Document:

EX-10.15

 Exhibit 10.15 
 CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT MARKED WITH [***] HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24B-2 OF THE
SECURITIES EXCHANGE ACT, AS AMENDED. 
 SUPPLY AGREEMENT 

THIS SUPPLY AGREEMENT (“THE SUPPLY
AGREEMENT”) is made effective as of the 9th day of June, 1999 (the “Effective Date”) by and between IDEC PHARMACEUTICALS CORPORATION, a Delaware corporation, having its principal place of business at 11011 Torreyana Road, San Diego,
California 92121(“IDEC”) and SCHERING AKTIENGESELLSCHAFT, a German corporation, having its principal place of business at Müllerstrasse 178, D-13342 Berlin, Germany (“SCHERING”). IDEC and SCHERING are sometimes referred to
herein individually as a “Party” and collectively as the “Parties”, and references to “IDEC” shall include its Affiliates. 
 RECITALS 
  

	1.1	WHEREAS, IDEC and SCHERING have entered into a Collaboration Agreement of even date, under which IDEC has granted to SCHERING an exclusive license to develop and
commercialize the Licensed Product(s) (as therein defined) in all countries of the world outside the United States, on the terms and subject to the conditions therein defined; 

 

	1.2	WHEREAS, SCHERING desires to secure its exclusive supply of IDEC 2B8 in Kit form (as hereinafter defined) from IDEC, and IDEC has agreed to supply SCHERING with its
requirements of IDEC 2B8 in Kit form on the terms and subject to the conditions hereinafter described; 

  

	1.3	WHEREAS, IDEC intends to manufacture and supply all of SCHERING’s requirements of the 2B8 (as hereinafter defined) from an IDEC facility; 

 

	1.4	WHEREAS, IDEC intends to enter into a supply agreement with Catalytica, Inc. for the supply (inter alia) of all of SCHERING’s requirements of the Antibody
Conjugate and Non-Antibody Components (as hereinafter defined); and 

  

	1.5	WHEREAS, IDEC has entered into a supply agreement with Nordion, Inc. whereby Nordion agreed to supply yttrium to IDEC for use in the radiolabeling of IDEC 2B8.

  

	1.6	WHEREAS, SCHERING intends to establish an independent contract with Nordion or another Third Party for supply of yttrium. 

 

	1.7	NOW, THEREFORE, THE PARTIES HERETO AGREE AS FOLLOWS: 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	1

 ARTICLE II 
 DEFINITIONS 
  

	2.1	“2B8” means the unlabeled monoclonal antibody to CD20 cells more particularly described on Exhibit B to the Collaboration Agreement and
Exhibit A of this Supply Agreement. 

  

	2.2	“Affiliate” means an entity which, directly or indirectly, through one or more intermediaries, controls, is controlled by, or is under common
control with, IDEC or SCHERING, as the case may be. As used in this definition, “control” means the direct or indirect ownership of fifty percent (50%) or more of the stock having the right to vote for directors thereof, or the
possession of the power to direct or cause the direction of the management and policies of an entity, whether through the ownership of the outstanding voting securities or by contract or otherwise. 

 

	2.3	“Allocable Overhead” means costs incurred by a Party or for its account which are attributable to a Party’s supervisory services, occupancy costs,
and its payroll, information systems, human relations and purchasing functions and which are allocated to company departments based on space occupied or headcount or other activity-based method, excluding compensation related to a Party’s stock
option program or any program that replaces such program. Allocable Overhead shall not include any costs attributable to general corporate activities including, by way of example, executive management, investor relations, business development, legal
affairs and finance. 

  

	2.4	“Antibody Conjugate” shall mean 2B8 conjugated with MxDTPA 

 

	2.5	“Antibody Manufacturing Cost” shall mean IDEC’s direct costs and charges, including Allocable Overhead, related to the manufacture, packaging and
shipment of 2B8, and shall exclude costs and charges related to or occasioned by unused manufacturing capacity, the manufacture of other products at IDEC’s facilities, amortization of property, plant or equipment not specifically related to
manufacturing 2B8, and any employee costs associated with equity incentive plans. Exhibit D to the Collaboration Agreement sets out a breakdown of IDEC’s current Antibody Manufacturing Cost. 

 

	2.6	“Business Day” shall mean a day on which banking institutions are open for business in California, U.S.A. and Berlin, Germany.

  

	2.7	“Catalytica” shall mean Catalytica Pharmaceuticals, Inc., having its principal place of business at intersection US13, NC11 and US 264, Greenville,
North Carolina 27834. 

  

	2.8	“CGMPs” shall mean both the principles detailed in the United States’ Current Good Manufacturing Practices (21 CFR 200, 211 and 600) and
“The Rules Governing Medicinal Products in the European Community – Volume IV Good Manufacturing Practice for Medicinal Products”. CGMPs will also include compliance with any applicable additional Regulatory Approval requirements.

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	2

	2.9	“Clinical Requirements” shall mean the quantities of Kits which are needed by SCHERING and its sublicensees (if any) for the conduct of preclinical and
clinical studies of Licensed Product throughout the Licensed Territory. 

  

	2.10	“Collaboration Agreement” shall mean the Collaboration and License Agreement of even date herewith between IDEC and SCHERING. 

 

	2.11	“Commercially Reasonable and Diligent” means those efforts consistent with the exercise of prudent scientific and business judgment, as applied to
other pharmaceutical products of similar potential and market size by the Party in question. 

  

	2.12	“Commercial Requirements” shall mean the quantities of Kits which are needed by SCHERING and its sublicensees (if any) for production, promotion and
sale of the Licensed Product throughout the world, excluding the United States. 

  

	2.13	“Cost of Goods Sold” shall mean the total of: [***]. 

  

	2.14	“Effective Date” shall mean June 9, 1999. 

  

	2.15	“Expiration Date” shall mean the date established by the EMEA as the case may be as the expiration date for each Kit Component.

  

	2.16	“IDEC” shall mean IDEC Pharmaceuticals Corporation, a Delaware corporation, and its Affiliates. 

 

	2.17	“Initial Phase” shall mean the period of two (2) years following the filing of a Drug Approval Application in the Licensed Territory in accordance
with Section 5.1 of the Collaboration Agreement. 

  

	2.18	“Inter-Company Quality Agreement” shall mean the Inter-Company Quality Agreement between SCHERING and IDEC of even date attached hereto to this Supply
Agreement as Exhibit B. 

  

	2.19	“Kit Expiration Date” shall mean the earliest Expiration Date of any of the Kit Components. 

 

	2.20	“Kit(s)” shall mean a set of four unlabeled vials that include (1) Antibody Conjugate, (2) sodium acetate buffer; (3) formulation
buffer; and (4) an empty 10 mL reaction vial. The Kit does not include the radioisotope that will be supplied independently by SCHERING or SCHERING’s designee. The term “Kit Component” shall mean any one of the four
individual unlabeled vials that define Kit. 

  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	3

	2.21	“Licensed Product” shall mean either Antibody Conjugate alone or Antibody Conjugate plus Non-Antibody Components or Y2B8 or, where the Imaging step is
required in any country or territory of the Licensed Territory, Antibody Conjugate or Antibody Conjugate plus Non-Antibody Components or Y2B8 and In2B8 in either case as (a) developed by IDEC or (b) the intellectual property rights to
which are owned or Controlled, in whole or in part, by IDEC, in either (a) or (b) as of the Effective Date or during the term of the Collaboration Agreement. 

 

	2.22	“Manufacturing Royalties” shall mean the royalties payable by IDEC to third parties for licenses to manufacture or have manufactured Antibody Conjugate
and Non-Antibody Components, for as long as such royalties are payable. The royalties currently payable by IDEC are listed in Exhibit F to the Collaboration Agreement. 

 

	2.23	“Non-Antibody Components” shall mean all components of the Kit other than the Antibody Conjugate. 

 

	2.24.	“Non-Antibody Components Supply Cost” shall mean the invoiced costs and charges of the suppliers of Non-Antibody Components to IDEC together with the
invoiced costs of the Third Party manufacturer for manufacture of Antibody Conjugate from 2B8 provided by IDEC, negotiated at an arm’s-length basis in accordance with the terms of this Supply Agreement. 

 

	2.25	“Non-Conforming Product” shall mean Kits that: (1) do not meet the Specifications; (2) were not manufactured or tested in accordance with the
Quality Control Methods; or (3) were not manufactured in accordance with CGMPs. Only those tests listed in the Specifications may be used to determine conformity. 

 

	2.26	“Party(ies)” shall mean either SCHERING or IDEC and when used in the plural, shall mean both of them. 

 

	2.27	“Quality Control Methods” shall mean those procedures and methods detailed in the Intercompany Quality Agreement between IDEC and SCHERING as
set forth in Exhibit B, as may be amended in writing from time to time by mutual agreement of the Parties hereto, which furthermore shall meet all applicable United States and European Union regulations applicable to the manufacture and
testing of the Licensed Product. 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	4

	2.29	“Regulatory Approval” shall mean any approvals (including pricing and reimbursement approvals), licenses, registrations or authorizations of any
federal, state or local regulatory agency, department, bureau or other governmental entity, necessary 

	 	for the manufacture and sale of a Licensed Product in each regulatory jurisdiction in which the Licensed Product will be sold. 

 

	2.30	“Specifications” means the specifications for the Kits, as set forth in Exhibit A (as may be amended from time to time by mutual agreement of
the Parties within the limit of applicable Regulatory Approvals), which shall meet all applicable United States and European Union governmental rules and regulations relating to manufacturing and testing such as the Current Good Manufacturing
Practices required by the Federal Food, Drug and Cosmetic Act and shall include any other matters agreed between the Parties in writing relating to such Product. 

 

	2.31	“Supply Agreement” means this Supply Agreement between IDEC and SCHERING dated the Effective Date. 

 

	2.32	“Y2B8” means that certain yttrium-labeled monoclonal antibody to B cells more particularly described on Exhibit B to the Collaboration
Agreement. 

 ARTICLE III 
 SUPPLY OF PRODUCT 
  

	3.1	Production of Kits 

During the term of this Supply Agreement and subject to the terms and conditions hereof, IDEC agrees to use all Commercially Reasonable
and Diligent Efforts to supply SCHERING with all of SCHERING’s Clinical Requirements and Commercial Requirements of Kits and Kit Components (hereinafter referred to interchangeably as Kits) for use and sale in the Licensed Territory. During the
term of this Agreement, IDEC will not supply Kits or Kit Components to any Party other than SCHERING for sale or use in the Licensed Territory. During the term of this Agreement, SCHERING will purchase all of its Clinical Requirements and Commercial
Requirements of Kits from IDEC except as otherwise provided in this Supply Agreement. 
  

	3.2	Production of 2B8 

 During
the term of this Supply Agreement, IDEC will manufacture 2B8 for supply to SCHERING at an IDEC facility subject to any limitations in changing location that would be presented by the Intercompany Quality Agreement. IDEC warrants that it has and will
retain sufficient capacity to supply sufficient 2B8 to meet SCHERING’s Clinical Requirements and Commercial Requirements of Kits during the Term of this Supply Agreement. IDEC may not cease supply of 2B8 from IDEC’s facility without
providing at least [***] notice to SCHERING of its decision to cease such supply. In the event that IDEC decides to cease production of 2B8 at IDEC’s Facility, then the provision of Section 7.2 of this Supply Agreement shall apply.

  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	5

 During the term of this Supply Agreement, IDEC will use all Commercially Reasonable and
Diligent Efforts to manufacture 2B8 in a cost-efficient way. IDEC will furthermore use all Commercially Reasonable and Diligent Efforts to reduce the cost of manufacture of the 2B8 as far as reasonably practicable and consistent with the performance
of IDEC’s other obligations hereunder and IDEC’s operation of its manufacturing facility to support its other projects. 
  

	3.3	Supply of Non-Antibody Components 

 IDEC is currently in the course of negotiating a commercial supply agreement with Catalytica for the supply of Non-Antibody Components to meet IDEC’s own requirements in the United States and to meet
SCHERING’s Clinical and Commercial Requirements in the Licensed Territory. IDEC will use all reasonable efforts to negotiate a supply contract with Catalytica on commercially reasonable terms and conditions. IDEC will keep SCHERING informed of
the progress of its negotiations with Catalytica and will take account of all reasonable comments and proposals which SCHERING may make in respect of such supply contracts. 
 IDEC’s agreement with Catalytica shall be such that the terms and conditions do not favor without cause IDEC/United States supply over SCHERING/Licensed Territory supply. Any terms related
specifically to supply in the Licensed Territory shall be subject to SCHERING’s review and approval, where such approval shall not be unreasonably withheld. 
  

	3.4	Supply of Yttrium 

SCHERING may, until such time as it has negotiated a supply agreement with Nordion, Inc. or another Third Party for supply of yttrium in
the Licensed Territory, request IDEC that SCHERING may source some or all of its requirements of yttrium from IDEC under IDEC’s existing agreement with Nordion. IDEC shall accede to such request unless the supply of yttrium to the Licensed
Territory would result in a shortfall of supply to meet IDEC’s requirement in the United States. SCHERING shall reimburse the costs paid by IDEC to Nordion, Inc. for such supply of yttrium, including any additional costs charged by Nordion for
supply to Licensed Territory. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	6

	3.5	Subcontracting 

 Except as
expressly provided in this Supply Agreement, after the EMEA approval, IDEC will not contract out to any Third Party any part of the manufacture or testing of 2B8, Antibody Conjugate, Non-Antibody Components or Kits without the prior written approval
of SCHERING, such approval not to be unreasonably withheld. 
 ARTICLE IV 

FORECASTING 
  

	4.1	Forecasting Procedures 

IDEC will use all reasonable efforts to provide Kits to SCHERING with the longest Kit Expiration Date that is practical under its supply
agreement with Catalytica and any other third parties associated with manufacture of Kits. During the Initial Phase, IDEC shall deliver Kits to SCHERING with a minimum of [***] months or more before Kit Expiration Date. Thereafter, IDEC shall
deliver Kits to SCHERING with a minimum of [***] months or more before Kit Expiration Date. The following provisional forecasting procedures shall apply: 
  

	 	(a)	Within sixty (60) days of the Effective Date, SCHERING will provide IDEC with a firm forecast for Clinical Requirements for the remainder of 1999.

  

	 	(b)	On August 15 of each year starting in 1999 and updated thereafter on the fifteenth day of second month of the calendar quarter (i.e., on 15 November,
15 February, and 15 May) during the term of the Supply Agreement, SCHERING shall provide IDEC with a [***] month rolling forecast of expected Clinical Requirements and Commercial Requirements for Kits for the period between the start of the
following calendar quarter and [***] months thereafter (“the [***] month forecast”). 

  

	 	(c)	The last four (4) quarters of the [***] month forecast (i.e., the four quarters furthest in time from the quarter in which the particular [***] month forecast is
provided by SCHERING) are not binding on SCHERING, and SCHERING shall only be bound to purchase the quantities specified in the first four (4) quarters of the [***] month forecast to the following extent: 

 

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	7

	 	(i)	The quantities specified for delivery in the first and second quarters following the quarter in which the [***] month forecast is submitted are fixed, and SCHERING
shall purchase the amounts specified. The quantity specified in the first and second quarters are referred to as a “Firm Forecast.” 

  

	 	(ii)	 During the Initial Phase, the quantities specified for delivery in the third and fourth quarters following the quarter in which the [***] month
forecast is submitted may be varied by SCHERING by [***] percent [***]. By way of example, if the amount specified in the Initial Phase is 100 units, SCHERING may eventually submit an amended order for up to [***] units or for only [***] units. If
SCHERING wishes to amend an order pursuant to this subsection (ii), it will do so by a quarterly update of the [***] month forecast in such a way that the first and second quarter following the latest quarterly update of the [***] month forecast
will always constitute a Firm Forecast. 

  

	 	(iii)	After the Initial Phase, the quantities specified for delivery in the third and fourth quarters following the quarter in which the [***] month forecast is submitted may
be varied by SCHERING by [***] percent [***]. By way of example, if the amount specified after the Initial Phase is 100 units, SCHERING may submit an amended order for up to [***] units or for only [***] units. If SCHERING wishes to amend an order
pursuant to this subsection (iii), it will do so by a quarterly update of the [***] month forecast in such a way that the first and second quarter following the latest quarterly update of the [***] month forecast will always constitute a Firm
Forecast. 

  

	 	(iv)	The quantities specified for delivery in the first two quarters following the quarter in which the [***] month forecast is submitted are fixed and SCHERING shall
purchase the specified amount. Such quantities specified for the first two quarters shall be referred to as the “Firm Forecast.” 

  

	 	(d)	On November 15 of each year starting in 1999, SCHERING shall provide IDEC a [***] month non-binding forecast on a yearly basis of expected Clinical
Requirements and Commercial Requirements. 

  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	8

	 	(e)	The provisions of this Section 4.1 will be reviewed in good faith by the Parties after the Kit Expiration Date is set by EMEA and the Catalytica Agreement has been
signed. If the agreement with third parties associated with manufacture of Kits, such as Catalytica, provides more flexibility in purchase order and forecasting timing, the Parties will share equitably in this increased flexibility and amend the
forecasting within commercially reasonably parameters and good inventory management practices. 

  

	4.2	Purposes and Firm Forecast Variances 

  

	 	(a)	All forecasts under the Supply Agreement and updates thereof shall be for the sole purpose of assisting IDEC in its planning and will not constitute an obligation on
SCHERING to purchase the quantities of the Kits indicated, except as expressly stated in Section 4.1. Once a forecast has become a Firm Forecast, such Firm Forecast will serve also as a purchase order and SCHERING will specify therein its
desired delivery date. IDEC shall be obligated to ship Kits no more than [***] per year. IDEC shall use Commercially Reasonable and Diligent Efforts to supply to SCHERING any requirements of the Kits in excess of those specified in the Firm
Forecast, but shall not be in breach of the Supply Agreement if it is unable to do so, despite such efforts. 

  

	 	(b)	All Kits supplied by IDEC in terms of the Supply Agreement shall, from the date of receipt by SCHERING, have an unexpired shelf life of at least [***] months during the
Initial Phase and, thereafter, at least [***] months. 

  

	 	(c)	SCHERING may, at its discretion, place orders for Kits or for individual Kit Components or both, for example, SCHERING may order 1000 Kits or may order 1000 units of
Kit Component (1) and 950 units of Kit Component (2). 

 All orders must be placed in terms of specific
numbers of Kits or specific numbers of Kit Components, as the case may be. Quantities actually shipped pursuant to a given purchase order may vary from the quantities reflected in such purchase order by up to five percent (5%) and still be
deemed to be in compliance with such purchase order; provided, however, SCHERING shall only be invoiced and required to pay for the quantities of Kits which IDEC or its designee actually ships to SCHERING, and provided further that SCHERING shall
only be required to pay for such quantities of such Kits, if a certificate of analysis with respect to such Kits accompanies such invoice and indicates that such Kit shipped to SCHERING meets the Specifications. SCHERING shall pay IDEC the amount so
invoiced at the time of IDEC’s shipment of Kits to SCHERING. 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	9

	4.3	Labeling and Packaging of Kits, Finished Product 

 For the Clinical Requirements and Commercial Requirements in the Licensed Territory, SCHERING agrees to exert Commercially Reasonable and Diligent Efforts to perform all work necessary at its expense to
convert Kits supplied by IDEC into finished product, including without limitation, labeling such vials and placing them in [***] packaging for sale, and all related testing and inspection related to the foregoing. 

 

	4.4	Delivery Dates 

 If IDEC expects
a delay in shipment and release of Kits, it shall promptly notify SCHERING of such expected delay and shall use its Commercially Reasonable and Diligent Efforts to minimize such delay. In the event that IDEC cannot deliver Kits to SCHERING within
[***] days after the delivery date specified in a purchase order accepted by IDEC, SCHERING may cancel such portion of such purchase order or accept partial or complete delivery at a later date specified by IDEC. IDEC and/or its designee shall
continue a production and/or vialing campaign until they produce and deliver all quantities of Kits specified in the purchase order and accepted by SCHERING for such campaign period. In the event that the delivery of Kits is delayed by a period in
excess of [***] days, SCHERING may, in addition to any other remedies, without penalty amend the next Firm Forecast by up to an amount equivalent to the delayed shipment. In the event that IDEC cannot deliver the Kits specified in the purchase
order, SCHERING and IDEC shall meet to determine what actions to take and the provisions of Article VI shall apply. 
  

	4.5	Change Orders 

 If
SCHERING requests a change to a SCHERING Firm Forecast order, IDEC shall use Commercially Reasonable and Diligent Efforts to accommodate such change, provided it is reasonable. 

 

	4.6	Kit Shortfall, Supply Interruptions 

  

	 	(a)	The Parties agree to use Commercially Reasonable and Diligent Efforts to carry adequate inventories of Kits for their respective territories. IDEC will use Commercially
Reasonable and Diligent Efforts to carry an adequate inventory of Kits to supply SCHERING. The Kits will be withdrawn from inventory on a First-In First-Out basis and IDEC will use Commercially Reasonable and Diligent Efforts to minimize the age of
the Kits maintained in inventory. 

