Document:

Master Services Agreement

 Exhibit 10.1 
 MASTER SERVICES AGREEMENT 
 This Master Services Agreement (this
“Agreement”), effective as of the 22nd day of April 2011 (the “Effective Date”), is entered into by and between: Pro-Pharmaceuticals, Inc., a company incorporated under the laws of the State of Nevada, USA, with its principal
office located at 7 Wells Avenue, Suite 34, Newton, MA 02459 (“Company”); and Sigma-Aldrich, Inc., a company incorporated under the laws of the State of Wisconsin, USA (“SAFC”). Company and SAFC are hereinafter sometimes referred
to separately as a “Party” or together as the “Parties”. 
 RECITALS 

WHEREAS, Company is a development-stage company engaged in the discovery, development, and commercialization of
first-in-class, targeted therapeutic compounds for advanced treatment of cancer, liver, and inflammatory diseases; 

WHEREAS, SAFC develops, manufactures and sells a broad range of chemical compounds globally as key components in high technology
manufacturing; 
 WHEREAS, Company desires to engage SAFC, from time to time, to provide services for individual
projects in accordance with mutually agreed upon Work Orders (as discussed below) specifying the details of the services and the related terms and conditions. 
 NOW, THEREFORE, in consideration of the above premises and the mutual covenants and agreements contained herein, the Parties hereby agree as follows: 

 

	1.0	SCOPE OF THE AGREEMENT; WORK ORDERS; NATURE OF SERVICES; 

  

	 	(a)	SCOPE OF AGREEMENT. 

 As a
“master” form of contract, this Agreement allows the parties to contract for multiple projects through the issuance of multiple Work Orders (as discussed in Section 1(b) below), without having to re-negotiate the basic terms and
conditions contained herein. This Agreement covers the provision of services by SAFC and SAFC corporate affiliates (see Section 13) and, accordingly, this Agreement represents a vehicle by which Company can efficiently contract with SAFC and
its corporate affiliates for a broad range of services. 
  

	 	(b)	WORK ORDERS. 

 The
specific details of each project under this Agreement (each “Project”) shall be separately negotiated and specified in writing on terms and in a form acceptable to the parties (each such writing, a “Work Order”). A sample Work
Order is attached hereto as Exhibit A. Each Work Order will include, as appropriate, the scope of work, time line, and budget and payment schedule. Each Work Order shall be subject to all of the terms and conditions of this Agreement, in addition to
the specific details set forth in 

 
the Work Order. To the extent any terms or provisions of a Work Order conflict with the terms and provisions of this Agreement, the terms and provisions of this Agreement shall control, except to
the extent that the applicable Work Order expressly and specifically states an intent to supersede the Agreement on a specific matter. All Work Orders and other exhibits hereto shall be deemed to be incorporated herein by reference. 

 

	 	(c)	NATURE OF SERVICES. 

 The
services covered by this Agreement may include strategic planning, expert consultation, clinical trial services, statistical programming and analysis, data processing, data management, regulatory, clerical, project management, central laboratory
services, pre-clinical services, pharmaceutical sciences services, medical device services, and other research and development services requested by Company and agreed to by SAFC as set forth in the relevant Work Order (collectively, the
“Services”). SAFC and Company, where appropriate, shall cooperate in the completion of a Transfer of Obligations Form in conjunction with the relevant Work Order. Any responsibilities not specifically transferred in the Transfer of
Obligations Form shall remain the regulatory Responsibility of Company. The obligations that have been transferred to SAFC will be provided in a 1571 form to the FDA. 
  

	2.0	PAYMENT OF FEES AND EXPENSES. 

 Company will pay SAFC for fees, expenses and pass-through costs in accordance with the budget and payment schedule contained in each Work Order. Company agrees that the budget and payment schedule for
each Work Order will be structured in an effort to maintain cash neutrality for SAFC (with respect to the payment of professional fees, pass-through costs and otherwise). Company agrees that a prepayment may be necessary for SAFC to maintain cash
neutrality over the term of the Work Order taking into account payment terms agreed upon between the parties (see Work Order for details and terms). Unless otherwise agreed in a particular Work Order, the following shall apply: (a) SAFC will
invoice Company monthly for the fees, expenses and pass-through costs incurred in performing the Services; and, (b) Company shall pay each invoice within thirty (30) days of the date of the invoice. If any portion of an invoice is
disputed, then Company shall pay the undisputed amounts as set forth in the preceding sentence and the parties shall use good faith efforts to reconcile the disputed amount as soon as practicable. Company shall pay SAFC interest in an amount equal
to one percent (1%) per month of all undisputed amounts owing hereunder and not paid within thirty (30) days of the date of the invoice. 
  

	3.0	TERM. 

 This Agreement
shall commence on the date it has been signed by all parties and shall continue for a period of three (3) years from the date of execution, or until terminated by either party in accordance with Section 16 below. 

