
deemed an original but all of which together shall constitute one and the same instrument. 
 8. This Amendment No. 4 shall inure to the benefit of and
be binding upon the GSK and Unigene and their respective successors, heirs and assigns. 

 IN WITNESS WHEREOF, the Parties hereto have caused this Amendment No. 4 to be duly executed by their authorized
representatives as of the Amendment Date. 
  

									
	UNIGENE LABORATORIES, INC.	 		 	 SMITHKLINE BEECHAM CORPORATION,
 a GlaxoSmithKline Company

					
	By:	 	 /s/ Ronald S. Levy
	 		 	By:	 	 /s/ Donald F. Parman

	Name:	 	Ronald S. Levy	 		 	Name:	 	Donald F. Parman
	Title:	 	Executive Vice President	 		 	Title:	 	Vice President & Secretary

 Appendix A 
 Summary of Unigene R&D FTE/Activities for PTH*** 
  

										
	 Activity Description
	  	Estimated
Period	 	 	Duration*	 	 	Unigene
FTE	 
	 FERMENTATION and PURIFICATION:
 Unigene to prepare
Seed Bank of *** PTH*** and perform preliminary characterization tests to test for suitability of this cell bank. The following tests will be performed: Viable cell count, Kanamycin resistance, Verification of genotype, DNA sequencing of PTH insert.
Vials of the Seed Bank will be transferred to GSK for preparation and characterization of Master and Working Cell Banks
	  	*	**	 	*	**	 	*	**
				
	 FERMENTATION and PURIFICATION:
 Unigene to
optimize fermentation of *** at the 1 liter scale to develop consistent process and optimize productivity
	  	*	**	 	*	**	 	*	**
				
	 FERMENTATION and PURIFICATION:
 Unigene to
optimize and scale up purification and amidation steps for PTH***
	  	*	**	 	*	**	 	*	**
				
	 FERMENTATION and PURIFICATION:
 Unigene to carry
out 3 fermentations at the 30 liter scale for *** and purify and amidate material from these fermentations. Unigene will provide 20 grams of non-GMP PTH *** from these purifications
	  	*	**	 	*	**	 	*	**
				
	 PTH *** IMMUNOASSAY DEVELOPMENT:
 Optimize *** for
the detection of PTH***. The *** will be the same *** antibody currently used for PTH***. The *** will be a *** that has already been prepared by Unigene that has a high titer binding for PTH***. If successful, an additional *** will be raised under
contract at *** for an approximate cost of ***
	  	*	**	 	*	**	 	*	**
				
	 PTH *** IMMUNOASSAY DEVELOPMENT:
 Epitope mapping
studies for *** PTH *** antibodies. Peptides for epitope mapping will be obtained by custom syntheses from external sources for an approximate cost of ***
	  	*	**	 	*	**	 	*	**

 FTE Cost *** 
 Total
cost for Fermentation and Purification activities (including cost of 20g non-GMP material: *** 

 Total cost of Immunoassay Development activities (to include *** purchase of peptides for *** mapping and *** for cost of
immunization at *** 

 Appendix B 
 Unigene Know-How and Technology Transfer with Respect to PTH*** 
  

	1.	All experimental details, data and documentation for pharmacology studies in any animal species with oral, subcutaneous, and IV ***PTH*** alone or compared to other peptide(s)
performed by Unigene or third party laboratories. 

  

	2.	Host cell, plasmids, documentation and experimental details for the preparation of ***PTH***, transformation and growth of cell strains expressing ***PTH***.

  

	3.	The current optimal cell strain for producing ***PTH*** and any other ***PTH*** strains deemed to be of interest to GSK. 

  

	4.	The current optimal cell line for producing the amidating enzyme and any other cell lines expressing the amidating enzyme deemed to be of interest to GSK 

 

	5.	All reagents, documentation and experimental details for expression, isolation and purification of ***PTH***. 

  

	6.	All analytical experimental details, reagents, data and documentation for characterization of ***PTH***. 

  

	7.	All reagents, documentation and experimental details for the preparation and purification of polyclonal antibodies against ***PTH***. 

  

	8.	All analytical experimental details, data and documentation for characterization of the polyclonal ***PTH*** antibodies. 

  

	9.	All experimental details, reagents, data and reports on ***PTH*** immunoassay development activity. 

  

	10.	All reagents, documentation and experimental details for running the current immunoassay against ***PTH***. 

  

	11.	All experimental details, data and documentation for pharmacokinetic studies in any animal species with oral, subcutaneousand IV ***PTH*** performed by Unigene or third party
laboratories.

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