  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	10

	 	(b)	If, under the Supply Agreement, the Clinical Requirements and Commercial Requirements of SCHERING cannot be met, because of either the quantities of Kits ordered or the
delivery schedules proposed, the Parties acknowledge that Commercial Requirements have priority over Clinical Requirements, except for the Clinical Requirements in the Licensed Territory countries needed to obtain (i) marketing approval of the
Licensed Product in each of such countries for the first indication for the Licensed Product in each of such countries, and (ii) reimbursement approval in the Licensed Territory countries. Once the Licensed Product receives Regulatory Approval
in a given country within the Licensed Territory, the Commercial Requirements will thereafter have priority over Clinical Requirements in such country. 

  

	 	(c)	In the event that for reasons of force majeure or other reasons beyond the control of IDEC there is a temporary reduction in manufacturing capacity resulting in
reduced output of 2B8 or Kits then, and without prejudice to the provisions of Article VI, the supply of Kits will be rationed between SCHERING and IDEC on a basis proportionate to previously prevailing Licensed Product annual turnover in the United
States and Licensed Territory 

  

	4.7	Non-Conforming Kit 

  

	 	(a)	Kits supplied hereunder shall be produced in accordance with the Specifications (see Exhibit A), Quality Control Methods and CGMPs, and shall be stored by IDEC
or its designee until shipment to SCHERING, as appropriate, in accordance with the Specifications prior to any sale or distribution. IDEC shall deliver to SCHERING with each Kit (i) a certificate of analysis indicating such Kits comply with the
Specifications, and (ii) a certificate of compliance indicating that such Kits were manufactured in accordance with CGMPs and indicating non-complying process variances and/or incidents as described in the Intercompany Quality Agreement.

  

	 	(b)	Any non-conforming claim by SCHERING must be submitted to IDEC in writing within [***] days after determining that the Kit is Non-Conforming Product, and be accompanied
by a report (including a fully representative Kit sample from the batch analyzed; provided, however, no Kit sample need be sent if the non-conformance is due to non-compliance with CGMPs) of analysis of the allegedly Non-Conforming Product. If after
IDEC’s own analysis of the Kit sample (which shall be completed within [***] days after its receipt by IDEC) IDEC agrees with the claim of non-conformity and determines that SCHERING is not responsible for the non-conformity, IDEC shall:

  

	 	(i)	Use Commercially Reasonably and Diligent Efforts to promptly replace such Non-Conforming Product; 

 

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	11

	 	(ii)	Fully compensate SCHERING for actual, direct damages sustained as a result of the affected delivery lots of Non-Conforming Product. 

 

	 	(iii)	Reimburse SCHERING for any costs incurred by SCHERING in converting Non-Conforming Product to conforming Kit pursuant to Section (c) below; 

 

	 	(iv)	Pay SCHERING’s actual costs for notification, destruction or return of the Non-Conforming Product; and 

 

	 	(v)	Pay any costs directly associated with the manufacture or distribution of replacement Kits. 

These provisions are without prejudice to any obligations of IDEC under Article XV of the Collaboration Agreement. 

 

	 	(c)	If there are procedures by which SCHERING, without unreasonable effort, inconvenience or expense, can convert, or cause to be converted, any Non- Conforming Product
into conforming Kit, SCHERING shall initiate such procedures upon IDEC’s request, and so long as SCHERING has the necessary regulatory authority to do so. If IDEC is responsible for the non-conformity and SCHERING converts the Non-Conforming
Product into conforming Kit, then such Kit shall be deemed to be conforming Kit delivered hereunder on the date on which such conversion is completed and IDEC shall reimburse SCHERING the reasonable costs of converting the Non-Conforming Product
into conforming Kit. 

  

	 	(d)	If, after its own analysis, IDEC does not agree with the claim of non-conformity or determines that SCHERING is responsible for the non-conformity, SCHERING and IDEC
shall in good faith promptly attempt to agree upon a settlement of the issue as described in the Intercompany Quality Agreement. If a decision is not reached under the Intercompany Quality Agreement the Parties may use the Dispute Resolution
Provisions in Article V to allocate the economic loss, if any, associated with SCHERING’s disposition of the Kits or finished product. 

  

	 	(e)	IDEC shall replace the allegedly Non-Conforming Product during: 

  

	 	(i)	The pendency of any settlement negotiations described in subsection (d) of this Section; or 

 

	 	(ii)	The exhaustion of procedures specified in subsections (b), (c), and (d) of this Section if the inability to use the allegedly Non-Conforming Product causes a
shortfall of available Kits or finished product to meet the Clinical Requirements or the Commercial Requirements. 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	12

	4.8	Shipment 

 IDEC shall ship
the Kits to such destinations chosen by SCHERING to the extent that such shipments are permitted by law and practical for IDEC given the regulatory requirements of the United States and the importing country. Such shipments shall be by carriers
acceptable to SCHERING. Shipment shall be F.O.B (as defined in the latest version of INCOTERMS from time to time in force) IDEC San Diego or the site of IDEC’s designee, provided that IDEC’s designee is located in the United States or the
European Union. Title and risk of loss as to all Kits shipped shall pass to SCHERING upon delivery to the carrier. SCHERING shall be responsible for all freight, freight brokerage, insurance and other costs attributable to shipping the Kits from the
manufacturing site to any destination chosen by SCHERING. 
  

	4.9	Governing Terms 

 All
sales of Kits from IDEC to SCHERING shall be subject to the provisions of the Supply Agreement, including the Specifications, and shall not be subject to any terms and conditions contained on any Firm Forecasts or purchase orders submitted under the
Supply Agreement, except insofar as any such Firm Forecasts or purchase orders establishes in writing: (i) the quantity of any Kits ordered; (ii) the delivery date, consistent with the terms hereof; (iii) the shipment routes; or
(iv) the carrier selected by SCHERING. 
  

	4.10	Taxes 

 SCHERING
purchasing Kits hereunder shall bear all applicable federal, provincial, municipal and other governmental taxes (such as sale, use or similar taxes), duties, or import charges, except for any tax on profits that IDEC may be required to pay or
collect as a result of the Supply Agreement. 
  

	4.11	No Implied Representations, Warranties or Conditions 

 IDEC warrants that each of the Kits supplied by IDEC shall meet the Specifications (see Exhibit A), and shall be manufactured according to CGMPs. and in accordance with the provisions of the
Inter-Company Quality Agreement. EXCEPT AS OTHERWISE EXPRESSLY HEREIN PROVIDED, IDEC MAKES NO REPRESENTATIONS OR WARRANTIES AND THERE ARE NO CONDITIONS, EXPRESS OR IMPLIED, STATUTORY OR OTHERWISE, WITH RESPECT TO THE KITS SUPPLIED HEREUNDER,
INCLUDING, WITHOUT LIMITATION, ANY SUCH REPRESENTATIONS, WARRANTIES OR CONDITIONS WITH RESPECT TO THE NON-INFRINGEMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OF SUCH KITS OR FINISHED PRODUCT. 

 

  

					
	IDEC/Schering AG Supply Agreement 9 June 1999	  		  	13

 ARTICLE V 
 PAYMENTS AND INVOICES 
  

	5. 1	Payment for Clinical Requirements and Commercial Requirements 

  

	 	(a)	Clinical Requirements. IDEC will supply all Clinical Requirements of Kits, which are used in clinical studies for obtaining all Regulatory Approvals in the
Licensed Territory at [***] of Cost of Goods Sold. 

  

	 	(b)	Commercial Requirements. The Parties good faith estimate of Cost of Goods Sold is [***] per Kit. Assuming that only one such Kit is necessary per patient
therapeutic protocol (i.e., elimination of the Imaging Step), IDEC shall supply SCHERING with Commercial Requirements at up to [***] of IDEC’s Cost of Goods Sold up to [***] per Kit (“Cost Plus Maximum Price”). Above the Cost Plus
Maximum Price, IDEC will supply Commercial Requirements at [***] of Cost of Goods Sold. In the event that any regulatory authorities in the Licensed Territory approves Licensed Product with a label requiring the majority of patients to use two such
Kits (including the Imaging Step) per patient therapeutic protocol, IDEC shall supply SCHERING with Commercial Requirements at up to [***] of IDEC’s Cost of Goods Sold up to [***] per two Kits (“Two Kits Cost Plus Maximum Price”)
above the Two Kit Cost Plus Maximum Price, IDEC will supply Commercial Requirements at [***] of Cost of Goods Sold. 

  

	5.2	Invoices and Method of Payment 

  

	 	(a)	For the first calendar year or part thereof during which Kits are purchased by SCHERING from IDEC hereunder (the “First Purchase Year”), the purchase price of
Kits and Kit Components will be based on a good faith assessment by IDEC , taking account of all available knowledge and experience, of the likely actual Costs of Goods Sold of the Kit in the First Purchase Year. Within three months of the end of
the First Purchase Year, IDEC will notify SCHERING of the actual Cost of Goods Sold of Kits supplied during the First Purchase Year and the purchase price will be retroactively adjusted. Each Party shall pay any sums owing to the other Party as a
result of such adjustment within four (4) weeks of notification by the other Party of the amount due. The purchase price of the Kit for the calendar year following the First Purchase Year (such year and every succeeding calendar year being
referred to as a “Purchase Year”) will be calculated on the basis of the actual Cost of Goods Sold of Kits in the First Purchase Year and will be retroactively adjusted within three months of commencement of the next Purchase Year and the
same procedure will be followed for each Purchase Year of the Supply Agreement. 

  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	14

	 	(b)	IDEC shall prepare an invoice for each shipment of Kits setting forth the purchase price, broken down into Antibody Manufacturing Cost, Cost of Non-Antibody Components
and Third Party Royalties. All payments to be made hereunder shall be made within thirty (30) days in U.S. dollars by bank wire transfer in immediately available funds to such account as IDEC shall designate before such payment is due, free and
clear of any taxes, duties, levies, fees or charges, except for withholding taxes due on behalf of the seller (to the extent applicable). SCHERING shall make any withholding payments due on behalf of IDEC and shall promptly provide IDEC with written
documentation of any such payment sufficient to satisfy the reasonable requirements of an appropriate tax authority with respect to an application by the selling Party for a foreign tax credit for such payment or for similar treatment.

  

	5.3	Audits 

 SCHERING shall
have the right once per calendar year to request that its independent public accounting firm perform an audit of IDEC’s books of accounts for the sole purpose of verifying the calculations of Cost of Goods Sold in accordance with the Supply
Agreement. Such audits will be conducted at the expense of SCHERING; provided, however, that if the audit results in an adjustment of greater than [***] percent [***] for Cost of Goods Sold in any period, the cost of the audit will be borne by
IDEC. Audit results will be shared with both Parties. Audits are limited to results in the two (2) years prior to audit notification. 
 ARTICLE VI  
 ALTERNATE SUPPLY 

 

	6.1	Non-Antibody Components 

After the Supply Agreement between IDEC and Catalytica expires or is terminated (provided that the earliest termination date is no later
than five years following Regulatory Approval of Licensed Product in Licensed Territory, SCHERING shall be entitled to have its requirements of Non-Antibody Components supplied by an alternate supplier. SCHERING shall have the right to equip and
qualify itself, an Affiliate, or a third party for the manufacture of Non-Antibody Components provided that SCHERING gives IDEC [***] months notice of its decision to switch suppliers, and provided further that IDEC does not have any reasonable
objective grounds to object to such supplier. 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	15

	6.2	Alternate Supply of Antibody Conjugate 

  

	 	(a)	Whenever IDEC anticipates that it will be unable to supply those quantities of Antibody Conjugate necessary to meet SCHERING’s Clinical Requirements or Commercial
Requirements, as the case may be, IDEC shall promptly notify SCHERING of such anticipated inability. SCHERING shall be relieved of its obligation to purchase its requirements of Antibody Conjugate exclusively from IDEC during the period of
IDEC’s inability to supply. 

  

	 	(b)	In the event (a) that IDEC should be unable to supply those quantities of Antibody Conjugate necessary to meet SCHERING’s Clinical Requirements or Commercial
Requirements, as the case may be, for a period exceeding [***]months; or (b) IDEC notifies SCHERING of its decision to cease production of Antibody Conjugate at IDEC’s Facility; or (c) IDEC is no longer selling Licensed Product in the
United States and the Cost of Goods Sold plus [***] for Kits (or, if the imaging step is required, the Cost of Goods Sold plus [***]) is greater than [***] times the price per Kit that SCHERING can document with a binding contract manufacturing
bid based on good faith arms length negotiations,; in each such case SCHERING shall be relieved of its obligation to purchase Antibody Conjugate solely from IDEC and IDEC shall cooperate with SCHERING and any alternative supplier designated by
SCHERING to allow such alternative supplier to meet SCHERING’s Clinical Requirements and Commercial Requirements of Antibody Conjugate, including the provision of a royalty-free license under any manufacturing technology of IDEC. SCHERING
warrants that it will secure all the licenses necessary to manufacture Licensed Product. 

 ARTICLE VII

 DISPUTE RESOLUTION 
  

	7.1	Disputes 

  

	 	(a)	The Parties recognize that disputes as to certain matters may from time to time arise during the term of the Supply Agreement which relate to the Parties’ rights
and/or obligations hereunder. It is the objective of the Parties to establish procedures to facilitate the resolution of disputes arising under the Supply Agreement in an expedient manner by mutual cooperation and without resort to litigation. To
accomplish this objective, the Parties agree to follow the procedures set forth in this Article VII, if and when a dispute arises under the Supply Agreement. 

 

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	16

	 	(b)	Any unresolved disputes arising hereunder shall be first referred to the Steering Committee under the Collaboration Agreement by any Party at any time after such
dispute has arisen and such Party believes that there has been sufficient discussion of the matter at levels below the Steering Committee. If the Steering Committee is unable to resolve such dispute within [***] days of being requested by a
Party to resolve a dispute, any Party may, by written notice to the other, have such dispute referred to their respective chief operating officers, for attempted resolution by good faith negotiations within [***] days after such notice is
received. In the event the designated operating officers are not able to resolve such dispute, any Party may at any time after the [***] day period invoke the provisions of Section 7.2 

 

	7.2	Mediation and Arbitration 

The Parties agree that any dispute, controversy or claim (except as to any issue relating to intellectual property owned in whole or in
part by IDEC or SCHERING) arising out of or relating to the Supply Agreement, or the breach, termination, or invalidity thereof, shall be resolved through negotiation, mediation and/or binding arbitration. If a dispute arises between the Parties,
and if said dispute cannot be resolved pursuant to Section 7.1, the Parties agree to first try in good faith to resolve such dispute by mediation administered by the American Arbitration Association in accordance with its Commercial Mediation
Rules. If efforts at mediation are unsuccessful within [***] days, any unresolved controversy or claim between the Parties shall be resolved by binding arbitration in accordance with the Commercial Arbitration Rules of the American Arbitration
Association, except as modified herein. Each Party shall select one arbitrator to resolve the dispute. The arbitration decision shall be rendered within six months of conclusion of mediation and shall be binding and not be appealable to any court in
any jurisdiction. The prevailing Party may enter such decision in any court having competent jurisdiction. The mediation or arbitration proceeding shall be conducted in New York, New York. The Parties agree that they shall share equally the cost of
the mediation/arbitration filing and bearing fees, and the cost of the mediator/arbitrator. Each Party must bear its own attorney’s fees and associated costs and expenses. 

 

	7.3	Jurisdiction 

 For the
purposes of this Article VII, the Parties agree to accept the jurisdiction of the federal courts located in the Southern District of New York for the purposes of enforcing awards entered pursuant to this Article and for enforcing the agreements
reflected in this Article. 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	17

 ARTICLE VIII  

TERM AND TERMINATION 
  

	8.1	Term and Termination 

 The
Supply Agreement shall commence as of the Effective Date and continue in full force and effect until the Collaboration Agreement is terminated or expires subject to any ongoing obligations provided for in the Collaboration Agreement, which shall
apply also to the Supply Agreement. 
  

	8.2	Termination for Breach 

This Agreement may be terminated (i) in its entirety by either Party in the event of the material breach or default by the other
Party of the terms and conditions hereof or (ii) with respect to the 2B8 or the Antibody Conjugate or any Non-Antibody Components in the event of the material breach or default by the other Party of the terms and conditions hereof with respect to
the 2B8 or the Antibody Conjugate or the Non-Antibody Components as the case may be, provided however that the other Party shall first give to the defaulting Party written notice of the proposed termination or cancellation of this Agreement,
specifying the grounds therefor. Upon receipt of such notice, the defaulting Party shall have sixty (60) days to respond by curing such default or by delivering to the other Party a certificate that such breach is not capable of being cured
within such sixty (60) days and that the breaching Party is working diligently to cure such breach, but in no event shall the time period for curing such breach exceed an additional thirty (30) days. If the breaching Party does not so
respond or fails to cure the breach within the additional time set forth above, then the other Party may terminate this Supply Agreement, either in its entirety or with respect to 2B8 or the Antibody Conjugate or the Non-Antibody Components, as the
case may be. Termination of this Supply Agreement pursuant to this Section 8.2 shall not affect any other rights or remedies which may be available to the non-defaulting Party and shall not effect termination of the Collaboration Agreement.

  

	8.3	Consequences of Termination 

 In the event of termination by SCHERING pursuant to Section 8.2 above, the provisions of Section 14.5(c) of the Collaboration Agreement shall apply. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	18

 ARTICLE IX  

MISCELLANEOUS 
  

	9.1	Notices 

 All notices and
demands required or permitted to be given or made pursuant to the Supply Agreement shall be in writing and given: (i) immediately upon personal delivery or facsimile transmission to the Parties to be notified, (ii) one (1) day after
deposit with a commercial overnight courier with tracking capabilities, or (iii) five (5) days after deposit with the United States Postal Service, by registered or certified mail, postage prepaid and properly addressed to the address of the
Party to be notified as shown below: 
  

			
	       to IDEC:	  	 Corporate Secretary
 IDEC
Pharmaceuticals Corporation
 11011 Torreyana Road
 San Diego, CA 92121

		
	       with copies to:	  	 President
 Facsimile: 01
(858) 550-8750

		
	       to SCHERING:	  	 Schering A.G.
 13342 Berlin,
Germany
 Facsimile: 011 49 30 4681 4086

 or to such other address as to which either Party may notify the other in accordance with this Section.
Any notice sent by facsimile shall be followed within 24 hours by a signed notice sent by overnight courier. 
  

	9.2	Force Majeure 

 Neither
Party shall lose any rights hereunder or be liable to the other Party for damages or losses on account of failure of performance by the defaulting Party if the failure is occasioned by government action, war, fire, earthquake, explosion, flood,
viral, bacterial, or mycoplasm contamination of Licensed Product with no assignable cause for any such contamination after FDA mandated inspection by IDEC, strike, lockout, embargo, act of God, or any other cause beyond the control of the defaulting
Party, whether or not of the kind listed in the foregoing examples, provided that the Party claiming force majeure has exerted all reasonable efforts to avoid or remedy such force majeure; provided, however, that in no event shall a
Party be required to settle any labor dispute or disturbance. To the extent one Party is unable to perform its obligations hereunder due to a force majeure event described in the preceding sentence and the other Party is commercially able to do so
(the “Able Party”“), the Able Party shall use its Commercially Reasonable and Diligent Efforts to perform the obligations of the Unable Party for appropriate compensation so long the Unable Party is affected by the force majeure
event. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	19

	9.3	Assignment 

 The Supply
Agreement shall be binding upon and inure to the benefit of the Parties, their successors and permitted assigns. Neither Party may assign the Supply Agreement without the prior written consent of the non-assigning Party, which consent shall not be
unreasonably withheld; provided, however, either Party may assign, without consent of the other Party, all of its rights and obligations under the Supply Agreement in connection with a merger or similar reorganization or the sale of all or
substantially all of its assets, or otherwise with the prior written consent of the other Party. The Supply Agreement shall survive any such merger or reorganization of either Party with or into, or such sale of assets to, another party and no
consent for such merger, reorganization or sale shall be required hereunder. 
  

	9.4	Waiver 

 Except as
specifically provided for herein, the waiver from time to time by either of the Parties of any of their rights or their failure to exercise any remedy shall not operate or be construed as a continuing waiver of same or of any other of such
Party’s rights or remedies provided in the Supply Agreement. 
  

	9.5	Severability 

 If any
term, covenant or condition of the Supply Agreement or the application thereof to any Party or circumstance shall, to any extent, be held to be invalid or unenforceable, then (i) the remainder of the Supply Agreement, or the application of such
term, covenant or condition to Parties or circumstances other than those as to which it is held invalid or unenforceable, shall not be affected thereby and each term, covenant or condition of the Supply Agreement shall be valid and be enforced to
the fullest extent permitted by law; and (ii) the Parties hereto covenant and agree to renegotiate any such term, covenant or application thereof in good faith in order to provide a reasonably acceptable alternative to the term, covenant or
condition of the Supply Agreement or the application thereof that is invalid or unenforceable, it being the intent of the Parties that the basic purposes of the Supply Agreement are to be effectuated. 

 

	9.6	Governing Law 

 The Supply
Agreement shall be governed by and construed in accordance with, the laws of the State of California without giving effect to principles of conflict of laws or the United Nations Convention on Contracts for the International Sale of Goods.