	4.0	CHANGE ORDERS. 

 Any
(a) change in the details of a Work Order, even if a fixed price Work Order, or (b) change in the assumptions upon which the Work Order is based (including, but not limited to, changes in an agreed starting date for a Project or suspension
of the Project by Company) may require changes in the budget and/or time lines, and shall require a written amendment to the Work Order (a “Change Order”) – see Exhibit B. Each Change Order shall detail the requested changes to the
applicable task, responsibility, duties, budget, time line or other matters. The Change Order will become effective upon the execution of the Change Order by both parties, and will include a specified period of time (as agreed upon by the parties)
within which SAFC will implement the changes. Both parties agree to act in good faith and promptly when considering a Change Order requested by the other party. SAFC reserves the right to postpone effecting material changes in the Project’s
scope until such time as the parties agree to execute the corresponding Change Order. For any Change Order that affects the scope of the regulatory obligations that have been transferred to SAFC, SAFC and Company- shall execute a corresponding
amendment to the Transfer of Obligations Form. Company shall provide such changes to the FDA on the 1571 form and will file such amendment where appropriate, or as required by law or regulation. 

 

	5.0	CONFIDENTIALITY. 

 It is
understood that during the course of this Agreement, SAFC and its employees may be exposed to data and information (hereinafter “Company Confidential Information”) written or verbal, tangible or intangible, made available, disclosed, or
otherwise made known to SAFC and its employees as a result of Services under this Agreement, shall be considered confidential and shall be considered the sole property of Company. All information regarding SAFC’ operations, methods, and pricing
and all SAFC Property (as defined in Section 6.0 below), disclosed by SAFC to Company in connection with this Agreement is proprietary, confidential information belonging to SAFC (the “SAFC Confidential Information”, and together with
the Company Confidential Information, the “Confidential Information”). The Confidential Information shall be used by the receiving party and its employees only for purposes of performing the receiving party’s obligations hereunder.
Each party agrees that it will not reveal, publish or otherwise disclose the Confidential Information of the other party to any third party without the prior written consent of the disclosing party. Each party agrees that it will not disclose the
terms of this Agreement or any Work Order to any third party without the prior written consent of the other party, which shall not unreasonably be withheld. These obligations of confidentiality and nondisclosure shall remain in effect for a period
of five (5) years after the completion or termination of the applicable Work Order. 
 The foregoing obligations shall not
apply to Confidential Information to the extent that it: (a) is or becomes generally available to the public other than as a result of a disclosure by the receiving party; (b) becomes available to the receiving party on a non-confidential
basis from a source which is not prohibited from disclosing such information; (c) was developed independently of any disclosure by the disclosing party or was known to the receiving party prior to its receipt from the disclosing party, as shown
by contemporaneous written evidence; or, (d) is required by law or regulation to be disclosed, provided however that the other party is promptly notified in writing of such requirement prior to, if practicable, disclosure and given an
opportunity to obtain a suitable protective order. 

	6.0	OWNERSHIP AND INVENTIONS. 

All data, information, inventions, improvements in know-how, new uses, processes and compounds relating to the subject drug(s) and or
products(s) covered by this Agreement and/or applicable Work Orders that are conceived, generated, derived, or reduced to practice by SAFC as the result of the Services performed by SAFC under this Agreement shall be and remain the exclusive
property of Company and SAFC agrees to assign its rights in all such inventions and/or related patents to Company. Notwithstanding the foregoing, Company acknowledges that SAFC possesses certain inventions, processes, know-how, trade secrets,
improvements, other intellectual properties and other assets, including but not limited to analytical methods, procedures and techniques, procedure manuals, personnel data, financial information, computer technical expertise and software, which have
been independently developed by SAFC and which relate to its business or operations (collectively “SAFC’ Property”). Company and SAFC agree that any SAFC Property or improvements thereto which are used, improved, modified or developed
by SAFC under or during the term of this Agreement are the sole and exclusive property of SAFC. 
  

	7.0	RECORDS AND MATERIALS. 

At the completion of the Services by SAFC, all materials, information and all other data owned by Company, regardless of the method of
storage or retrieval, shall be delivered to Company in such form as is then currently in the possession of SAFC, subject to the payment obligations set forth in Section 2 herein. Alternatively, at Company’s written request, such materials
and data may be retained by SAFC for benefit of the Company for an agreed-upon time period, or disposed of pursuant to the written directions of Company. Company shall pay the costs associated with any of the above options and shall pay a
to-be-determined fee for storage by SAFC of records and materials after completion or termination of the Services. SAFC, however, reserves the right to retain, at its own cost and subject to the confidentiality provisions herein, one copy of all
materials for its corporate files. Nothing in this Agreement shall be construed to transfer from Company to SAFC any FDA or regulatory record-keeping requirements unless such transfer is specifically provided for in the applicable Transfer of
Obligations Form. 
  