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	20

	9.7	Ambiguities 

 Ambiguities,
if any, in the Supply Agreement shall not be construed against any Party, irrespective of which Party may be deemed to have authored the ambiguous provision. 
  

	9.8	Counterparts 

 The Supply
Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. 

 

	9.9	Conflicts with Collaborations Agreement 

 To the extent that there is any conflict between any of the terms of the Supply Agreement and any of the terms of the Collaboration Agreement, the terms of the Supply Agreement shall govern. 

 

	9.10	Entire Agreement 

 Except
for those agreements expressly identified in the Supply Agreement, the Supply Agreement, including all Exhibits attached hereto which are hereby incorporated herein by reference, sets forth all the covenants, promises, agreements, warranties,
representations, conditions and understandings between the Parties hereto regarding the subject matter hereof. No subsequent alteration, amendment, change or addition to the Supply Agreement shall be binding upon the Parties hereto unless reduced to
writing and signed by the respective authorized officers of the Parties. 
  

	9.11	Accrued Rights, Surviving Obligations 

 Termination, relinquishment or expiration of the Supply Agreement for any reason shall be without prejudice to any rights that shall have accrued to the benefit of either party prior to such
termination, relinquishment or expiration, including damages arising from any breach hereunder. Such termination, relinquishment or expiration shall not relieve either Party from obligations under Sections 4, 11, Article VII, Sections 8.3, 9.3, 9.4,
9.5, 9.6, 9.7, 9.9, 9.10, and 9.11 herein, and any other obligations which are expressly indicated to survive the termination or expiration of the Agreement. 

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	21

 IN WITNESS WHEREOF, the Parties have executed the Supply Agreement effective on the date first set forth
above. 
  

									
	SCHERING AKTIENGESELLSCHAFT	 		 	IDEC PHARMACEUTICALS CORPORATION
					
	By:	 	

	 		 	By:	 	

	Title:	 	MEMBER OF BOARD OF EXECUTIVE DIRECTORS	 		 	Title:	 	CHIEF OPERATING OFFICER
	Date:	 	9th June 1999	 		 	Date:	 	JUNE 9, 1999

  

			
	
		
	By	 	

	Title	 	HEAD OF STRATEGIC BUSINESS UNIT THERAPEUTICS
		
	Date	 	9th June 1999

  

			
	IDEC/Schering AG Supply Agreement 9 June 1999	  	22

 EXHIBIT A 
 Specifications 
 Current specifications are provisional and
will be established upon completion of the 1999 BLA-enabling campaigns 

 TABLE 10 
 IDEC-2B8-MX-DTPA KIT COMPONENT 
 RELEASE TESTING AND SPECIFICATIONS 

[***] 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

 TABLE 11 
 FORMULATION BUFFER 
 RELEASE TESTING AND SPECIFICATIONS 

[***] 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

 TABLE 12 
 50 Mm SODIUM ACETATE 
 RELEASE TESTING AND SPECIFICATIONS 

[***] 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

 TABLE 13 
 REACTION VIAL 
 RELEASE TESTING AND SPECIFICATIONS 

[***] 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

 EXHIBIT B 
 Intercompany Quality Agreement 

 INTERCOMPANY QUALITY AGREEMENT 

Between IDEC Pharmaceuticals Corporation and Schering A.G.  

TABLE OF CONTENTS 
  

			
	 1.      QUALITY AGREEMENT
	  	
	 1.1 Purpose
	  	
	 1.2 Relationship to Supply Agreement
	  	
	 1.3 The Products
	  	
		
	 2.      QUALITY CONTACTS
	  	
		
	 3.      MANUFACTURING CGMP COMPLIANCE
	  	
	 3.1 General
	  	
	 3.2 Facilities
	  	
	 3.3 CGMP Compliance
	  	
	 3.4 Master Controlled Documents
	  	
	 3.5 Manufacturing Processes
	  	
	 3.6 Lot Numbers
	  	
	 3.7 Dates of Manufacture and Expiration
	  	
	 3.8 Storage and Shipment
	  	
		
	 4.      QUALITY CONTROL
	  	
	 4.1 General
	  	
	 4.2 CGMP Compliance
	  	
	 4.3 Master Controlled Documents
	  	
	 4.4 Raw Materials and Components
	  	
	 4.5 In-Process and Product Testing
	  	
	 4.6 QC Action Limits and Specifications
	  	
	 4.7 Retain Samples
	  	
	 4.8 Stability Program
	  	
	 4.9 Contract QC Laboratories
	  	
	 4.10 Out-of-Specification (OOS) Investigations
	  	
		
	 5.      QUALITY ASSURANCE
	  	
	 5.1 General
	  	
	 5.2 CGMP Compliance
	  	
	 5.3 Master Controlled Documents
	  	
	 5.4 Variance Investigations
	  	
	 5.5 Lot Disposition
	  	
	 5.6 Product Complaints
	  	
	 5.7 Product Recalls
	  	
	 5.8 Records Retention
	  	
	 5.8 QA Presence in the Manufacturing Facility
	  	

  

			
	Quality Agreement 9 June 1999	  	i

			
	 6. REGULATORY CMC COMPLIANCE
	  	
	 6.1 Regulatory Compliance Inspections
	  	
	 6.2 Right to Audit
	  	
	 6.3 Audit Closeout
	  	
		
	 7. DISPUTE RESOLUTION
	  	
	 7.1 Non-Conformity Dispute
	  	
	 7.2 Test Result Dispute
	  	
		
	 8. CHANGE MANAGEMENT
	  	
	 8.1 Controlled Documentation
	  	
	 8.2 Change Control
	  	
		
	 9. ANNUAL PRODUCT REVTEW
	  	
		
	 10. MANUFACTURING PROCESS CHANGE REPORT
	  	
		
	 11. CMC REGULATORY FILING SUPPORT
	  	

  

			
	Quality Agreement 9 June 1999	  	ii

	1.	QUALITY AGREEMENT 

  

	 	1.1	Purpose 

 This agreement
defines the roles, responsibilities and interactions between the Quality Departments of IDEC PHARMACEUTICALS CORPORATION (herein called “IDEC”) and SCHERING AG (herein called “SCHERING”). 

 

	 	1.2	Relationship to Supply Agreement 

 This agreement shall be incorporated within and constitute a part of the Supply Agreement between the two companies. Terms defined in the Supply Agreement and used in this Agreement shall have the
meanings attributed to them in the Supply Agreement unless expressly stipulated to the contrary. 
  

	 	1.3	The Products 

 The
PRODUCTS covered by this agreement are described in the Supply Agreement and include 2B8; the Antibody Conjugate; the Non-Antibody Components; and the Kits, all of which are referred to collectively in this Intercompany Quality Agreement as the
PRODUCTS. 
  

	2.	QUALITY CONTACTS 

Emergency contact names and numbers, during and outside working hours, for the heads of Quality at each company: 

John Geigert 

Vice President, Quality, IDEC 
  

	 	Work:	(858) 550-8641 

	 	Home:	(760) 943-6986 

Dr. Anneliese Fehse-Jonas 
 Head of Quality Control, SCHERING, 
  

	 	Work:	0049 30 4681 2526 

	 	Home:	0049 30 3616 723 

 The IDEC and
SCHERING Quality Departments will jointly establish a list of Quality contacts in order to conduct their business. 

  

			
	Quality Agreement 9 June 1999	  	1

	3.	MANUFACTURING CGMP COMPLIANCE 

  

	 	3.1	General 

 The
manufacturing operations for the PRODUCTS are defined in the Supply Agreement. 
  

	 	3.2	Facilities 

  

	 	3.2.1	IDEC will manufacture 2B8 at an IDEC facility. Catalytica Pharmaceuticals or another designee so designated by IDEC (under contract to IDEC) and agreed to by SCHERING
will manufacture the Antibody Conjugate from 2B8 supplied by IDEC and the Non-Antibody Components at its Greenville, North Carolina site. 

  

	 	3.2.2	The premises and equipment used to manufacture the Kit Components will be according to current regulatory requirements and in accordance with Regulatory Approvals and
in accordance with the controlled documentation approved by IDEC and agreed with SCHERING. 

  

	 	3.2.3	IDEC shall not be entitled to make a change in the facility that will impact the manufacture of the PRODUCTS from a regulatory compliance standard or which would
otherwise have an adverse impact on SCHERING in Licensed Territory without the prior written consent of SCHERING, such consent not to be unreasonably withheld. 

 

	 	3.2.4	The production of the PRODUCTS will be conducted in a suitably controlled environment and such facilities will be regularly monitored for parameters critical to the
process (e.g., temperature, room pressures, viable and non-viable particles) to demonstrate compliance with CGMP guidelines and any conditions registered in the manufacturing authorization. 

 

	 	3.2.5	Controlled access will be maintained to the premises. All visitors must sign-in and are escorted during any visit to the areas of the premise used to manufacture, test,
and store the PRODUCTS. 

  

	 	3.3	CGMP Compliance 

 The
principles detailed in the US Current Good Manufacturing Practices (21 CFR 200, 211, and 600) and “The Rules Governing Medicinal Product in The European Community—Volume IV Good Manufacturing Practice for Medicinal Products” CGMP
Guidelines will cover the standards of manufacture of the PRODUCTS, including any applicable product license requirements. 

  

			
	Quality Agreement 9 June 1999	  	2

	 	3.4	Master Controlled Documents 

  

	 	3.4.1	IDEC is responsible for ensuring that master batch records are in place for all manufacturing operations related to the PRODUCTS. 

 

	 	3.4.2	IDEC is responsible for ensuring that SOPS required to manufacture the PRODUCTS, and to support CGMPS, are in place. 

 

	 	3.4.3	Changes to these controlled documents will be handled as outlined by Change Management (see Section 8). 

 

	 	3.5	Manufacturing Processes 

  

	 	3.5.1	IDEC is responsible for ensuring that all equipment, computer, utility and facility qualification and validation activities associated with the manufacture of the
PRODUCTS are in place. 

  

	 	3.5.2	IDEC is responsible for ensuring that the manufacturing processes for the PRODUCTS are validated. 

 

	 	3.5.3	IDEC is responsible for ensuring that adequate cleaning is carried out between lots of different products to prevent contamination, and that there are established
cleaning limits for product changeover. 

  

	 	3.6	Lot Numbers 

 IDEC is
responsible for ensuring that “Lot Identification Numbers” for all PRODUCTS are in place, and will provide a unique identifier to each lot. 
  

	 	3.7	Dates of Manufacture and Expiration 

  

	 	3.7.1	Date of Manufacture 

 The Date
of Manufacture will be defined in master production records. 
  

	 	3.7.2	Expiration Date 

 IDEC,
consistent with regulatory agency approval, will set the expiry period for the PRODUCTS. 
 The Expiration Date will be
calculated from the Date of Manufacture using the approved expiry period. The Expiration Date will be the last day of the month computed above. 

  

			
	Quality Agreement 9 June 1999	  	3

	 	3.8	Storage and Shipment 

  

	 	3.8.1	Storage 

 IDEC, consistent with
regulatory agency approval, will set the storage conditions for the PRODUCTS. 
  

	 	3.8.2	Shipment 

 Any shipment of the
PRODUCTS requires prior written consent by IDEC Quality. This authorization will be on a lot by lot basis. 
  

	4.	QUALITY CONTROL 

  

	 	4.1	General 

 The QC testing
activities for the PRODUCTS are divided by contract between IDEC and Catalytica. In general, IDEC is responsible for testing activities related to the 2B8 and the Antibody Conjugate. In general, Catalytica is responsible for testing activities
related to the sodium acetate buffer component, the formulation buffer component and the reaction vial component. Notwithstanding any such division of responsibility, IDEC remains solely responsible to SCHERING for all QC testing of PRODUCTS.

  

	 	4.2	CGMP Compliance 

 The
principles detailed in the US Current Good Manufacturing Practices (21 CFR 200, 211, and 600) and “The Rules Governing Medicinal Product in The European Community—Volume IV Good Manufacturing Practice for Medicinal Products” CGMP
Guidelines will cover the standards of QC for the PRODUCTS, including the product specifications and any applicable product license or pharmacopoeia or formulatory requirements. 

 

	 	4.3	Master Controlled Documents 

  

	 	4.3.1	IDEC is responsible for ensuring that master controlled documents are in place for all QC operations (e.g., laboratory operations, sampling plans, test methods,
specifications and stability protocols) related to the PRODUCTS. 

  

	 	4.3.2	Changes to these controlled documents will be handled as outlined by Change Management (see Section 8). 

  

			
	Quality Agreement 9 June 1999	  	4

	 	4.4	Raw Materials and Components 

  

	 	4.4.1	IDEC is responsible for ensuring that approved suppliers for raw materials and components used in the manufacture of the PRODUCTS are in place.

  

	 	4.4.2	IDEC is responsible for ensuring that qualification of the approved raw material suppliers is in place. 

 

	 	4.4.3	IDEC is responsible for ensuring that only chemical materials, packaging and labeling components, approved within the master production records, are used.

  

	 	4.5	In-Process and Product Testing 

  

	 	4.5.1	IDEC is responsible for ensuring that all required QC in-process and product testing is carried out using the sampling plans, test methods and specifications listed in
master controlled documents. 

  

	 	4.5.2	IDEC will qualify reference standards, and will work with SCHERING to ensure that an adequate supply is available for SCHERING’s use if needed. Financial liability
for supplying SCHERING with such standards shall be at SCHERING’s expense. 

  

	 	4.5.3	SCHERING may perform testing to confirm IDEC provided test results, at their expense. Dispute resolutions in conflicting test data will be handled per Section 7.

  

	 	4.5.4	Should regulatory agencies require SCHERING to perform on-site QC testing for the PRODUCTS, IDEC will work with SCHERING to transfer the relevant test methods and
validate the assays at the new site. Financial liability for these activities shall be at SCHERING’s expense. 

  

	 	4.6	QC Action Limits and Specifications 

  

	 	4.6.1	Each in-process QC test will have an action limit assigned and each product release QC test will have a specification assigned. 

 

	 	4.6.2	Changes to these controlled action limits and specifications will be handled as outlined by Change Management (see Section 8). 

 

	 	4.7	Retain Samples 

  

	 	4.7.1	Retain Samples – Excipients Used in Final Formulations 

 IDEC will ensure that retain samples of the excipients used in the final formulations are held for at least six (6) years beyond the expiry period of the Licensed Products in which used. The amount
of sample retained will be twice the quantity required to carry out all of the tests required to determine if the material meets its specifications, with the exception of sterility and pyrogen testing. (21 CFR 211.170a) 

  

			
	Quality Agreement 9 June 1999	  	5

	 	4.7.2	Retain Samples – PRODUCTS 

IDEC will ensure that it retains samples of the PRODUCTS are held for at least six (6) years beyond the expiry period. The amount of
sample retained will be four times the quantity required to carry out all of the tests required to determine if the material meets its specifications, with the exception of sterility and pyrogen testing. (21 CFR 211.170b) SCHERING will be granted
access to half of the retained samples for SCHERING’s own analysis. 
  

	 	4.8	Stability Program 

  

	 	4.8.1	IDEC is responsible for ensuring that a routine stability testing program for the PRODUCTS is in place. 

 

	 	4.8.2	The stability program will be in compliance with regulatory agency commitments. 

 

	 	4.8.3	The stability program will generally follow ICH guidelines. 

  

	 	4.8.4	Any confirmed problems that arise as a result of the stability program will be communicated promptly to SCHERING by IDEC. 

 

	 	4.9	Contract QC Laboratories 

  

	 	4.9.1	IDEC is responsible for ensuring the compliance of any QC laboratories that may be contracted to perform testing of the PRODUCTS or materials used in the manufacture of
the PRODUCTS. 

  

	 	4.9.2	IDEC will have an agreement with each contract testing laboratory that permits access by regulatory agency inspectors and IDEC auditors.

  

	 	4.10	Out-of-Specification (OOS) Investigations 

  

	 	4.10.1	IDEC is responsible for ensuring that the appropriate investigation is carried out for any testing that fails to meet specification. 

 

	 	4.10.2	Each investigation will be reviewed and approved by IDEC, and will follow the current procedures recommended by regulatory agencies. 

  

			
	Quality Agreement 9 June 1999	  	6

	5.	QUALITY ASSURANCE 

  

	 	5.1	General 

 The QA
activities for the PRODUCTS are divided by contract between IDEC and Catalytica. In general, IDEC is responsible for QA activities related to the 2B8 and the Antibody Conjugate. In general, Catalytica is responsible for QA activities related to
sodium acetate buffer component, the formulation buffer component, and the reaction vial component. IDEC has absolute responsibility for release of the PRODUCTS. 
  

	 	5.2	CGMP Compliance 

 The
principles detailed in the US Current Good Manufacturing Practices (21 CFR 200, 211, and 600) and “The Rules Governing Medicinal Product in The European Community – Volume IV Good Manufacturing Practice for Medicinal Products” CGMP
Guidelines will cover the standards of QA for the PRODUCTS, including any product license requirements. 
  

	 	5.3	Master Controlled Documents 

  

	 	5.3.1	IDEC is responsible for ensuring that master controlled documents are in place for all QA operations (e.g., investigations, auditing, lot release protocols) related to
the PRODUCTS. 

  

	 	5.3.2	Changes to these controlled documents will be handled as outlined by Change Management (see Section 8). 

 

	 	5.4	Variance Investigations 

  

	 	5.4.1	IDEC will ensure that any variance (deviation) that arises from either the process during manufacture or testing the PRODUCTS is carefully explained and documented in
the records, justified and approved by Quality Assurance. 

  

	 	5.4.2	Any QC in-process action limit (see Section 4.6.1) that is exceeded will be treated as a variance. 

 

	 	5.4.3	IDEC will notify SCHERING if any problems are discovered during the investigation of a variance that may impact the PRODUCTS lot(s) previously shipped.

  

	 	5.5	Lot Disposition 

  

	 	5.5.1	Release of the PRODUCTS for further labeling and distribution by SCHERING is the absolute responsibility of IDEC Quality. 

  

			
	Quality Agreement 9 June 1999	  	7

	 	5.5.2	For each lot released, IDEC will provide SCHERING a copy of the Certificate of Analysis (COA) and a Certificate of Compliance (COC). 

 

	 	5.5.3	Certificate of Analysis (COA): This document will include the name of the PRODUCTS, the lot number and the date of manufacture. The COA will list the In-Process QC
tests performed, action limits and actual test results. The COA will also list the product release QC tests performed, specifications and actual test results. 

 

	 	5.5.4	Certificate of Compliance (COC): This document will attest to the fact that the lot of PRODUCTS was made in accordance with all applicable regulations, product
licenses, and company policies. This document will include the lot quantity approved, the lot yield, and the expiration date. It will also include a listing of all manufacturing variances and/or incidents for the lot that have been adjudicated

  

	 	5.5.5	The separate Kit Components will be minimally identified by size and the distinct color of caps or such reasonable identifiers requested by SCHERING.

  

	 	5.6	Product Complaints 

  

	 	5.6.1	IDEC is responsible for receiving and initially investigating any Licensed Products complaints in the United States. 

 

	 	5.6.2	IDEC will notify SCHERING promptly, in any case within five (5) Business Days, of any product complaints received, SCHERING will respond in writing with
five (5) business days, and IDEC will provide SCHERING in writing the results of the investigation within thirty (30) business days. 

  

	 	5.6.3	SCHERING is responsible for receiving and initially investigating any Licensed Products complaints in the Licensed Territory. 

 

	 	5.6.4	SCHERING will notify IDEC promptly, in any case within five (5) Business Days, of any product complaints received, IDEC will respond in writing within five
(5) business days, and SCHERING and will provide IDEC in writing the results of the investigation within thirty (30) business days. 

  

	 	5.6.5	IDEC will send SCHERING a listing of all product complaints received during the preceding year in respect of the Licensed Product by the end of February in each year.

  

	 	5.6.6	SCHERING will send IDEC a list of all product complaints received during the preceding year in respect of the Licensed Product by the end of February in each year.

  

			
	Quality Agreement 9 June 1999	  	8

	 	5.7	Product Recalls 

  

	 	5.7.1	IDEC is responsible for instituting a Licensed Product recall in the United States due to any defect considered sufficiently serious. 

 

	 	5.7.2	IDEC will notify SCHERING within 24 hours of any recall of the Licensed Product, and will work closely with SCHERING on any proposed corrective actions.

  

	 	5.7.3	SCHERING is responsible for instituting a Licensed Product recall in the Licensed Territory due to any defect considered sufficiently serious. 

 

	 	5.7.4	SCHERING will notify IDEC within 24 hours of any recall of the Licensed Product, and will work closely with IDEC on any proposed corrective actions.

  

	 	5.7.5	Before any product recall is carried out, the drug safety manager of SCHERING or IDEC as the case may be will notify his counterpart of the reason for the withdrawal.

  

	 	5.7.6	Without prejudice to the provisions of Article XV of the Collaboration Agreement or any other remedies available to SCHERING, where such Product Recall has been caused
by any breach by IDEC of its obligations under the Collaboration Agreement, the Supply Agreement or the Intercompany Quality Agreement, then IDEC shall pay all of SCHERING’s actual costs for notification, destruction or return of the units of
Licensed Product recalled and pay any costs directly associated with the manufacture or distribution of replacement Licensed Product. SCHERING may also, without penalty, amend the Firm Forecast for the six months following the date of the Product
Recall to take account of such Product Recall. 

  

	 	5.8	Records Retention 

  

	 	5.8.1	IDEC is responsible for ensuring that records are kept of equipment usage (previous product produced in non-dedicated equipment), of cleaning, and of any
maintenance/calibration performed. 

  

	 	5.8.2	IDEC is responsible to ensure that lot production records and testing records are maintained for the PRODUCTS for the expiry date of the PRODUCTS plus one year, at a
minimum. 

  

	 	5.9	QA Presence in the Manufacturing Facility 

 IDEC is responsible for ensuring that adequate QA presence occurs in the manufacturing facility during the manufacture of the PRODUCTS to ensure compliance with CGMPs. 

  

			
	Quality Agreement 9 June 1999	  	9

	6.	REGULATORY CMC COMPLIANCE 

  

	 	6.1	Regulatory Compliance Inspections 

  

	 	6.1.1	IDEC will inform SCHERING with as much advance notice as possible of any regulatory inspections that may involve the PRODUCTS and shall, where possible, provide
SCHERING with the opportunity to observe the inspection closeout session, if requested. 

  

	 	6.1.2	IDEC also agrees to notify SCHERING promptly of any written or oral inquiries, notifications or inspection activity by any governmental entity (or any third party
authorized by a governmental entity) in regard to any of the PRODUCTS. IDEC shall furnish to SCHERING promptly copies of any report or correspondence issued by the governmental entity (or a third party authorized by a governmental entity) in
connection with such visit or inquiry, including but not limited to any FDA Form 483 (List of Inspectional Observations) or warning letter or equivalents thereto from the EMEA or other regulatory authority in the Licensed Territory and copies of all
responses or explanations relating to items set forth above, in each case purged only of trade secrets or other confidential or proprietary information of IDEC that are unrelated to the obligations under this Agreement or the Supply Agreement and
are unrelated to the PRODUCTS 

  

	 	6.1.3	IDEC shall notify SCHERING of any other production issues or other information of which IDEC becomes aware which may affect the regulatory status of the PRODUCTS.

  

	 	6.1.4	IDEC agrees to promptly rectify or resolve any deficiencies noted by a governmental entity (or a third party authorized by a governmental entity) in a report or
correspondence issued to IDEC and which are relevant to IDEC’s performance under this Agreement or the Supply Agreement or the Collaboration Agreement. 

 

	 	6.1.5	IDEC will inform SCHERING sufficiently in advance of any CMC commitment to a regulatory agency resulting from an inspection regarding the PRODUCTS. SCHERING will be
given the opportunity to comment on the proposed response to regulatory agencies in the Licensed Territory. IDEC will give due consideration to SCHERING’s comments, provided the comments are received by IDEC within time commitments needed to
address regulatory concerns. 

  

	 	6.1.6	SCHERING has the right to perform an inspection at IDEC or at any third party engaged in manufacturing or testing Kit Components subject to limitations of
Section 6.2. IDEC will also cooperate in any inspection required by any European or Japanese regulatory authority. 

  

			
	Quality Agreement 9 June 1999	  	10

	 	6.2	Right to Audit 

  

	 	6.2.1	IDEC will allow representatives from SCHERING to have access to manufacturing, warehousing, laboratory premises and records at IDEC for audit purposes listed below in
6.2.2 and 6.2.3. SCHERING representatives will be escorted at all times by IDEC personnel. 

  

	 	6.2.2	IDEC will permit SCHERING to conduct for cause investigative audits to address material PRODUCT quality or safety problems. 

 

	 	6.2.3	IDEC will permit SCHERING to perform one standard GMP compliance audit per year in those years which IDEC is conducting a manufacturing campaign. A thirty day written
notice to IDEC is required to permit scheduling. 

  

	 	6.2.4	SCHERING auditing of Third Party contracted operations (e.g., Catalytica) will occur only under IDEC’s lead and consistent with contractor’s policies.

  

	 	6.3	Audit Closeout 

  

	 	6.3.1	An exit meeting will be held with representatives from SCHERING and IDEC to discuss significant audit observations. 

 

	 	6.3.2	SCHERING will provide a written report of all observations to IDEC. IDEC will provide a written response to all findings. 

 

	7.	DISPUTE RESOLUTION 

  

	 	7.1	Non-Conformity Dispute 

In the event that a dispute arises between SCHERING and IDEC in the non-conformity of a lot of the PRODUCTS, the heads of Quality, or
their delegated representatives, from both companies will in good faith promptly attempt to reach an agreement. 
  

	 	7.2	Test Result Dispute 

  

	 	7.2.1	In the event that a dispute arises between SCHERING and IDEC in the testing performed by SCHERING for the PRODUCTS, the resolution will proceed in stages. The first
stage requires direct communication between analysts from both parties to determine that the methods of analysis are the same and are being executed in the same manner at both sites. Second, carefully controlled and split samples should be sent from
one site to another in an attempt to reach agreement. Should there be a failure to achieve resolution, analysts from both parties will be required to meet to work through the analysis of a mutually agreeable sample. If these actions fail to
achieve resolution, and only after these avenues have been exhausted, a qualified referee laboratory will be used to achieve resolution. This laboratory must be agreeable to both parties prior to use. The results from this referee laboratory will be
used as final authority to determine responsibilities. 

  

			
	Quality Agreement 9 June 1999	  	11

	 	7.2.2	In the event that the heads of Quality are unable to resolve the dispute within thirty days, the Parties shall select an independent testing laboratory acceptable to
both parties to perform an analysis of nonconformity and render a decision on the responsible party. The decision of such independent testing laboratory shall be final and binding on the Parties. In the event the independent testing laboratory
determines the dispute in SCHERlNG’s favor, the costs of the testing laboratory will be borne by IDEC. In the event that the independent testing laboratory determines the dispute in IDEC’s favor, the costs of the testing laboratory will be
borne by SCHERING. 

  

	8.	CHANGE MANAGEMENT 

  

	 	8.1	Change Consent 

 Upon
filing of the Market Authorization Application (MAA) in the Licensed Territory, IDEC agrees that no changes will be made to any materials, specifications, equipment or methods of production or sites of production or testing of any PRODUCTS without
SCHERlNG’s prior written approval, such approval not to be unreasonably withheld. Subsequent to such approval of SCHERING, IDEC may then make such approved changes in manufacturing procedures so long as, in any event, (i) such changes are
permitted by applicable governmental regulations and the terms of any licenses, registrations, authorizations or approvals previously granted by the applicable governmental entity with respect to such PRODUCTS, and (ii) SCHERING receives copies
of all documentation relating to such approved changes. If the changes require the additional license, registration, authorization or approval of any applicable governmental entity in the Licensed Territory, IDEC may not implement the changes until
it receives written notice from SCHERING that the governmental entity has authorized the change. IDEC shall cooperate fully with SCHREING in preparing, and will provide all necessary data and information for, a submission requesting prior
authorization or approval of a change in materials, specifications, equipment, locations or methods of production or testing of the PRODUCTS. 
  

	 	8.2	Controlled Documentation 

  

	 	8.2.1	All manufacturing, testing and storage operations performed for the PRODUCTS will have IDEC Quality review and written approval. 

  

			
	Quality Agreement 9 June 1999	  	12

	 	8.2.2	The Quality Departments of IDEC and SCHERING will determine which of these controlled documents also require a SCHERING Quality review and written approval.

  

	 	8.3	Change Control 

  

	 	8.3.1	Changes to the controlled documents or to validated equipment and systems specific to the PRODUCTS must have an IDEC Quality written approval and the approval of
SCHERING, such approval not to be unreasonably withheld, prior to implementation. 

  

	 	8.3.2	Changes to the controlled documents will be consistent with regulatory agency notification requirements. 

 

	9.	ANNUAL PRODUCT REVIEW 

 IDEC is responsible for ensuring that an Annual Product Review for the PRODUCTS is prepared, per 21 CFR 211.180(e). This report will cover all manufacturing, testing and storage activities. It will be a
review of any changes at in the manufacturing, testing, storage or validation of the PRODUCTS in the previous calendar year and a summary of lots made, released, and rejected. Also, control charting or trend analysis of key product parameters will
be performed. Any abnormalities will be explained in the annual review. 
 SCHERING will receive, no later than ten
(10) business days after signature of the report, five (5) copies thereof. 
  

	10.	MANUFACTURING PROCESS CHANGE REPORT 

 IDEC is responsible for ensuring that an Annual Manufacturing Process Change Report is prepared, per 21 CFR 601.12(d). 
  

	11.	CMC REGULATORY FILING SUPPORT 

  

	 	11.1	Each Party shall promptly notify the other of new regulatory requirements of which it may become aware which are relevant to the manufacture, testing and storage of the
PRODUCTS, and shall confer with each other with respect to the best means to comply with such requirements. 

  

	 	11.2	If a manufacturing process change or release requirement is required by a regulatory agency, each Party shall provide reasonable technical and regulatory assistance to
support any necessary regulatory filings that the filing party will make to obtain regulatory approval. Financial liability for such changes shall be at SCHERING’s expense, if such change if required in the Licensed Territory.

  

			
	Quality Agreement 9 June 1999	  	13

  
 

 
  

			
	December 16, 2004	  	VIA FEDERAL EXPRESS

 Schering A.G. 

13342 Berlin, Germany 
 To Whom It May Concern:

 This letter shall serve as an amendment to that certain Supply Agreement between Biogen Idec Inc. (formerly IDEC
Pharmaceuticals Corporation) and Schering Aktiengesellschaft, dated as of June 9, 1999 (the “Agreement”). Capitalized terms used in this letter, but not otherwise defined, shall have the meanings given them in the Agreement. Except as
otherwise specifically set forth in this letter, all provisions of the Agreement remain in full force and effect. 
  

	 	1.	The Agreement is hereby amended so that during the period beginning retroactively on January 1, 2002 and ending December 31, 2004, Section 2.13 shall be
amended and restated as follows: 

 “2.13 “Cost of Goods Sold” shall mean the total of
(i) $[***] per Kit and (ii) [***].” 
  

	 	2.	The Agreement is hereby amended so that during the period beginning January 1, 2005 and ending December 31, 2009, Section 2.13 shall be amended and
restated as follows: 

 “2.13 “Cost of Goods Sold” shall mean the total of (i) $[***]
per Kit and (ii) [***]; provided, that during any calendar year, if (a) a Triggering Event has occurred, (b) the average sum of the [***] and the [***] for all Kits ordered by Schering during such calendar year is less than $[***] per
Kit and (c) Biogen Idec determines in its sole discretion that the Cost of Goods Sold should be adjusted retroactively for such calendar year and thereafter, the Cost of Goods Sold shall be adjusted retroactively for such calendar year and
prospectively to reflect such average sum. The applicable costs for each of the four Kit Components shall be set forth in each invoice delivered to Schering by Biogen Idec.” 
 Biogen Idec 5200 Research Place San Diego, CA 92122 Phone 858 401 8000 www.biogenidec.com 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

	 	3.	The Agreement is hereby amended to add a new Section 2.33 as follows: 

 “2.33 “Triggering Event” shall mean (i) a material change in the manufacturing process of the Kits that requires FDA approval, (ii) a change in the manufacturing site for
the Kits or a Kit Component or (iii) a material increase in the volume of Kits manufactured by Biogen Idec in a calendar year. 
  

	 	4.	Section 5.1(b) of the Agreement is hereby amended and restated as follows: 

 

	 	“(b)	Commercial Requirements. BIOGEN IDEC will supply all Commercial Requirements to SCHERING at BIOGEN IDEC’s Cost of Goods Sold. 

 

	 	5.	The Agreement is hereby amended to add a new Section 5.1(c) as follows: 

 

	 	“(c)	Training Kits. If and when available for distribution, BIOGEN IDEC will supply all training Kits for clinical and commercial purposes to SCHERING free of charge;
provided that under no circumstance shall BIOGEN IDEC have an obligation to manufacture Kits for such purpose. SCHERING agrees to pay for the shipping costs thereof. 

 

	 	6.	Section 5.2(a) of the Agreement is hereby amended and restated as follows: 

 

	 	“(a)	During the term of this Agreement, the purchase price of Kits and Kit Components will be BIOGEN IDEC’s Cost of Goods Sold. In the event that the Cost of Goods Sold
is retroactively adjusted at the end of a calendar year (as provided for in Section 2.13 hereof), it shall be so adjusted within three (3) months following the end of the calendar year for which an adjustment is made.

  

	 	7.	The first sentence of Section 5.2(b) of the Agreement is hereby amended and restated as follows: 

 

	 	“(b)	BIOGEN IDEC shall prepare an invoice for each shipment of Kits setting forth each component of BIOGEN IDEC’s Cost of Goods Sold for such Kits.”

 In addition to the foregoing, the Parties agree to engage in good faith discussions
regarding an amendment to the Agreement beginning on January 1, 2007, to fix, for the period beginning on January 1, 2010, a mutually agreeable cap on the sum of the [***] and the [***] components for the Cost of Goods Sold. If the Parties
fail to fix a mutually agreeable cap on the sum of the [***] and the [***] components for the Cost of Goods Sold, then, until such a mutually agreeable cap is fixed by the Parties, the “Cost of Goods Sold” for the period commencing on
January 1, 2010 shall mean the lesser of: (1) the sum of $[***] per Kit, plus [***], or (2) the sum of the [***], plus the [***], plus [***]. 
 If you agree with the foregoing, please sign in the space provided below and return an original to me at your convenience. 

 

	
	Sincerely,
	
	

	 Edward Rodriguez
 Vice
President

  

	
	 Acknowledged and Agreed

	
	

	 Schering A.G.

  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

 AMENDMENT TO SUPPLY AGREEMENT 

This Amendment to the Supply Agreement (this “Amendment”) is made effective as of the 16th day of January, 2012 by and between
Biogen Idec US Corporation, a Massachusetts corporation (“Biogen Idec”), and Bayer Pharma AG, a German corporation f/k/a Schering Aktiengesellschaft (“Bayer”). Biogen Idec and Bayer are sometimes
referred to herein individually as a “Party” and collectively as “Parties”. 

RECITALS 
 A. IDEC
Pharmaceuticals Corporation and Schering Aktiengesellschaft entered into a Collaboration & License Agreement dated 9 June 1999, as amended on 13 July 2004 and 16 September 2005 (the “Collaboration
Agreement”), relating to the development and commercialization of a product now known as Zevalin. 
 B. Pursuant to the
Collaboration Agreement, IDEC Pharmaceuticals Corporation agreed to supply Schering Aktiengesellschaft with its requirements of Zevalin and, as such, the Parties entered into a Supply Agreement dated 9 June 1999, as amended on 14 December
2004 (the “Supply Agreement”). 
 C. IDEC Pharmaceuticals Corporation is now known as Biogen Idec Inc. and Schering
Aktiengesellschaft is now known as Bayer Pharma AG. 
 D. Effective as of 1 July 2011, Biogen Idec Inc. assigned all of its rights and
obligations under the Supply Agreement to Biogen Idec, which is an Affiliate of Biogen Idec Inc. The parties wish to document Bayer’s consent to such assignment. 
 E. The Parties wish to amend the Supply Agreement. Biogen Idec Inc. and Bayer are concurrently herewith superseding and replacing the Collaboration Agreement with an Amended and Restated License Agreement
between such parties (the “License Agreement”); provided, however, that the Collaboration Agreement shall continue to apply with respect to events or activities occurring prior to the date hereof. 

F. Bayer has agreed, subject to the terms and conditions of this Amendment, to release Biogen Idec of its supply obligations pursuant to the
Collaboration Agreement and the License Agreement. 
 NOW, THEREFORE, THE PARTIES AGREE AS FOLLOWS: 

1. Capitalized terms used in this Amendment without definition shall have the same meanings ascribed to them in the Supply Agreement and, as applicable,
the License Agreement. This Amendment shall be deemed to be Bayer’s written consent to the assignment of the Supply Agreement described in Recital D above. 

 2. Unless terminated earlier in accordance with its terms, the Supply Agreement shall expire on
December 31, 2014. Following such expiration, Biogen Idec shall have no further supply-related obligations pursuant to the Supply Agreement, the Collaboration Agreement or the License Agreement (including, without limitation, supplying Kits or
manufacturing 2B8) other than as set forth in Sections 7 and 8 below (i.e., manufacturing transfer activities) and Articles II, VII and IX of the Supply Agreement. Termination, relinquishment or expiration of the Supply Agreement for
any reason shall be without prejudice to any rights that have accrued to the benefit of either Party prior to such termination, relinquishment or expiration (including, without limitation, damages arising from any breach thereunder). 

3. This Amendment shall become effective only upon Biogen Idec Inc. and Bayer entering into the License Agreement. If the License Agreement is not
entered into, then this Amendment shall be of no force or effect. 
 4. The Parties agree that the Cost of Goods Sold shall be US $[***] per Kit
plus [***] and shall remain fixed until the expiration of the Supply Agreement (i.e., December 31, 2014); provided, however, that the Cost of Goods Sold shall be US $[***] per Kit for each Kit ordered for delivery between [***]
and [***] so long as such Kits can be supplied from inventory of Kits existing when such order is submitted. 
 5. Notwithstanding that
the Supply Agreement requires the supply of Kits, prior to expiration or earlier termination of the Supply Agreement and upon Bayer’s written request no later than [***], Biogen Idec agrees to conduct a single drug substance manufacturing
campaign in [***] (at any time during [***] within [***] months of such written request) to supply Bayer with a quantity of 2B8 (i.e., the antibody) as Bayer orders to meet its anticipated requirements for the period following expiration or
earlier termination of the Supply Agreement. Bayer shall make such a written request pursuant to a single purchase order sent in a manner and format consistent with Biogen Idec’s reasonable direction and made in batch quantities for batches
produced using the 2,000 liter bioreactors in Biogen Idec’s Cambridge, MA facility. The price of such 2B8 shall be US $[***] per gram of active weight antibody for the first batch ordered and US $[***] per gram of active weight antibody for any
additional batches ordered. Sections 4.7 (Non-Conforming Kit), 4.8 (Shipment), 4.9 (Governing Terms), 4.10 (Taxes) and 4.11 (No Implied Representations, Warranties or Conditions) and Article V (Payments and Invoices) shall apply with respect to any
such 2B8 ordered pursuant to this Section 5 mutatis mutandis; provided, however, that payment for the price for each ordered batch shall be due and payable in [***] equal annual installments beginning on [***] and each
anniversary thereof. Notwithstanding the foregoing, if Bayer assigns the Supply Agreement as contemplated by Section 6 below, then the price for each ordered batch (or, if applicable, the remaining installments for the price of each
ordered batch) shall be paid in advance by the applicable assignee as a condition to such assignment; provided, however, that if such assignment occurs before such campaign, then the applicable assignee shall deposit funds for such
advance payment into an escrow account with an escrow agent reasonably acceptable to Biogen Idec (it being understood that any escrow agreement, joint instructions or other terms of escrow release shall provide for the immediate release of funds to
Biogen Idec upon delivery of any such 2B8 ordered pursuant to this Section 5).  
 6. In accordance with Section 9.3 of
the Supply Agreement but subject to Section 5 above, Biogen Idec hereby consents to the assignment by Bayer of the Supply Agreement to any Third Party to whom (i) Bayer sublicenses all or substantially all of its rights in the
Licensed Product pursuant to Section 5.2 the License Agreement or (ii) Bayer assigns all of its rights and obligations under the License Agreement pursuant to Section 13.1(b) of the License Agreement. 

 

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  
 - 48 -

 7. Bayer acknowledges that Biogen Idec anticipates subcontracting and/or transitioning analytical services
and fill/finish activities prior to [***] and conjugation activities during [***]. Pursuant to Section 3.5 of the Supply Agreement, Bayer hereby consents to such subcontracting and/or transitioning subject to the following: 

(a) Bayer shall submit any and all applicable regulatory submissions to the appropriate regulatory authority in all jurisdictions for the
Licensed Territory as soon as reasonably possible for the subcontracting and/or transitioning contemplated by this Section 7 and otherwise no later than six (6) months after completion of the applicable validation. 

(b) Conjugation activities by the applicable contract manufacturing organization shall be validated using the 2B8 supplied to Bayer
pursuant to Section 5 above. Biogen Idec shall be responsible for the costs of the applicable validation batch or batches (including, without limitation, the contract manufacturing organization’s cost of the campaign itself), except
that Bayer shall pay Biogen Idec US $[***] per gram of active weight antibody used to produce Antibody Conjugate for the first batch and US $[***] per gram of active weight antibody used to produce Antibody Conjugate for any additional batches (it
being understood that each batch will use a minimum of 17.8 grams of active weight antibody and that Bayer will only pay for that active weight antibody used to produce commercially usable Antibody Conjugate). Notwithstanding any provision herein to
the contrary, the Parties acknowledge and agree that Biogen Idec shall have no further responsibility with respect to such Antibody Conjugate upon completion of the validation campaign. 

(c) Biogen Idec shall use commercially reasonable efforts to engage a single contract manufacturing organization for the analytical
services and the fill/finish activities, and Biogen Idec shall use commercially reasonable efforts to engage the same contract manufacturing organization for the conjugation activities. The identity of each contract manufacturing organization shall
be subject to Bayer’s prior consent, such consent not to be unreasonably withheld, conditioned or delayed. 
 (d) Biogen
Idec shall cause any subcontract with any such contract manufacturing organization(s) to allow for its assignment to Bayer following the expiration or earlier termination of the Supply Agreement. The duration of any such subcontract shall commence
prior to expiration or earlier termination of the Supply Agreement and shall be for a term that is typical for the type of agreement in question but, in any event, no less than [***] years. In negotiating any such subcontract, Biogen Idec shall
negotiate in good faith to obtain commercially reasonable terms and conditions taking into account that such subcontract will be assigned to Bayer. Biogen Idec shall assign to Bayer, and Bayer shall assume from Biogen Idec, each such subcontract as
soon as reasonably possible after the expiration or earlier termination of the Supply Agreement (it being understood that Bayer shall enter into an assignment and assumption agreement for each such subcontract in form and substance reasonably
acceptable to both Biogen Idec and Bayer). 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  
 - 49 -

 Bayer acknowledges and agrees that Biogen Idec’s obligations under this Section 7 are
dependent upon Bayer’s timely performance of its obligations under this Section 7. Biogen Idec recognizes and accepts that the obligations of this Section 7 shall survive expiration or earlier termination of the Supply
Agreement to the extent such obligations are consistent with the manufacturing transfer activities contemplated by Section 8 below. 

8. On expiration or earlier termination of the Supply Agreement, Biogen Idec and Bayer shall exercise fair dealing and negotiate in good faith to agree
upon a project plan (the “Project Plan”) describing the activities required to effect an orderly transition of the manufacture of 2B8 (i.e., the antibody) and related conjugation activities for the Licensed Territory from Biogen
Idec to Bayer or its designee, and the Parties shall subsequently implement the Project Plan. Without prejudice to the generality of the foregoing, the Project Plan shall include or address the following: 

(a) the cost and expense of Biogen Idec’s personnel and resources used in connection with the implementation of the Project Plan will
be borne by Biogen Idec; 
 (b) Biogen Idec delivering or providing access to Bayer or its designee of documentation reasonably
necessary to effect such transition in an orderly manner consistent with regulatory requirements, including documentation summarizing any BIOGEN IDEC Know-How; 
 (c) if Bayer requests, Bayer or its designee obtaining the same rights as Biogen Idec Inc.’s rights under that certain Amended and Restated Non-Exclusive License Agreement, dated as of
December 20, 2007, by and between Genentech, Inc. and Biogen Idec Inc. (which is commonly referred to by Biogen Idec as its “Cabilly license”) in connection with the manufacture of the Licensed Product for the Licensed Territory
through a direct license from Genentech, Inc. to Bayer or its designee or, if a direct license cannot be achieved after the use of commercially reasonable efforts, a sublicense from Biogen Idec Inc. to Bayer or its designee (it being understood that
Bayer or its designee shall enter into a sublicense agreement for such sublicense in form and substance reasonably acceptable to both Biogen Idec and Bayer); and 
 (d) limitations on the type, number, frequency and length of meetings, document requests and the like, as well as procedures and timelines with the aim of efficiently using Biogen Idec’s personnel
and resources and otherwise minimizing cost and expense in connection therewith. 
  

  
 - 50 -

 In furtherance of the foregoing, Biogen Idec’s obligations under the Project Plan shall be limited to
(i) providing appropriate answers to specific, reasonable questions only during normal business hours and (ii) no more than a total of [***] person-days of time, in the aggregate for all participation, by all Biogen Idec personnel.
Bayer acknowledges and agrees that Biogen Idec’s obligations under this Section 8 are limited in accordance with the Project Plan and are dependent upon (x) the reasonable competence of Bayer or its designee with respect to the
activities at issue (including, without limitation, obtaining the required approvals in a timely manner for the conduct of manufacturing activities at a facility selected and prepared by Bayer or its designee and possession by Bayer or its designee
of the requisite skills, equipment, ingredients and resources for the manufacture of product similar to the Licensed Product) and (y) Bayer’s timely performance of its obligations under Section 7 above, this
Section 8 and the Project Plan. Notwithstanding any provision herein to the contrary, the Parties acknowledge and agree that Biogen Idec shall be obligated to participate in the manufacturing transfer activities contemplated by this
Section 8 only once and that, subject as stated below, Biogen Idec shall have no further responsibility with respect to such activities thereafter. In the event that such transition is not successfully achieved through no fault of Biogen
Idec or Bayer, Biogen Idec agrees to provide reasonable additional assistance if requested by Bayer, provided that Bayer shall pay for any costs and expenses associated with such additional assistance. Such costs and expenses shall be reasonable and
shall be directly referable to the activities to be performed. Biogen Idec recognizes and accepts that the obligations of this Section 8 shall survive expiration or earlier termination of the Supply Agreement. 

Except for the Cabilly license referred to above, Biogen Idec represents and warrants that, as of the date of this Amendment and to its knowledge, no
other license from a Third Party is required for the manufacture of the Licensed Product for all indications in the Field. 
 9. Except as
expressly amended by this Amendment, the Supply Agreement remains in full force and effect. 
 10. This Amendment shall be binding upon and
inure to the benefit of the Parties and their respective successors and assigns. This Amendment may be executed in separate counterparts, each of which shall be deemed an original and all of which together shall constitute one and the same
instrument. Signatures on counterparts of this Amendment transmitted by facsimile or e-mail shall be deemed effective for all purposes. 
 [SIGNATURE PAGE FOLLOWS] 
  

	[***]:	CONFIDENTIAL PORTIONS OMITTED AND FILED SEPARATELY WITH THE COMMISSION. 

  
 - 51 -

 IN WITNESS WHEREOF, the Parties have executed and delivered this Amendment by their duly authorized
officers and representatives as of the date hereof. 
  

									
	BIOGEN IDEC US CORPORATION	 		 	BAYER PHARMA AG
					
	By:	 	 /s/ George A. Scangos
	 		 	By:	  	 /s/ F. Gardyan-Eisenlohr

	Name:	 	George A. Scangos	 		 	Name:	  	F. Gardyan-Eisenlohr
	Title:	 	CEO	 		 	Title:	  	General Counsel
					
		 		 		 	By:	  	 /s/ Andreas Fibig

		 		 		 	Name:	  	Andreas Fibig
		 		 		 	Title:	  	Title IllegibleEX-10.16

 Exhibit 10.16 
 LICENSE AGREEMENT 
 THIS AGREEMENT, effective this 23rd day of May, 2006,
between Merck Eprova AG, a Swiss corporation organized and existing under the laws of Switzerland and with its principal place of business at Im Laternenacker 5, 8200 Schaffhausen, Switzerland (“EPRO”), and Spectrum Pharmaceuticals,
Inc., a Delaware corporation with its principal place of business at 157 Technology Drive, Irvine, California 92688, United States (“Spectrum”). EPRO and Spectrum may hereinafter each be referred to as a Party or collectively as the
Parties. 
 W I T N E S S E T H, That: 

WHEREAS, EPRO has certain technical information and patent rights relating to the Licensed Technology (as hereinafter defined);

 WHEREAS, Targent, Inc., a Delaware corporation (“Targent”) and EPRO had entered into a License Agreement
regarding the Licensed Technology. 
 WHEREAS, Spectrum has acquired from Targent all rights and assets regarding the
Licensed Technology and EPRO gives its consent to a transfer of such rights and assets from Targent to Spectrum. 

WHEREAS, Spectrum desires to obtain such license under the Licensed Technology to undertake development of the Licensed Product
for commercialization in the Territory in the Field of Use (all foregoing capitalized terms as hereinafter defined) after receipt of approval from the Food and Drug Administration for the Licensed Product, and to have EPRO manufacture the active
pharmaceutical ingredient (“API”) of Licensed Product for Spectrum the same pursuant to the terms of a Manufacturing and Supply Agreement executed by EPRO and Spectrum as soon as practicable the terms of which shall be negotiated in good
faith (the “Manufacturing and Supply Agreement”). 
 NOW, THEREFORE, in consideration of the promises and the
mutual covenants herein contained, and other good and valuable consideration, the receipt of which are acknowledged by the Parties, the Parties agree as follows: 
 ARTICLE I - DEFINITIONS 
 As used in this Agreement the following terms,
whether singular or plural, shall have the following meanings: 
 A. “Affiliate” shall mean any entity that owns or
controls or is owned or controlled by a Party through ownership of more than fifty percent (50%) of the stock entitled to vote for election of directors of that Party or the maximum percentage of stock interest that a foreign investor may own,
whether fifty percent or less, pursuant to the local laws, regulations or administrative orders of any country, provided the party exercises a substantial control of general policy of the company. 

 B. “Confidential Information” shall mean information ancillary to the Licensed
Technology, as further defined in Article III. 
 C. “Documents” shall mean the regulatory filings made in the
Territory related to the Licensed Technology, including, but not limited to, IND #32,487, NDA #’s 20-140 and 20-141 and the related orphan drug designations. 

D. “Effective Date” shall mean the date indicated first above as the effective date of this Agreement.

 E. “FDA” shall mean the United States Food and Drug Administration, or any successor agency thereto. 

F. “Field of Use” shall mean all uses in the field of oncology. 

G. “GAAP” shall mean generally accepted accounting principles in the United States or International Accounting Standards
outside the United States, in each case as consistently applied by Spectrum, its Affiliates or its Sublicensees in their respective financial statements, audited if applicable. 

H. “Improvements” shall mean one or more enhancements, improvements or modifications in the manufacture, formulation,
ingredients, preparation, dosage, administration or packaging of a License Product or the Licensed Technology made during the term of this Agreement. 
 I. “IND” shall mean (i) an Investigational New Drug application as defined in the United States Food, Drug & Cosmetic Act and applicable regulations promulgated thereunder, as
amended from time to time or (ii) an equivalent application or filing with the applicable regulatory authority in any country other than the United States allowing the commencement of human clinical trials. 

J. “License” shall mean the license granted pursuant to Article II of this Agreement. 

K. “Licensed Know-How” shall mean any technical or manufacturing information and data, methods, processes, drawings,
inventions, formulas, data on safety and efficacy, patent applications, trade secrets materials, models, designs, prototypes or samples, relating to all forms (including but not limited to both the injectable and oral forms) of Levofolinic Acid as
either the free acid or in any salt form, including any information, data, or other materials necessary or useful for the submission to the appropriate U.S. regulatory authorities by Spectrum to obtain the registration or approval of the Licensed
Product. 

  
 2 

 L. “Licensed Patents” shall mean those patents and patent applications in
existence as of the Effective Date and listed in Exhibit A, and any divisions, re-issues, continuations and continuations-in-part or their equivalents, and the foreign equivalents thereof. 

M. “Licensed Product” shall mean any product in any form (including but not limited to both the injectable and oral forms)
made, have made, used, sold, or otherwise disposed of: 
  

	 	i)	which is covered by the Licensed Technology; 

  

	 	ii)	the manufacture of which requires use of the Licensed Technology; or 

  

	 	iii)	which would, but for the License granted herein, otherwise directly infringe, contributorily infringe or induce the infringement of any of the Licensed Patents.

 N. “Licensed Technology” shall mean the Licensed Patents and the Licensed Know-How of EPRO.

 O. “Net Sales” shall mean with respect to any period for any country in the Territory, the gross receipts, by
Spectrum (for purposes of this Article I (O), the term “Spectrum” shall include Third Parties used by Spectrum to market the Licensed Product) its Affiliates or its Sublicensees, as applicable, from unrelated third parties for sales of
Licensed Product, less the following deductions if actually allowed and allocable to Licensed Product: (i) discounts, credits, rebates, allowances, adjustments, rejections, recalls, and returns for which the customer has been credited;
(ii) trade, quantity, or cash discounts or rebates customary to the industry and actually allowed, given or accrued (including, but not limited to, cash, governmental and managed care rebates, hospital or other buying group charge backs, and
governmental taxes in the nature of a rebate based on usage levels or sales of the Licensed Product); (iii) sales, excise, turnover, inventory, value-added, and similar taxes assessed on the sale of the Licensed Product; (iv) an
allowance for actual transportation, distribution, importation, insurance and other handling fees; (v) sales, transfers or dispositions of Licensed Product for charitable, promotional (including samples), pre-clinical, clinical or
regulatory purposes will be excluded from Net Sales, as will sales or transfers of Licensed Product among Spectrum and it’s Affiliates, and Sublicensees. For the avoidance of doubt, for each Licensed Product the Net Sales shall be calculated
only once for the first sale of such Licensed Product by Spectrum, its Affiliate or its Sublicensees, as the case may be, to a Third Party which is neither an Affiliate or Sublicensee of Spectrum. A sale of Licensed Products by Spectrum, its
Affiliate or its Sublicensees to a wholesaler, distributor or any other Third Party shall be regarded as the first sale of the Licensed Product for the purpose of calculating Net Sales. Net Sales shall not include the amount received on account of
sales of a Licensed Product or of sales of a Licensed Product in a particular country for which the term of this Agreement has expired. 

  
 3 

 P. “NDA” shall mean a New Drug Application, as defined in the United States Food,
Drug & Cosmetic Act and applicable regulations promulgated thereunder, as amended from time to time, to obtain approval from the FDA for commercial sale of a Licensed Product. 

Q. “Regulatory Exclusivity Period” shall mean any period of data, market or other regulatory exclusivity, including any such
periods listed in the FDA’s Orange Book. 
 R. “Sublicensee” shall mean any Third Party granted a sublicense by
Spectrum of no greater scope than granted by EPRO to Spectrum, whose identity shall be disclosed confidentially by Spectrum to EPRO prior to the execution of such Sublicense. EPRO shall have the right to approve or disapprove such Sublicensee within
ten (10) days after notified by Spectrum. EPRO’s approval may not be withheld unreasonably. 
 S.
“Territory” shall mean North America (namely, the United States and its territories and protectorates, Canada and Mexico). 
 T. “Third Party” shall mean any person or entity other than a Party or an Affiliate or Sublicensee. 
 U. “University Agreement” shall mean that certain license agreement, attached hereto as Exhibit B, by and between Targent and the University of Strathclyde (the “University”), dated
March 15, 2006, and subsequently assigned to Spectrum in conjunction with Spectrum’s acquisition from Targent of all of the rights and assets regarding the Licensed Technology. 

V. “Valid Claim” shall mean a claim in any unexpired, issued patent (and as applicable, patents and patent applications
covering Improvements) within the Licensed Patents which has not been held invalid and/or unenforceable in a decision by a court or other body of competent jurisdiction from which there is no appeal or, if appealable, from which no appeal has been
taken. 
 ARTICLE II - GRANT OF LICENSE 
 A. Grant of License. 
 As of the Effective Date of this Agreement, EPRO
hereby grants to Spectrum during the term of this Agreement and subject to the terms hereof, 
  

	 	(1)	an exclusive license (even as to EPRO) to use the Documents and a non-exclusive license under the Licensed Technology to develop, make, have made, use, sell and have
sold a Licensed Product in the Field of Use in the Territory; 

  
 4 

	 	(2)	the right to grant to Sublicensees, a sublicense under the Documents and the Licensed Technology licensed by subparagraph (1) of this Article II (A) of no
greater scope than the license granted hereunder to Spectrum, provided that party shall have agreed with Spectrum to be bound by the terms of this Agreement insofar as they relate to the operations of that party. 

 

	 	(3)	EPRO agrees not to grant any further licenses under the Documents and the Licensed Technology to Third Parties in the Field of Use in the Territory.

 B. Improvements that are made by an employee, agent or consultant of Spectrum, solely or jointly with a Third
Party, shall be owned by Spectrum. Improvements that are made by an employee, agent or consultant of EPRO, solely or jointly with a Third Party, shall be owned by EPRO. Improvements that are made jointly by employees, agents or consultants of
Spectrum and EPRO and its employees, agents or consultants (“Joint Inventions”) shall be jointly owned by Spectrum and EPRO and treated as joint inventions under U.S. laws applicable to joint inventions. EPRO shall, and hereby does, grant
Spectrum the exclusive and unrestricted right in the Field of Use in the Territory to make, have made, use, sell, have sold, import, export and license EPRO’s interest in all Joint Inventions. EPRO hereby grants to Spectrum the exclusive
and unrestricted right in the Field of Use to make, have made, use, sell, have sold, import, export and license all Improvements made solely by EPRO, its employees or consultants in accordance with the provisions of the present Agreement. Spectrum
hereby grants to EPRO the exclusive and unrestricted right in the Field of Use outside the Territory and/or outside the Field of Use in or outside the Territory to make, have made, use, sell, have sold, import, export and license Spectrum’s
improvements and interest in all Joint Inventions, subject to the provisions of Article II (D) of this Agreement under commercially reasonable conditions to be negotiated in good faith between the parties which conditions shall be similar to
those contained in this Agreement. In addition, the Parties agree to negotiate in good faith the terms of a license agreement governing EPRO’s use of such Improvements and Joint Inventions. EPRO shall, and hereby does, after Spectrum’s
royalty obligations under Article V (A)(2) have expired or been terminated by Spectrum due to a breach of this Agreement by EPRO or due to the insolvency of EPRO pursuant to Article IX, grant Spectrum a perpetual, royalty-free license to use all
Improvements owned by EPRO and all information, know-how and other data pertaining to all Improvements and the Joint Inventions. Spectrum shall own any trademarks associated with the Licensed Products that it creates. 

C. To the extent that EPRO has granted or, during the term of this Agreement until acceptance of Phase IV data by regulatory agencies,
grants, a license under the Licensed Technology to make, have made, use and sell the Licensed Product in the Field of Use outside the Territory to any Third Party, EPRO shall require such Third Party licensee(s) to promptly forward any and all
safety data obtained by any such Third Party pursuant to such license to Spectrum for it to use in its Phase IV clinical trials. Spectrum will treat such data as confidential in accordance with Article III (B) herein and, upon written request
by EPRO, will return such data to EPRO upon acceptance of Phase IV data by regulatory agencies. 

  
 5 

 D. EPRO shall have the right to license the Licensed Technology to a Third Party or Third
Parties for use outside the Field of Use in the Territory or develop the Licensed Technology itself to market a Product for use outside the Field of Use in the Territory; provided, however, that EPRO shall first give an opportunity to Spectrum for
an exclusive license under the Licensed Technology to manufacture, have manufactured, use and sell Licensed Product outside the Field of Use in the Territory using Levofolinic Acid as either the free acid or in any salt form through a right of final
negotiation to be completed not later than three (3) months after the date of receipt by Spectrum of written notice from EPRO of such an opportunity. Both Parties agree to negotiate in good faith to reach such an agreement. 

E. Manufacturing Information. 
 EPRO shall disclose all information it owns, or has the right to disclose to Spectrum to enable Spectrum to manufacture and use Licensed Products. This information shall include complete details of the
manufacturing process to produce Licensed Product in finished form. 
 F. Non-Assert Provision. 

EPRO will not, 
  

	 	(1)	assert any of the Licensed Patents to prevent the use or sale of the Licensed Product in the Territory by any Third Party obtaining Licensed Product from Spectrum (for
purposes of this Article II (F), the term “Spectrum” shall include Third Parties used by Spectrum to market the Licensed Product), its Affiliate or by a Sublicensee; nor 

 

	 	(2)	assert any other patent or patent application now or hereafter controlled (in the sense of having the right to grant licenses or sublicenses) by EPRO to the Licensed
Technology to prevent any party obtaining Licensed Product from Spectrum, its Affiliate or a Sublicensee from using or selling any Licensed Product. 

 G. EPRO shall during the initial Regulatory Exclusivity Period not introduce, market or sell in the Territory any product which would be a substitute for Leucovorin and that directly competes with a
Licensed Product. Notwithstanding the foregoing, EPRO shall be able to manufacture and/or supply a product that competes with a Licensed Product to a Third Party. For the avoidance of doubt, it is acknowledged, that this paragraph shall not bind any
other company of the Merck Group, to which EPRO belongs. 
 H. EPRO shall not take any action against the University in
connection with the patents listed in Schedule A of the University Agreement the result of which causes Spectrum to lose its exclusive license to such patents. 

  
 6 

 ARTICLE III - TECHNICAL INFORMATION AND CONFIDENTIALITY 

A. Information to be Transmitted. 
 EPRO shall, upon the Effective Date of this Agreement, deliver to Spectrum any Licensed Know-How necessary for Spectrum to fulfill its obligations pursuant to Article VI(A). 

B. Confidentiality. 
 The terms of that certain Mutual Confidentiality Agreement by and between the Parties, dated November 1, 2005, (to the extent such Mutual Confidentiality Agreement is not inconsistent with this
Agreement) shall be in addition to the provisions of this subsection. The Parties contemplate that during the course of their relationship it may be necessary to provide the other with Confidential Information to facilitate the performance of their
obligations pursuant to this Agreement. Confidential Information received from the disclosing Party which is in writing and identified as confidential or, if disclosed orally, is summarized in writing and designated confidential, shall be maintained
in confidence and that reasonable and prudent practices shall be followed to maintain the information in confidence including, where necessary, obtaining written confidentiality agreements from employees not already bound by such agreements who have
access to the Confidential Information. Confidential Information shall be used by a Party only for the purpose of and in connection with its performance under this Agreement. The obligation to maintain information in confidence shall survive this
Agreement or termination thereof for any reason for a period of seven (7) years thereafter. However, the obligations of nondisclosure and limited use shall not apply to information which can be shown by written documentation: 

 

	 	i.	to have been publicly known prior to disclosure by the disclosing Party to the receiving Party; or 

 

	 	ii.	to have been known or available to the receiving Party prior to disclosure by the disclosing Party as shown by its prior written records; or 

 

	 	iii.	to have become publicly known, without fault on part of the receiving Party, subsequent to disclosure by the disclosing Party; or 

 

	 	iv.	to have been received by the receiving Party from a Third Party legally having possession of the information without obligations of confidentiality; or

  
 7 

	 	v.	to have been independently developed by or for the receiving Party without reliance on information received from the disclosing Party; or 

 

	 	vi.	to be required to be disclosed pursuant to order of any court or governmental agency having jurisdiction thereof after notice to the disclosing Party sufficient to
afford it an opportunity to intervene in the proceeding where disclosure is required. 

 Confidential Information
shall not be deemed to be within the foregoing exceptions merely because it is embraced within broader or general disclosures known to the public or the recipient Party, and any combination of features shall not be deemed to be within the foregoing
exceptions merely because individual features are known to the public or to the recipient unless the whole combination of features and its principle of operation are known. 
 ARTICLE IV - REPRESENTATIONS, WARRANTIES AND INDEMNIFICATION 
 A. Mutual
Representations. Each of the Parties represents and warrants that: 
  

	 	(a)	It is a corporation or entity duly organized and validly existing under the laws of the state or other jurisdiction of its incorporation or formation.

  

	 	(b)	The execution, delivery and performance of this Agreement by such Party have been duly authorized by all requisite corporate action. 

 

	 	(c)	It has the power and authority to execute and deliver this Agreement and perform its obligations hereunder and thereunder. 

 

	 	(d)	The execution, delivery and performance by such Party of this Agreement does not and will not conflict with or result in breach of the terms and provisions of any other
agreement or constitute a default under (i) a loan agreement, guaranty, financing agreement, affecting a product or other agreement or instrument binding or affecting it or its property; (ii) the provisions of its charter or operative
documents or bylaws; or (iii) any order, writ, injunction or decree of any court or governmental authority entered against it or by which any of its property is bound. 

  
 8 

	 	(e)	The execution, delivery and performance of this Agreement by such Party does not require the consent, approval or authorization of, or notice, declaration, filing or
registration with, any governmental or regulatory authority in the Territory and the execution, delivery and performance of this Agreement does not violate any law, rule or regulation applicable to such Party. Notwithstanding the foregoing, Spectrum
may be required to file notices with the necessary regulatory authorities to notify them of Spectrum’s ownership of the regulatory filings described in Article VI (A) (3). 

 

	 	(f)	This Agreement has been duly authorized, executed and delivered and constitutes such Party’s legal, valid, and binding obligation enforceable against it in
accordance with their terms subject, as to enforcement, to bankruptcy, insolvency, reorganization and other laws of general applicability relating to or affecting creditors’ rights and to the availability of particular remedies under general
equity principles. 

  

	 	(g)	It shall comply with all applicable laws and regulations relating to its activities under this Agreement. 

 

	 	(h)	It is not debarred and has not and will not use in any capacity the services of any person debarred under subsections 306 (a) and (b), of the Generic Drug
Enforcement Act of 1992. If at any time during the term of this Agreement this warranty is no longer accurate, the affected Party shall immediately notify the other and the Parties shall negotiate to resolve issues that may affect Spectrum’s
ability to manufacture, have manufactured, use or sell Licensed Products. 

 B. EPRO Representations.

 EPRO represents and warrants that, as of the Effective Date: (a) to the best of its knowledge, it is the owner of all
right, title and interest in and to the Licensed Technology; (b) it has not received any written notice and, to the best of its knowledge, operating under the Licensed Technology does not infringe the proprietary rights of any Third Party;
(c) there are no claims, judgments or settlements against or owed by EPRO, or pending or threatened claims, or litigation, relating to the Licensed Technology; (d) to the best of its knowledge, Exhibit A is a complete and accurate listing
of all patents and patent applications subject to grant hereunder; (e) EPRO has not granted any right, license or interest in or to the Licensed Technology, or any portion thereof, inconsistent with the rights granted to Spectrum herein;
(f) to the best of its knowledge, no Third Party has any right or authority to prohibit Spectrum from using the Licensed Technology in the Territory in any way; and (g) the exclusive rights of Wyeth to the Licensed Technology have been
converted into non-exclusive rights and Wyeth has completely transferred to EPRO all of its rights in the regulatory filings made in the Territory related to the Licensed Technology, including, but not limited to, IND #32,487, NDA #’s 20-140
and 20-141 and the related orphan drug designations. 

  
 9 

 In the event an injunction is issued against Spectrum because of infringement of Third Party
intellectual property rights, the parties will share liability for Spectrum’s expenses. If the injunction is not dissolved within three (3) months after issuance, then Spectrum shall be solely responsible for its legal expenses in
attempting to dissolve such injunction thereafter. 
 C. Indemnification. 

EPRO shall indemnify and hold Spectrum harmless from and against any liability, loss, cost, expense (including reasonable attorneys’
fees), damage, or penalty of any kind, on account of or resulting from (i) any breach by EPRO of its representations and warranties contained in this Article IV, (ii) any breach by EPRO of any covenant contained in this Agreement, and
(iii) any claim or action for infringement of any Third Party intellectual property rights as a result of Spectrum’s operations under the Licensed Technology in the Territory in accordance with this Agreement claimed or issued before the
Effective Date, except for claims by the University related to the patents listed in Schedule A of the University Agreement or claims by Wyeth related to the Licensed Technology, both of which shall be covered by this Article IV (C). EPRO’s
liability under this paragraph IV(C)(iii) shall be limited to the amount of damages/royalties imposed on Spectrum by judgment or settlement upon the finding of infringement and shall be further limited to the amount of Fees (as hereinafter defined)
paid by Spectrum to EPRO. EPRO shall have the right, at any time, to join negotiations with a Third Party whose intellectual property rights are alleged to be infringed or to take over negotiations with that Third Party if the scope of the alleged
infringement is outside the scope of Spectrum’s operations under this Agreement. Any settlement of such alleged infringement shall be agreed to by both parties, which EPRO’s consent shall not be unreasonably withheld. 

Spectrum shall indemnify EPRO and hold EPRO harmless from and against any liability, loss, cost, expense (including reasonable
attorneys’ fees), damage, or penalty of any kind, on account of or resulting from (i) any breach by Spectrum of its representations and warranties contained in this Article IV and (ii) any breach by Spectrum of any covenant contained
in this Agreement. 
 ARTICLE V - PAYMENTS AND REPORTS 
 A. Fees. In consideration for the license granted hereunder, Spectrum shall pay EPRO the following fees in U.S. Dollars (“Fees”): 

(1) Up-Front and Progress Payments (all payments are one-time payments): 

(a) Within thirty (30) days after NDA approval by the FDA for an injectable form of a the Licensed Product, a progress payment of
one hundred thousand dollars ($100,000); 

  
 10 

 (b) Within thirty (30) days after NDA approval by the FDA of an oral form of a
Licensed Product, a progress payment of two hundred thousand ($200,000). 
 (2) Royalties: 

Spectrum shall pay EPRO, beginning with the first commercial sale of the Licensed Product in a particular country and
expiring on the later of (a) the expiration of the last of the patents licensed hereunder issued in that country that includes a Valid Claim that would, in the absence of the license granted hereunder, be infringed by the sale of a Licensed
Product, or (b) the expiration of all Regulatory Exclusivity Periods with respect to the Licensed Product in such country, royalties based on quantities of the Licensed Product sold by Spectrum, its Affiliates; and/or its Sublicensees in
accordance with the following formula: 
 (a) Four and one-half percent (4 1/2%) of Net Sales of the Licensed Product for sales annually of up to and including twenty-five million dollars ($25,000,000); 

(b) Five percent (5 %) of Net Sales of the Licensed Product for sales annually between twenty-five million dollars ($25,000,000) and up
to and including fifty million dollars ($50,000,000); 
 (c) Six percent (6%) of Net Sales of the Licensed Product for
sales annually between fifty million dollars ($50,000,000) and up to and including one hundred million dollars ($100,000,000); 

(d) Seven percent (7%) of Net Sales of the Licensed Product for sales annually of over one hundred million dollars ($100,000,000);

 After Spectrum is no longer required to pay any royalty described under subparagraphs (a) through (d) above in a
particular country in the Territory, then Spectrum shall pay EPRO a royalty of two (2%) percent of Net Sales of the Licensed Product in such country until a generic version of such Licensed Product is sold within such country. 

(3) EPRO shall be responsible for any fees owed by Spectrum to the University pursuant to Articles III (A) (1) &
(2) of the University Agreement. Therefore, Spectrum shall be able to deduct from any payments owed to EPRO under Articles V (A) (1) & (2) of this Agreement, any amounts owed to the University pursuant to Articles III
(A) (1) & (2) of the University Agreement. Information regarding such deductions shall be included in the reports provided in Article (V) (B) below. In addition, in the situation where Spectrum owes an amount to the
University pursuant to Articles III (A) (1) & (2) of the University Agreement, but Spectrum is unable to deduct it from a payment owed to EPRO, Spectrum shall provide EPRO with a report of such amount paid to the University and
EPRO shall pay Spectrum such amount within thirty (30) days. EPRO shall not be responsible for any fees owed by Spectrum to the University pursuant to Article III (A) (3) of the University Agreement. 

  
 11 

 B. Reports and Remittances. Until such time as Spectrum, its Affiliates, its
Sublicensees have sold all quantities of the Licensed Product subject to fee hereunder, Spectrum shall report in writing to EPRO within sixty (60) days after the end of each calendar quarter the quantities of each Licensed Product subject to
fee hereunder that were sold by Spectrum, its Affiliates, its Sublicensees during said quarter and the calculation of the fees thereon. With said report Spectrum shall pay to EPRO the total amount of the said fees. If no Licensed Product subject to
fee hereunder has been sold by Spectrum, its Affiliates, any Sublicensees during any such period, Spectrum shall so report in writing to EPRO within sixty (60) days after the end of such period. Reports, notices and other communications to EPRO
hereunder shall be sent to: 
  

									
	 	 	 	 	Merck Eprova AG	 	 
		 		 	Im Laternenacker 5	 	
		 		 	8200 Schaffhausen	 	
		 		 	Switzerland	 	
		 		 	Attention:	 	Martin Ulmann	 	
		 		 		 	General Manager	 	
		 		 	Fax:	 	++41(0)52 630 72 55	 	

 Each payment to EPRO hereunder shall be sent to EPRO under separate cover along with a copy of the relevant report to:

  

									
	 	 	 	 	Merck Eprova AG	  	 
		 		 	Im Laternenacker 5	  	
		 		 	8200 Schaffhausen	  	
		 		 	Switzerland	  	
		 		 	Attention:	  	Martin Ulmann	  	
		 		 		  	General Manager	  	

 Notices to Spectrum shall be sent to the address set forth above unless a different address is designated
in writing by Spectrum. 
 C. Taxes. If laws, rules or regulations require withholding of income taxes or other rates
imposed upon payments set forth in this Article V, Spectrum may make such withholding payments as required and subtract such withholding payments from the payments set forth in this Article V. Spectrum shall submit appropriate proof of payment of
the withholding rates to EPRO within a reasonable period of time. Spectrum shall use efforts consistent with its usual business practices to ensure that any withholding taxes imposed are reduced as far as possible under the provisions of the current
or any future double taxation treaties or agreements between foreign countries, and the Parties shall cooperate with each other with respect thereto, with the appropriate Party under the circumstances providing the documentation required under such
treaty or agreement to claim benefits thereunder. 

  
 12 

 D. Records. Spectrum shall keep full, complete and proper records and accounts of all
sales of Licensed Products by Spectrum, its Affiliates, and to the extent it acquires rights to do so, its Sublicensees, in accordance with GAAP, in sufficient detail and in the currencies in which the sale was made to enable the royalties payable
on each Licensed Product to be determined. All such records, statements, reports and accounts referred to in this Article shall be retained for a period of three (3) years after the end of the period to which they apply. 

E. Audit. If EPRO disagrees with a report provided by Spectrum, pursuant to Article V (B), EPRO, at its own expense, shall have
the right, upon reasonable prior notice during regular business hours, to meet with Spectrum’s independent auditor to inspect and discuss the books and accounts of Spectrum or its Affiliates, related to the payment and calculation of royalties
arising under this Agreement. After this inspection, if EPRO still disagrees with the report provided by Spectrum, with reasonable justification for such disagreement, EPRO, at its own expense, shall have the right, upon reasonable prior notice
during regular business hours, to appoint independent auditors reasonably acceptable to Spectrum and have them during normal business hours, inspect the books and accounts of Spectrum or its Affiliates, related to the payment and calculation of
royalties arising under this Agreement. Spectrum shall cooperate and cause Spectrum’s Affiliates, to cooperate with such auditors. The auditors performing the audit shall disclose to EPRO only information relating to the accuracy of records
kept and the payments made, and shall be under a duty to keep confidential any other information obtained from such records. If any such audit establishes that Spectrum has underpaid or overpaid the amount due, Spectrum shall promptly pay any
remaining amounts due as established by such audit or EPRO shall promptly refund any over payment. If the underpayment is by seven percent (7%) or more during any calendar year, Spectrum shall reimburse EPRO for the reasonable expenses of such
audit. 
 ARTICLE VI - SPECTRUM DELIVERABLES 
 A. Government Approvals. 
  

	 	(1)	In consideration for the licenses granted hereunder, Spectrum, at its cost and expense, shall use commercially reasonable efforts to complete, file and actively pursue
an NDA for one or more Licensed Products in the Territory. Spectrum shall use its commercially reasonable efforts to file a reasonable response to the most recent deficiency letter from the FDA for the NDA for the use of a Licensed Product for
injection for methotrexate rescue within eighteen months (18) after signing of this Agreement. 

  
 13 

	 	(2)	The Parties shall form a committee with two (2) representatives each from both Parties in order to provide a forum whereby Spectrum can regularly update EPRO on
the progress in developing the Licensed Product(s). 

  

	 	(3)	Any and all registrations and/or regulatory filings with the FDA or other appropriate regulatory agency in the Territory for the Licensed Products in the Field of Use
will be filed in the name of Spectrum as the sponsor of the NDA or other appropriate registration in the Territory and shall be owned by Spectrum. In addition, any registrations and/or regulatory filings that have been previously filed shall be
transferred and placed in the name of Spectrum and shall be owned by Spectrum. 

  

	 	(4)	It is the parties’ expectation that EPRO shall be permitted to make reference to and utilize the technical, manufacturing, safety and efficacy clinical data
included in Spectrum’s application for the development and use of, and regulatory approval for, the manufacture, use and sale of Licensed Product except where such use of data would derogate from Spectrum’s exclusive rights in the Field of
Use in the Territory. EPRO shall also be permitted such use of data outside the Field of Use in the Territory under the conditions described in the preceding sentence with the proviso that EPRO obtains Spectrum’s prior written consent
and subject to Article II (D) of this Agreement. 

 B. Product Marketing. Spectrum will, at its
expense and upon approval of the NDA for the Licensed Product, begin marketing efforts in the Territory to promote and sell the Licensed Product, and will provide EPRO marketing plans to that end on an annual basis. 

C. Spectrum Efforts. Spectrum, its Affiliates, and/or its Sublicensees shall perform their obligations under the Agreement by
expending their commercially reasonable efforts by exercising the same level of effort to promote, advertise and market Licensed Product as they expend for their other respective products with similar sales potential. 

D. Non-Competition. Spectrum, and its Sublicensees will not, for a period of three (3) years from the first commercial sale
of the Licensed Product, as long as the Agreement is in effect, introduce, market or sell in the Territory and in the same Field of Use any new product which is an isomeric form of leucovorin. 

  
 14 

 ARTICLE VII - INTELLECTUAL PROPERTY 

A. Trademarks. EPRO shall have the right, in its sole discretion and at its own expense, to select and register such trademarks as
it wishes to employ in connection with the sale of the Licensed Product outside the Field of Use throughout the Territory and EPRO shall have legal and equitable ownership of the entire right, title and interest in and to the trademarks and
registrations EPRO elects to use. In the event that any trademarks applications are filed or registrations issued, EPRO hereby grants to Spectrum, for the term of this Agreement, a non-exclusive license to use such trademarks in connection with the
promotion and sale of the Licensed Product in the Field of Use. 
 B. Prosecution of Patents. EPRO shall be solely
responsible for preparing, prosecuting and maintaining the Licensed Patents, including payment of all necessary filing and maintenance fees. 
 (a) Each Party shall cooperate with the other Party to execute all required papers and instruments and to make all required oaths and declarations as may be necessary in the preparation and prosecution of
all such patents and other applications and protections referred to in this Article. 
 (b) In the event that EPRO wishes to
abandon any patent within the Licensed Patents, EPRO will offer to assign to Spectrum, free of charge, any such patent prior to effectuating the abandonment. Spectrum shall bear the costs connected with any assignment, and recordation thereof,
hereunder. 
 ARTICLE VIII - ABATEMENT OF INFRINGEMENT 
 A. If at any time any Third Party shall infringe to a commercially substantial extent any patent licensed hereunder then Spectrum shall promptly inform EPRO of such infringement and EPRO shall, subject to
Paragraph (C) of this Article, either (a) obtain a discontinuance of said infringing operations or (b) bring suit at its own expense against such infringer, bringing said suit in the name of EPRO and, if so required by the law of the
forum, bringing suit in the name of Spectrum or joining Spectrum as a party plaintiff with EPRO. In such an event and until EPRO effectuates discontinuance of infringement, Spectrum’s applicable royalty rates shall be reduced to one third
(1/3) of the rates indicated in Article V. Upon discontinuance of such infringement, Spectrum shall resume paying royalties at the rates indicated in Article V(A)(2). EPRO shall be entitled to receive and retain all recoveries from such
infringement. 
 B. Spectrum shall have the right, in any suit brought by EPRO pursuant to paragraph (A) of this Article,
to be represented at its own expense by counsel of its own selection to the extent of having access to full information and opportunity to be heard in the councils of EPRO. 

  
 15 

 C. In the event that EPRO neither brings suit against a Third Party as provided in paragraph
(A) of this Article nor obtains a discontinuance of such infringing operations within six (6) months of the date of receipt of such notice, then Spectrum may at its election bring suit in its own name against such infringer. Should
Spectrum bring suit in its own name, EPRO shall execute such legal papers necessary for the prosecution of such suit as may be requested by Spectrum, and Spectrum shall be liable for all costs and expenses of such litigation and shall be entitled to
receive and retain all recoveries therefrom. During the pendency of such suit by Spectrum, and in the event of an adverse outcome of such suit, Spectrum’s royalty obligations shall be reduced as indicated in paragraph (A) of this Article
or eliminated in the latter case. 
 D. If a Third Party makes or threatens against Spectrum, its Affiliates or its Sublicensees
any claim of infringement of a patent right based upon the use of, or arising as a result of the exercise of the rights and licenses granted hereunder to the Licensed Technology (each an “Alleged Infringement”), Spectrum shall have
the right to respond to and defend any and all such Alleged Infringements at its own cost and expense, and in its sole discretion. EPRO agrees to provide any necessary assistance that Spectrum may reasonably require in any such defense action for
which Spectrum shall pay to EPRO a reasonable hourly rate of compensation. EPRO shall have the right, at its own expense, to retain counsel of its choice to represent it in any such defense action. Spectrum shall notify EPRO in writing and provide a
copy of (i) any claim of Alleged Infringement filed with a court or governmental authority or (ii) any written notice of an Alleged Infringement from an attorney or law firm. Within a reasonable period of time in advance of any responsive
deadline required by law or otherwise set forth in the claim or notice of Alleged Infringement, Spectrum shall notify EPRO in writing as to whether or not Spectrum intends to respond to such Alleged Infringement. In the event that Spectrum does not
intend to respond to any such claim or notice or, if Spectrum, in its sole discretion, asks EPRO to respond to any such claim or notice, EPRO shall have the right, in its sole discretion, to respond to and litigate or settle such Alleged
Infringement, in which case EPRO shall pay any and all future costs and expenses incurred by Spectrum in such action, and shall indemnify, defend and hold Spectrum, its Affiliates and its Sublicensees harmless from any future costs, expenses or
liability respecting all such actions undertaken by EPRO. This Article VIII (D) shall not amend or reduce EPRO’s indemnification obligations under Article IV (C). 
 ARTICLE IX - TERMINATION 
 A. Termination. Unless terminated early in
accordance with the provisions of this Agreement, the term of this Agreement shall endure on a Licensed Product-by-Licensed Product and country-by-country basis until the expiration of the obligation to pay royalties under Article V
(A) (2) above applicable to such Licensed Product in such country. This Agreement shall expire in its entirety after the date that Spectrum no longer owes any royalties to EPRO under Article V (A) (2). 

B. Early Termination by Spectrum. Spectrum shall have the unilateral right to terminate this Agreement, in its entirety or on a
Licensed Product-by-Licensed Product or country-by-country basis, at any time for any reason upon prior written notice to EPRO given at least nine (9) months prior to the desired termination. 

  
 16 

 C. Early Termination by EPRO. EPRO shall have the unilateral right to terminate this
Agreement, in its entirety upon prior written notice to Spectrum if Spectrum has failed to comply with the obligations laid down in Article VI (A) (1), provided that the non-performance is not due to (i) scientific, medical or technical
issues arising in the development of the Licensed Product, including, without limitation, manufacturing issues, adverse clinical trial results or patient reactions, or a request by the FDA to conduct additional clinical trials with respect to the
Licensed Product, (ii) circumstances beyond Spectrum’s control, (iii) an event of Force Majeure (as defined in Article XII), and/or (iv) the fault of EPRO. 
 D. Termination upon Breach. In the event that any stipulation or provision of this Agreement is materially breached by a Party, the other Party may terminate this Agreement upon ninety
(90) days’ written notice to the breaching party. However, if such breach is corrected within the ninety (90) day period, and there are no unreimbursed damages resulting from the breach, this Agreement shall continue in force. A
material breach by Spectrum of its obligations under Article VI (A) (1) shall be governed by Article IX (C). 
 E.
Insolvency. Should a Party (1) become insolvent or unable to pay its debts as they mature, (2) make an assignment for the benefit of creditors, (3) permit or procure the appointment of a receiver for its assets, or
(4) become the subject of any bankruptcy, insolvency or similar proceeding, then the other Party may at any time thereafter on written notice to the insolvent Party, effective forthwith, cancel this Agreement. 

F. Effect of Termination. 
  

	 	(1)	Upon termination of this Agreement pursuant to Article IX (A), the licenses granted hereunder shall be considered fully-paid and Spectrum and its Sublicensees shall be
free to continue to use the Licensed Technology and Documents to make, use and sell the Licensed Products without further financial obligations to EPRO hereunder. Other than rights intended to survive expiration, or royalties or fees that accrued
during the term of the Agreement in accordance with Article V (A) (2), neither Party shall have any further rights or obligations upon the expiration of this Agreement. 

  
 17 

	 	(2)	Upon termination of this Agreement by EPRO pursuant to Articles IX (C), (D) or (E), or by Spectrum pursuant to Article IX (B), occurring prior to the regularly
scheduled expiration date of this Agreement, (i) all rights and licenses granted by EPRO to Spectrum including any rights to the Licensed Product shall terminate and revert to EPRO and (ii) Spectrum shall return to EPRO or destroy at
EPRO’ option all copies of the Licensed Know-How. The foregoing provisions shall also apply to the partial termination of this Agreement by Spectrum in accordance with Article IX (B), provided, however, that in such event: (1) only
those rights that solely pertain to the Licensed Product and/or country being terminated would revert back to EPRO; (2) only copies of the Licensed Know-How that solely pertain to the Licensed Product and/or country being terminated would be
returned or destroyed by Spectrum. Notwithstanding the foregoing, Spectrum shall retain its right, title and interest under Article II (B) in any Improvements made solely by Spectrum and in any Joint Inventions. 

 

	 	(3)	Upon any termination of this Agreement by Spectrum under Articles IX (D) or (E) occurring prior to the regularly scheduled expiration date of this Agreement,
the license rights granted by EPRO to Spectrum contained in this Agreement shall continue in full force and effect, however, Spectrum’s obligations under this Agreement to pay royalties shall terminate. 

G. Obligations of the Parties. The obligations of the Parties under Articles II (F), III (B), IV(C), V (A) (3), IX
(F) & (G), and Articles VIII, XI, XIII and XV and any other provisions which are expressly indicated to survive expiration or termination, shall remain in effect upon any termination or expiration of this Agreement as shall Spectrum’s
obligations under Articles V (A) (2) (a) - (d) for Licensed Products sold prior to such termination or expiration. 
 ARTICLE X -
ASSIGNABILITY 
 Except for sublicensing rights as set forth in Article II (A) (2), this Agreement shall not be
assignable in whole or part to any Third Party without the prior written consent of the other Party (such consent not to be unreasonably withheld), except, to a successor in interest pursuant to a merger, acquisition or sale of all or substantially
all of the assignor’s assets to which this Agreement relates. Any attempted assignment in violation of this provision shall be null and void. 
 ARTICLE XI - APPLICABLE LAW 
 This Agreement is acknowledged to have been
made in and shall be construed in accordance with the laws of Switzerland without regard to the principles thereof relating to the conflict of laws; provided that all questions concerning the construction or effect of patent applications and patents
shall be decided in accordance with the laws of the country in which the particular patent application or patent concerned has been filed or granted, as the case may be. 

  
 18 

 ARTICLE XII - FORCE MAJEURE 
 Neither Party shall be responsible to the other for delay or failure in performance of any of the obligations imposed by this Agreement, provided such delay or failure shall be occasioned by a cause
beyond the control of and without the fault or negligence of such Party, including fire, flood, explosion, lightning, windstorm, earthquake, subsidence of soil, failure of machinery or equipment or supply of materials, discontinuity in the supply of
power, court order or governmental interference, civil commotion, riot, war, terrorism or terroristic threats, strikes, labor disturbances, transportation difficulties or labor shortage. Notwithstanding the aforesaid, if either Party fails to a
substantial extent for at least six (6) months to fulfill any of its obligations under this Agreement, the other Party may terminate the Agreement. 
 ARTICLE XIII - DISPUTE RESOLUTION 
 In the event that a dispute arises
between the Parties, the following procedures shall be followed: 
 A. Negotiations. In the event that any dispute may
arise, the Parties shall first seek to resolve any disputes by negotiation among senior executives who have authority to settle the controversy, as follows: 
  

	 	(a)	Notification. When a Party believes there is a dispute relating to the Agreement, the Party will give the other Party written notice of the dispute.

  

	 	(b)	Meeting Among Senior Executives. The senior executives shall meet at a mutually acceptable time and place within thirty (30) days after the date of the
notice to exchange relevant information and to attempt to resolve the dispute. 

  

	 	(c)	Confidentiality. All negotiations are confidential, shall be treated as compromise and settlement negotiations, and neither party shall use information obtained
during such negotiations in any subsequent dispute resolution proceeding. 

 B. Mediation. If the dispute
has not been resolved within thirty (30) days after the date of the notice of a dispute, or if the Party receiving such notice fails or refuses to meet within such time period, either Party may initiate mediation of the dispute by sending the
other Party a written request that the dispute be mediated. The Party receiving such a written request will promptly respond to the requesting Party so that both Parties can jointly select a neutral and impartial mediator and schedule the mediation
session. The Parties shall mediate the dispute before a neutral, third-party mediator within thirty (30) days after the date of the written request for mediation. 

  
 19 

 C. Arbitration. Any controversy or claim arising out of or relating to this Agreement
or the breach thereof, and not settled as described in Article XIII (A) or (B), shall be settled by arbitration in accordance with the Licensing Agreement Arbitration Rules of the International Chamber of Commerce, utilizing the laws of
Switzerland, without giving effect to its conflicts of laws rules, and judgment upon the award rendered by the Arbitrator(s) may be entered in any Court having jurisdiction thereof. The situs of arbitration shall be Schaffhausen, Switzerland if
initiated by Spectrum and Irvine, California if initiated by EPRO. 
 ARTICLE XIV - ADJUDICATION OF LICENSED PATENTS 

Should any Licensed Patents be declared invalid or not infringed or limited in scope by a final decision (from which no appeal is or can
be taken) of a court or other tribunal of competent jurisdiction in the country in which said patent was granted, then the construction placed upon the patent by said court or other tribunal shall be followed by the Parties from and after the date
of entry of the decree of said court or tribunal and fees shall thereafter be payable to EPRO only in accordance with such construction. 

ARTICLE XV - MISCELLANEOUS PROVISIONS 
 A. The rights and remedies provided in this Agreement are cumulative and not exclusive of any rights or remedies provided by law or in equity. 

B. Except as required by law or the rules of the principal stock exchange on which the Party’s stock is traded, no Party shall
originate any public statement, news release or other written public announcement, whether in the public press, stockholders’ reports, or otherwise, relating to this Agreement or to any sublicense hereunder, or to the performance hereunder or
any such agreements, or use a Party’s name for any purpose, including, without limitation, in connection with the advertising or sale of Licensed Products, without the prior written approval of the other Party, such consent not to be
unreasonably withheld. The Parties each agree to respond to each such request within five (5) business days of receipt of a request (unless a shorter period of time is necessary to comply with law). Notwithstanding anything to the contrary in
this Agreement, each party shall be permitted to publicly disclose (i) the existence of this Agreement, (ii) that EPRO and Spectrum are the parties to this Agreement, and (iii) the Licensed Technology covered by this Agreement. In the
case of unintentional public disclosure concerning this Agreement, any Licensed Product or any other subject matter hereof, the disclosing Party shall promptly inform the other Party of such disclosure and the other Party shall be entitled to make a
public announcement regarding the subject matter of the disclosure. The other Party shall notify the disclosing Party of their intention to make such an announcement. Following a Party’s consent to or approval of the public announcement of any
information pursuant to this Article, both Parties shall be entitled to make subsequent public announcements of such information without renewed compliance with this Article, unless the scope and/or duration of such consent or approval is expressly
limited. 

  
 20 

 C. This Agreement embodies the entire understanding of the Parties and shall supersede all
previous communications, representations, undertakings or agreements, between them, either verbal or written, relating to the subject matter hereof. 
 D. This Agreement shall be binding upon and enure to the benefit of the successors, permitted assignees and personal representatives of the Parties. 

E. In the event that any one or more of the provisions contained in this Agreement shall for any reason be held to be invalid, illegal or
unenforceable in any respect, such invalidity, illegality or unenforceability shall not affect any other provision hereof, and this Agreement shall be construed as if such invalid, illegal or unenforceable provisions or provisions had never been
contained herein. 
 [SIGNATURE PAGE FOLLOWS] 

  
 21 

 IN WITNESS WHEREOF, the Parties have executed this Agreement and have entered the
Effective Date on the first page hereof. 
  

									
	 	 	 	 	 	 	Merck Eprova AG
					
	By	 	     /s/ Thomas Suter
	 		 	By	 	     /s/ Martin Ulmann

	Title	 	Chief Financial Officer	 		 	Title	 	General Manager
	Date	 	June 1, 2006	 		 	Date	 	June 1, 2006
				
		 		 		 	Spectrum Pharmaceuticals, Inc.
					
		 		 		 	By	 	     /s/ Rajesh C. Shrotriya

		 		 		 		 	Rajesh C. Shrotriya, M.D.
		 		 		 	Title	 	Chairman, CEO & President
		 		 		 	Date	 	May 19, 2006

  
 22 

 EXHIBIT A 

 

					
		  		  	Normal
	Country	  	 Patent No.
 (Patent Application No.)
	  	Expiry Date
 (Filing Date)

 PROCESS FOR SEPARATION OF FOLINIC
ACID (INT. REF. 191) 
 The invention relates to a process for the preparation of (6S)-folinic
acid and its salts, comprising recrystallization of alkaline-earth salts of (6R,S)-folinic acid and, where necessary, liberation of the acid from the alkaline-earth folinates and/or, where necessary, conversion into the alkali salts by at least one
recrystallization in the presence of a base. and (6S)-folinic acid. 
 The invention additionally relates to the calcium-, magnesium-,
potassium- and sodium-(6S)-folinates 
  

									
	Country	 	Application No	 	Patent No	 	Date of Grant	 	Expiration Date
	Canada	 	566726	 	1 340 290	 	29/12/98	 	29/12/2015
	USA (PCT)	 	07/294631	 	Abandoned	 		 	
	USA (Continuation)	 	07/668681	 	5 134 235	 	28/07/92	 	28/07/2009
	USA (Cont./Div.)	 	07/896482	 	5 347 005	 	13/09/94	 	02/06/2012
	USA (Cont./Div.)	 	08/275474	 		 		 	
	USA (Cont./Div.)	 	08/459692	 	6 160 116	 	12/12/00	 	12/12/2017

 METHOD FOR THE PREPARATION OF
TETRAHYDROFOLATES (INT. REF. 194) 
 The invention relates to a new process for the preparation
of 5,10-methenyl-(6R)-, 5-formyl-(6S)- and/or 5-methyl-(6S)-tetrahydrofolic acid as well as of the salts thereof, characterized in that 5,10-methenyl-(6R,S)-tetrahydrofolic acid, the inner salt thereof and/or one of the salts thereof with strong
acids, is subjected to diastereomer separation by fractional crystallization and, if desired, the resulting 5,10-methenyl-(6R)-tetrahydrofolic acid is converted by treatment with a hydrolysing agent into 5-formyl-(6S)-tetrahydrofolic acid or by
treatment with a reducing agent into 5-methyl-(6S)-tetrahydrofolic acid, and/or a resulting free acid is converted into one of its salts by treatment with a base. 
  

									
	Country	 	Application No	 	Patent No	 	Date of Grant	 	Expiration Date
	Canada	 	604256	 	1 339 675	 	17/02/98	 	17/02/2015
	USA	 	373,007	 	5 006 655	 	09/04/91	 	29/06/2009

  
 23 

 PROCESS FOR THE SEPARATION OF
FOLINIC ACID (INT. REF. 195) 
 The invention relates to a method for the
resolution of (6R,S)-folinates into their diastereomers, which comprises adding a water-soluble alkali metal, ammonium or alkaline earth metal salt of an inorganic or organic acid to an aqueous solution of (6R,S)-folinic acid, removing by filtration
the salt which separates out, which consists predominately of the corresponding (6R)-folinate, and isolating the desired (6S)-folinate from the filtrate. 
 The resulting (6S)-folinates are valuable pharmaceuticals for the treatment of megaloblastic folic acid deficiency anemia, as antidote for enhancing the tolerability of folic acid antagonists,
specifically of aminopterin, methotrexate and 5-fluorouracil in cancer therapy (leucovorin rescue) and the treatment of autoimmune diseases such as psoriasis and rheumatoid arthritis as well as for enhancing the tolerability of certain
antiparasitics. 
  

									
	Country	 	Application No	 	Patent No	 	Date of Grant	 	Expiration Date
	Canada	 	2002430-5	 	2 002 430	 	04/03/97	 	07/11/2009
	USA	 	432,819	 	5 010 194	 	23/04/91	 	07/11/2009

  
 24 

 EXHIBIT B 
 LICENSE AGREEMENT 
 THIS AGREEMENT, effective this 15th day of March, 2006,
between the University of Strathclyde, a University incorporated by Royal Charter having its Principal Office at 16 Richmond Street, Glasgow, G1 1XQ, Scotland, United Kingdom (“Strathclyde”), and Targent Incorporated, a Delaware
corporation with its principal place of business at 181 Cherry Valley Road, Princeton, New Jersey 08540, United States (“Targent”). Strathclyde and Targent may hereinafter each be referred to as a Party or collectively as the Parties.

 W I T N E S S E T H, That: 

WHEREAS, Strathclyde has certain patent rights relating to the Licensed Products (as hereinafter defined); and 

WHEREAS, Targent desires to obtain a license under the Licensed Patents (as hereinafter defined) to undertake development of the Licensed
Products for commercialization in the Territory (as hereinafter defined) after receipt of approval from the Food and Drug Administration (“FDA”) for the Licensed Products. 

  
 25 

 NOW, THEREFORE, in consideration of the promises and the mutual covenants herein contained,
and other good and valuable consideration, the Parties agree as follows: 
 ARTICLE I - DEFINITIONS 

As used in this Agreement the following terms, whether singular or plural, shall have the following meanings: 

A. “Affiliate” shall mean any entity that owns or controls or is owned or controlled by a Party through ownership of more than
fifty percent (50%) of the stock entitled to vote for election of directors of that Party or the maximum percentage of stock interest that a foreign investor may own, whether fifty percent or less, pursuant to the local laws, regulations or
administrative orders of any country, provided the Party exercises a substantial control of general policy of the company. 
 B.
“Net Sales” shall mean with respect to any period for any country in the Territory, the gross receipts, by Targent or its Sublicensees, as applicable, from unrelated Third Parties for sales of Licensed Product, less the following
deductions if actually allowed and allocable to Licensed Product: (i) discounts, credits, rebates, allowances, adjustments, rejections, recalls, and returns for which the customer has been credited as customary to the industry; (ii) trade,
quantity, or cash discounts or rebates customary to the industry and actually allowed, given or accrued (including, but not limited to, cash, governmental and managed care rebates, hospital or other buying group charge backs, and governmental taxes
in the nature of a rebate based on usage levels or sales of the Licensed Product); (iii) sales, excise, turnover, inventory, value-added, and similar taxes assessed on the sale of the Licensed Product; (iv) actual transportation,
distribution, importation, insurance and other handling fees; (v) transfers or dispositions of Licensed Product for charitable, promotional (including samples), or regulatory purposes, and (vi) sales or transfers of Licensed Product among
Targent’s Sublicensees provided that a royalty on that Licensed Product is paid to Strathclyde upon its sale by Targent or its Sublicensee to a Third Party. For the avoidance of doubt, for each Licensed Product the Net Sales shall be calculated
only once for the first sale of such Licensed Product by Targent or its Sublicensees, as the case may be. A sale of Licensed Products by Targent or its Sublicensees to a wholesaler, distributor or any other Third Party shall be regarded as the first
sale of the Licensed Product for the purpose of calculating Net Sales. 
 C. “Effective Date”
shall mean the date indicated first above as the effective date of this Agreement. 
 D. “License” shall mean the
license granted pursuant to Article II of this Agreement. 

  
 26 

 E. “Licensed Patents” shall mean those patents and patent applications in
existence as of the Effective Date and listed in Schedule A, and any divisions, re-issues, continuations and continuations-in-part or their equivalents, and the foreign equivalents thereof in the Territory. 

F. “Licensed Product” shall mean any product made, have made, imported, used, sold, or otherwise disposed of: 

 

	 	i)	which falls within the scope of any claim of any of the unexpired Licensed Patents; 

 

	 	ii)	the manufacture of which requires use of the Licensed Patents; or 

  

	 	iii)	which would, but for the License granted herein, otherwise directly infringe, contributorily infringe or induce the infringement of any of the Licensed Patents.

 G. “Territory” shall mean North America (namely, the United States and its territories and
protectorates, Canada and Mexico). 
 H. “NDA” shall mean a New Drug Application, as defined in the United States
Food, Drug & Cosmetic Act and applicable regulations promulgated thereunder, as amended from time to time, to obtain approval from the FDA for commercial sale of a Licensed Product. 

I. “Third Party” shall mean any person or entity other than a Party or Sublicensee. 

J. “Sublicensee” shall mean any person or entity Targent has a sublicense relationship with in respect of the Licensed Patents.

  
 27 

 ARTICLE II - GRANT OF LICENSE. 

A. Grant of License. 
 As of the Effective Date of this Agreement, Strathclyde hereby grants to Targent during the term of this Agreement and subject to the terms hereof, 

(1) an exclusive license (even as to Strathclyde) under the Licensed Patents to make, have made, import, use and sell the Licensed
Products in the Territory; 
 (2) the right to grant sublicenses to Sublicensees under this Agreement of no greater scope than
the License granted thereunder to Targent and provided that the Sublicensee is subject to the licensee obligations under this Agreement. 
 B. Strathclyde shall have the right to license the Licensed Patents to a Third Party or Third Parties for use outside the Territory. Targent may approach Strathclyde at any time if it wishes a license to
the Licensed Patents outside the Territory. 
 C. Non-Assert Provision. 

During the term of this Agreement Strathclyde will not, 
 (1) assert any of the Licensed Patents to prevent the importation, use or sale of the Licensed Products in the Territory by any Third Party obtaining Licensed Product from Targent or its Sublicensees
pursuant to this Agreement; nor 
 (2) assert any other patent or patent application now or hereafter controlled (in the sense of
having the right to grant licenses or sublicenses) by Strathclyde to prevent the importation, use or sale of the Licensed Product in the Territory by any Third Party obtaining Licensed Product from Targent or its Sublicensees pursuant to this
Agreement. 

  
 28 

 ARTICLE III - PAYMENTS AND REPORTS 

A. Fees. In consideration for the license granted hereunder, Targent shall pay Strathclyde the following fees in U.S. Dollars
(“Fees”): 
  

	 	(1)	Progress Payment (a one-time payment): 

 Within thirty (30) days after NDA approval for the first Licensed Product, a payment of fifty thousand dollars ($50,000). 

 

	 	(2)	Royalties: 

 (i) Targent shall
pay Strathclyde, one percent (1%) of Net Sales of Licensed Product sold in the Territory solely for use in methotrexate therapy from the Effective Date to the date of expiration of Targent’s marketing exclusivity based on the orphan drug
designation of methotrexate use for the Licensed Product. 
 (ii) Targent shall pay Strathclyde, one percent (1%) of Net
Sales of Licensed Product sold in the Territory for uses other than methotrexate therapy where such uses would, in the absence of the licenses granted herein, infringe one or more claims of one or more of the Licensed Patents in force in that part
of the Territory. For the avoidance of doubt, no royalties shall be payable after the expiration of the exclusivity based on the orphan drug designation for each other use. For the further avoidance of doubt, in respect of sales of Licensed Product
for the treatment of colorectal cancer sold in the USA after the date of expiration of U.S. Patent 6,849,628 no royalties shall be payable. 

  
 29 

	 	(3)	Targent shall reimburse Strathclyde for the maintenance fees incurred by Strathclyde for the Licensed Patents during the term of this Agreement.

 If Targent defaults in payment of any fees payable hereunder for more than forty-five (45) days, then without prejudice to
Strathclyde’s other rights and remedies the outstanding amount shall bear interest at the rate of 2% per annum over the base lending rate from time to time of the Royal Bank of Scotland plc from the due date until payment is made.

 B. Reports and Remittances. Until such time as Targent and any Sublicensee has sold all quantities of the Licensed
Product subject to fee hereunder, Targent shall report in writing to Strathclyde within forty-five (45) days after the end of each calendar quarter the quantities of Licensed Product subject to fee hereunder that were sold by Targent and any
Sublicensee during said quarter and the calculation of the fees thereon. With said report Targent shall pay to Strathclyde the total amount of the said fees. If no Licensed Product subject to fee hereunder has been sold by Targent or any Sublicensee
during any such period, Targent shall so report in writing to Strathclyde within forty-five (45) days after the end of such period. Each payment and report and all other reports, notices and other communications to Strathclyde hereunder shall
be sent to: 
  

	
	University of Strathclyde
	 Research and Consultancy Services

	 50 George Street, Glasgow, G1 1ZE,

	 Scotland, United Kingdom

	 Attention: The Director

 Notices to Targent shall be sent to the address set forth above unless a different address is
designated in writing by Targent. 

  
 30 

 C. Taxes. If laws, rules or regulations require withholding of income taxes or other
rates imposed upon payments set forth in this Article III, Targent may make such withholding payments as required and subtract such withholding payments from the payments set forth in this Article III. Targent shall submit appropriate proof of
payment of the withholding rates to Strathclyde within a reasonable period of time. Targent shall use efforts consistent with its usual business practices to ensure that any withholding taxes imposed are reduced as far as possible under the
provisions of the current or any future double taxation treaties or agreements between foreign countries, and the Parties shall cooperate with each other with respect thereto, with the appropriate Party under the circumstances providing the
documentation required under such treaty or agreement to claim benefits thereunder. 
 D. Records. Targent shall keep,
and require each Sublicensee to keep, adequate records in accordance with GAAP in sufficient detail and in the currencies in which the sale was made to enable the fees payable by Targent hereunder to be determined. All such records shall be retained
for three (3) years after the end of the period to which they pertain. 
 E. Audit. If Strathclyde disagrees with a
report provided by Targent pursuant to Article III (B), Strathclyde, at its own expense, shall have the right, upon reasonable prior notice during regular business hours, to meet with Targent’s independent auditors to inspect and discuss the
books and accounts of Targent, related to the payment and calculation of royalties arising under this Agreement. After this inspection, if Strathclyde still disagrees with the report provided by Targent, with reasonable justification for such
disagreement, Strathclyde, at its own expense, shall have the right, upon reasonable prior notice during regular business hours, to appoint independent auditors reasonably acceptable to Targent and have them inspect the books and accounts of Targent
during normal business hours, related to the payment and calculation of royalties arising under this Agreement. The auditors performing the audit shall disclose to Strathclyde only information relating to the accuracy of records kept and the
payments made, and shall be under a duty to keep confidential any other information obtained from such records. If any such audit establishes that Targent or any Sublicensee has underpaid or overpaid the amount due, Targent shall promptly pay any
remaining amounts due as established by such audit or Strathclyde shall promptly refund any over payment. If the underpayment is by six percent (6%) or more during any calendar year, Targent shall reimburse Strathclyde for the reasonable
expenses of such audit. 

  
 31 

 Targent shall secure the right to audit its Sublicensees and shall report to Strathclyde the
results of any such audit related to the payment and calculation of royalties arising under each sublicense. 
 ARTICLE IV - TARGENT
DELIVERABLES 
 A. Government Approvals. In consideration for the licenses granted hereunder, Targent will, at its
cost and expense, seek all governmental approvals required for the making, marketing and sale of Licensed Product in the Territory as soon as practicable. Any and all registrations with the FDA for Licensed Product will be filed in the name of
Targent and shall be owned by Targent. 
 B. Product Marketing. Targent will, at its expense and upon approval of the NDA
for the Licensed Product, begin marketing efforts in the Territory to promote and sell the Licensed Product and will require its Sublicensees to take all reasonable steps to promote and sell the Licensed Product. 

C. Targent Efforts. Targent shall perform its obligations under the Agreement by expending its commercially reasonable efforts by
exercising the same level of effort to promote, advertise and market Licensed Product as it expends for its other respective products with similar sales potential. 
 ARTICLE V - INTELLECTUAL PROPERTY 
 Prosecution of Patents.
Strathclyde shall be solely responsible for preparing, prosecuting and maintaining the Licensed Patents, including payment of all necessary filing and maintenance fees. 
 In the event that Strathclyde wishes to abandon any patent within the Licensed Patents, Strathclyde will offer to assign to Targent, free of any charge or royalty, any such patent prior to effectuating
the abandonment. Targent shall bear the costs connected with any assignment, and recordation thereof, hereunder. 

  
 32 

 ARTICLE VI - THIRD PARTY ACTIONS 

A. If at any time any Third Party shall infringe to a commercially substantial extent any patent licensed hereunder then Targent shall
promptly inform Strathclyde of such infringement and Strathclyde and Targent shall, subject to Paragraph (B) of this Article, either (a) obtain a discontinuance of said infringing operations or (b) bring suit at their own expense
against such infringer, bringing said suit in the name of Strathclyde and, if so required by the law of the forum, bringing suit in the name of Targent or joining Targent as a party plaintiff with Strathclyde. Strathclyde and Targent shall be
entitled to receive their reasonable costs of litigation, Strathclyde shall retain one percent (1%) of the Net Sales of infringing products according to the formula described in Article III(A)(2) and Targent shall receive the remainder of all
recoveries from such infringement. 
 B. In the event that Strathclyde does not participate in such a suit against a Third Party
as provided in paragraph (A) of this Article, then Targent may at its election bring suit in its own name against such infringer. Should Targent bring suit in its own name, Strathclyde shall execute such legal papers necessary for the
prosecution of such suit as may be requested by Targent. Targent shall be liable for all reasonable costs and expenses of such litigation and shall be entitled to receive and retain all recoveries therefrom provided it shall pay to Strathclyde
royalties at the rate of 1% in respect of such recoveries, according to the formula described in Article III(A)(2) (after Targent’s reasonable expenses of such litigation). 

C. If a Third Party makes or threatens against Targent or its Sublicensees any claim of infringement of a patent right based upon the use
of, or arising as a result of the exercise of the rights and licenses granted hereunder to the Licensed Patents (each an “Alleged Infringement”), Targent shall have the right to respond to and defend any and all such Alleged Infringements
at its or their own cost and expense, and in its or their sole discretion. Strathclyde shall provide any necessary assistance that Targent may reasonably require in any such defense action. Strathclyde shall have the right, at its own expense, to
retain counsel of its choice to represent it in any such defense action. Targent shall notify Strathclyde in writing and provide a copy of (i) any claim of Alleged Infringement filed with a court or governmental authority or (ii) any
written notice of an Alleged Infringement from an attorney or law firm. 

  
 33 

 In the event an injunction is issued against Targent because of infringement of Third Party
intellectual property rights, the Parties will confer to decide their future course of action regarding Licensed Products and sharing liability for Targent’s expenses. 
 ARTICLE VII - TERMINATION 
 A. Termination. Unless terminated earlier
as hereinafter provided, and subject to the provisions of paragraph (B) of this Article, this Agreement shall terminate upon the expiration of the last of the patents licensed hereunder. 

B. Early Termination by Targent. Targent may terminate this Agreement at any time by giving Strathclyde at least six
(6) months’ advance written notice. Upon such early termination, all rights granted to Targent under Article II shall revert to Strathclyde. 
 C. Termination upon Breach. In the event that any stipulation or provision of this Agreement is materially breached by a Party, the other Party may terminate this Agreement upon forty-five
(45) days’ written notice to the breaching Party. However, if such breach is corrected within the forty-five (45) day period, and there are no unreimbursed damages resulting from the breach, this Agreement shall continue in force. For
purposes of this Agreement, it is not a “material breach” of this Agreement by Targent if the development or commercialization of a Licensed Product is delayed due to the following: (i) scientific, medical or technical reasons;
(ii) circumstances beyond the control of Targent; (iii) government reimbursement issues; or (iv) the fault of Strathclyde. 

  
 34 

 D. Insolvency. Should Targent (1) become insolvent or unable to pay its debts as
they mature, or (2) make an assignment for the benefit of creditors, or (3) permit or procure the appointment of a receiver for its assets, or (4) become the subject of any bankruptcy, insolvency or similar proceeding, then
Strathclyde may at any time thereafter on written notice to Targent, effective forthwith, cancel this Agreement and any sublicenses granted by Targent pursuant to this Agreement. 

E. Effect of Termination. Upon termination of this Agreement pursuant to Article VII(A), the licenses granted hereunder shall be
considered fully-paid and Targent and its Sublicensees shall be free to continue to make, import, use and sell the Licensed Product without further financial obligation to Strathclyde hereunder. Other than rights intended to survive expiration, or
royalties or fees that accrued during the term of the Agreement in accordance with Article III(A), neither Party shall have any further rights or obligations upon the expiration of this Agreement. Upon termination of this Agreement by Strathclyde
pursuant to Articles VII(C) or (D), or by Targent pursuant to Article VII(B), occurring prior to the regularly scheduled expiration date of this Agreement, all rights and licenses granted by Strathclyde to Targent shall terminate and revert to
Strathclyde. Upon any termination of this Agreement by Targent under Article VII(C) because of Strathclyde’s breach occurring prior to the regularly scheduled expiration date of this Agreement, the license rights granted by Strathclyde to
Targent contained in this Agreement shall continue in full force and effect, however, Targent’s obligations under this Agreement to pay royalties shall terminate. Obligations of the Parties under Articles VII(E) and X(C) and Articles I, IX,
XII, XIV and XV and any other provisions which are expressly indicated to survive expiration or termination, shall remain in effect upon any termination or expiration of this Agreement as shall Targent’s obligations under Articles III(A)(2) for
Licensed Products sold prior to such termination or expiration. 
 For the avoidance of doubt, no additional royalties or fees
of any kinds shall be payable to Strathclyde after the date of expiration of Targent’s marketing exclusivity based on the orphan drug designation of methotrexate rescue for the Licensed Product, except those accrued during the term of the
Agreement in accordance with Article III(A)(2). 

  
 35 

 ARTICLE VIII - ASSIGNABILITY 
 This Agreement shall not be assignable in whole or in part to any Third Party without the prior written consent of the other Party (such consent not to be unreasonably be withheld), except to a successor
in interest pursuant to a merger, acquisition or sale of all or substantially all of the assignor’s assets to which this Agreement relates. Any attempted assignment in violation of this provision shall be null and void.

ARTICLE IX - APPLICABLE LAW 
 This Agreement shall in all respects be construed and interpreted in accordance with, and governed by, the Law of England, and the parties subject to the jurisdiction of the English Courts provided that
all questions concerning the construction or effect of patent applications and patents shall be decided in accordance with the laws of the country in which the particular patent application or patent concerned has been filed or granted, as the case
may be. 
 ARTICLE X - REPRESENTATIONS, WARRANTIES, AND INDEMNIFICATION 

A. Mutual Representations. Each of the Parties represents and warrants that: 

 

	 	(a)	It is a corporation or entity duly organized and validly existing under the laws of the country, state or other jurisdiction of its incorporation or formation.

  

	 	(b)	The execution, delivery, and performance of this Agreement by such Party have been duly authorized by all requisite corporate action. 

  
 36 

	 	(c)	It has the power and authority to execute and deliver this Agreement and perform its obligations hereunder. 

 

	 	(d)	The execution, delivery and performance by such Party of this Agreement does not and will not conflict with or result in breach of the terms and provisions of any other
agreement or constitute a default under (i) a loan agreement, guaranty, financing agreement, affecting a product or other agreement or instrument binding or affecting it or its property; (ii) the provisions of its charter or operative
documents or bylaws; or (iii) any order, writ, injunction or decree of any court or governmental authority entered against it or by which any of its property is bound. 

 

	 	(e)	The execution, delivery and performance of this Agreement by such Party does not require the consent, approval or authorization of, or notice, declaration, filing or
registration with, any governmental or regulatory authority in the Territory and the execution, delivery and performance of this Agreement do not violate any law, rule or regulation applicable to such Party. 

 

	 	(f)	This Agreement has been duly authorized, executed and delivered and constitutes such Party’s legal, valid, and binding obligation enforceable against it in
accordance with its terms subject, as to enforcement, to bankruptcy, insolvency, reorganization and other laws of general applicability relating to or affecting creditors’ rights and to the availability of particular remedies under general
equity principles. 

  

	 	(g)	It shall comply with all applicable laws and regulations relating to its activities under this Agreement. 

  
 37 

 B. Strathclyde Representations 

Strathclyde represents and warrants that, as of the Effective Date: (a) it is the owner of all right, title and interest in and to
the Licensed Patents; (b) it has not received any written notice and, to the best of its knowledge, operating under the Licensed Patents does not infringe the proprietary rights of any Third Party; (c) there are no claims, judgments or
settlements against or owed by Strathclyde, or pending or threatened claims, or litigation, relating to the Licensed Patents; (d) Schedule A is a complete and accurate listing of all patents and patent applications subject to grant hereunder;
and (e) it has not granted any right, license or interest in or to Licensed Patents inconsistent with the rights granted to Targent herein. 
 C. Indemnification 
 Strathclyde shall indemnify and hold Targent and its
Sublicensees harmless from and against any direct liability, loss, cost, expense (including reasonable attorneys’ fees), damage, or penalty of any kind, on account of or resulting from (i) any breach by Strathclyde of its representations
and warranties contained in this Article X, (ii) any breach by Strathclyde of any covenant contained in this Agreement, and (iii) any claim or action for infringement of any Third Party intellectual property rights as a result of
Targent’s operations under the Licensed Patents in the Territory in accordance with this Agreement. Strathclyde’s liability under this Article X(C)(iii) shall be limited to the amount of damages/royalties imposed on Targent by judgment or
settlement upon the finding of infringement or upon a negotiated license and shall be further limited to the amount of Fees paid by Targent to Strathclyde. Strathclyde shall have the right, at any time, to join negotiations with a Third Party whose
intellectual property rights are alleged to be infringed or to take over negotiations with that Third Party if the scope of the alleged infringement is outside the scope of Targent’s operations under this Agreement. 

Targent shall indemnify and shall impose a corresponding indemnity on its Sublicensees to indemnify Strathclyde and hold Strathclyde
harmless from and against any direct liability, loss, cost, expense (including reasonable attorneys’ fees), damage, or penalty of any kind, on account of or resulting from (i) any breach by Targent or its Sublicensees, as the case may be,
of its or their representations and warranties contained in this Article X and (ii) any breach by Targent or its Sublicensees, as the case may be, of any covenant contained in this Agreement. 

  
 38 

 ARTICLE XI - FORCE MAJEURE 
 Neither Party shall be responsible to the other for delay or failure in performance of any of the obligations imposed by this Agreement, provided such delay or failure shall be occasioned by a cause
beyond the control of and without the fault or negligence of such Party, including fire, flood, explosion, lightning, windstorm, earthquake, subsidence of soil, failure of machinery or equipment or supply of materials, discontinuity in the supply of
power, court order or governmental interference, civil commotion, riot, war, terrorism or terroristic threats, strikes, labor disturbances, transportation difficulties or labor shortage. 
 ARTICLE XII - DISPUTE RESOLUTION. 
 In the event that a dispute arises
between the Parties, the following procedures shall be followed: 
 A. Negotiations. In the event that any dispute may
arise, the Parties shall first seek to resolve any disputes by negotiation among senior executives who have authority to settle the controversy, as follows: 
  

	 	(d)	Notification. When a Party believes there is a dispute relating to the Agreement, the Party will give the other Party written notice of the dispute.

  

	 	(e)	Meeting Among Senior Executives. The senior executives shall meet (either in person or via a video or telephone conference) at a mutually acceptable time and
place within thirty (30) days after the date of the notice to exchange relevant information and to attempt to resolve the dispute. 

  
 39 

	 	(f)	Confidentiality. All negotiations are confidential, shall be treated as compromise and settlement negotiations, and neither Party shall use information obtained
during such negotiations in any subsequent dispute resolution proceeding. 

 B. Mediation. If the dispute
has not been resolved within thirty (30) days after the date of the notice of a dispute, or if the Party receiving such notice fails or refuses to meet within such time period, either Party may initiate mediation of the dispute by sending the
other Party a written request that the dispute be mediated. The Party receiving such a written request will promptly respond to the requesting Party so that both Parties can jointly select a neutral and impartial mediator and schedule the mediation
session. The Parties shall mediate the dispute before a neutral, third-party mediator within thirty (30) days after the date of the written request for mediation. 
 C. Arbitration. Any controversy or claim arising out of or relating to this Agreement, or the breach thereof, and not settled as described in this Article XII (A) or (B), shall be settled by
arbitration in accordance with the Licensing Agreement Arbitration Rules of the International Chamber of Commerce, utilizing the laws of England. The situs of arbitration shall be Glasgow, Scotland if initiated by Targent and Princeton, New Jersey
if initiated by Strathclyde. 
 ARTICLE XIII - ADJUDICATION OF LICENSED PATENTS 

Should any Licensed Patents be declared invalid or not infringed or limited in scope by a final decision (from which no appeal is or can
be taken) of a court or other tribunal of competent jurisdiction in the country in which said patent was granted, then the construction placed upon the patent by said court or other tribunal shall be followed by the Parties from and after the date
of entry of the decree of said court or tribunal and fees shall thereafter be payable to Strathclyde only in accordance with such construction. 

  
 40 

 ARTICLE XIV - CONFIDENTIALITY 

The Parties contemplate that during the course of their relationship it may be necessary for Targent to provide Strathclyde with certain
confidential information (including financial and sales data not otherwise available to the public) to facilitate the performance of its obligations pursuant to this Agreement. Confidential information received from Targent shall be maintained by
Strathclyde in confidence and reasonable and prudent practices shall be followed to maintain the information in confidence and shall be used only for the purpose of and in connection with its performance under this Agreement. The obligation to
maintain information in confidence shall survive this Agreement or termination thereof for any reason for a period of seven (7) years thereafter. 
 ARTICLE XV - MISCELLANEOUS PROVISIONS 
 A. The rights and remedies provided
in this Agreement are cumulative and not exclusive of any rights or remedies provided by law or in equity. 
 B. Except as may
be required by law, rule or regulation that applies to that party, neither Strathclyde nor Targent shall make any public statement or other disclosure of the existence or terms of this Agreement without the express prior written consent of the other
Party as to the nature and substance of such statement or other disclosure. 
 C. This Agreement embodies the entire
understanding of the Parties and shall supersede all previous communications, representations, undertakings or agreements, between them, either verbal or written, relating to the subject matter hereof. 

D. This Agreement shall be binding upon and inure to the benefit of the successors, permitted assignees and personal representatives of
the Parties. 

  
 41 

 E. In the event that any one or more of the provisions contained in this Agreement shall for
any reason be held to be invalid, illegal or unenforceable in any respect, such invalidity, illegality or unenforceability shall not affect any other provision hereof, and this Agreement shall be construed as if such invalid, illegal or
unenforceable provisions or provisions had never been contained herein. 
 IN WITNESS WHEREOF, the Parties have executed this
Agreement and have entered the effective date on the first page hereof. 
  

			
	University of Strathclyde
		
	 By
	 	  

	Title	 	Deputy Director, Head of Grants and Contracts Section
	 Date
	 	
	
	 Targent Incorporated

		
	 By
	 	  

	 Title
	 	 President

	 Date
	 	

  
 42 

 SCHEDULE A 

 

					
	 	  	Patent No.	  	Normal Expiry Date
	 Country
	  	 (Patent Application No.)
	  	 (Filing Date)

	USA	  	4,959,472	  	25th September 2007
		  	(07/403,917)	  	(1st September 1989)
			
	USA	  	6,500,829	  	31st December 2019
		  	(08/426,458)	  	(18th April 1995)
			
	USA	  	6,849,628	  	11th May 2008
		  	(10/228,820)	  	(27th August 2002)
			
	Canada	  	1,339,368	  	26th August 2014
		  	(546105)	  	(3rd September 1987)

  
 43

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