	8.0	INDEPENDENT CONTRACTOR RELATIONSHIP. 

 Except as provided in Article 10.0 herein, for the purposes of this Agreement, the parties hereto are independent contractors and nothing contained in this Agreement shall be construed to place them in
the relationship of partners, principal and agent, employer/employee or joint venturers and neither party shall have the power or right to bind or obligate the other party or shall hold itself out as having such authority. If, however, Company
desires to conduct clinical trials in one or more countries that require a local company or representative, and Company does not have an office in those countries, then Company may request that SAFC or its affiliates serve as its agent for that
purpose, and the parties will include in the Work Order an attachment regarding local representative duties. 

	9.0	REGULATORY COMPLIANCE; INSPECTIONS. 

 SAFC agrees that its Services will be conducted in compliance with ICH Guidelines, Good Clinical Practices (GCP), Good Manufacturing Practices, (GMP) all applicable laws, rules and regulations, including
but not limited to the Federal Food, Drug and Cosmetic Act and the regulations promulgated pursuant thereto, and with the standard of care customary in the contract research organization industry. SAFC standard operating procedures will be used in
performance of the Services, unless otherwise specifically stated in the Work Order. SAFC certifies that it has not been debarred by the FDA pursuant to Section (a) or (b) of 21 U.S.C. Section 335a, and that it will not knowingly
employ any person or entity that has been so debarred to perform any Services under this Agreement. Company represents and certifies that it will not require SAFC to perform any assignments or tasks in a manner that would, or potentially would
violate any applicable law or regulation or scientific standard. Company further represents that it will cooperate with SAFC in taking any actions that SAFC reasonably believes are necessary to comply with the regulatory obligations that have been
transferred to SAFC. 
 Each party acknowledges that the other party may respond independently to any regulatory correspondence
or inquiry in which such party or its affiliates are named. Company may review and approve SAFC responses with respect to Company’s study or Project, but such approval shall not be unreasonably withheld. Each party, however, shall: a) notify
the other party promptly of any FDA or other governmental or regulatory inspection or inquiry concerning any study or Project of Company in which SAFC is providing Services, and such inspection or inquiry relates to or affects such Services,
including but not limited to; inspections of investigational sites or laboratories; b) forward to the other party copies of any correspondence from any regulatory or governmental agency relating to such a study or Project, including, but not limited
to; FDA Form 483 notices, and FDA refusal to file, rejection or warning letters, even if they do not specifically mention the other party; and, c) obtain the written consent of the other party, which will not unreasonably be withheld, before
referring to the other party or any of its affiliates in any regulatory correspondence. Where reasonably practicable, each party will be given the opportunity to have a representative present during an FDA or regulatory inspection. Each party,
however, acknowledges that it may not direct the manner in which the other party fulfills its obligations to permit inspection by governmental entities. 
 Each party agrees that, during an inspection by the FDA or other regulatory authority, concerning any study or Project of Company in which SAFC is providing Services, it will not disclose information and
materials that are not required to be disclosed to such agency, without the prior written consent of the other party, which consent shall not unreasonably be withheld. Such information and materials includes, but are not limited to, the following:
1) financial data and pricing data (including, but not limited to, the budget and payment sections of the Work Order); 2) sales data (other than shipment data); and 3) personnel data (other than data as to qualification of technical and professional
persons performing functions subject to regulatory requirements.) 

 During the term of this Agreement, SAFC will permit Company’s representatives (unless
such representatives are competitors of SAFC) to examine or audit the work performed hereunder and the facilities at which the work is conducted upon reasonable advance notice during regular business hours to determine that the Project assignment is
being conducted in accordance with the agreed task and that the facilities are adequate. All information disclosed, revealed to or ascertained by Company in connection with any such audit or examination or in connection with any correspondence
between SAFC and any regulatory authorities (including any FDA Form 483 notices) shall be deemed to constitute SAFC Confidential Information for purposes of this Agreement. Company shall reimburse SAFC for its time and expenses (including reasonable
attorney fees and the costs of responding to findings) associated with any inspection, audit or investigation relating to the Services (“Inspection”) instigated by Company or by a governmental authority, unless such Investigation finds
that SAFC breached this Agreement or any applicable law or regulation (see Work Order for details and terms). 
  

	10.0	INDEMNITY. 

 Company shall
indemnify and hold SAFC and its affiliates harmless and forever release and discharge SAFC and its affiliates from and against all losses, liabilities, damages and expenses (including attorneys’ fees and costs) (“Losses”) that SAFC
and its affiliates may suffer or incur as a result of any claims, demands, actions or other proceedings made or instituted by a third party to which SAFC is or may become subject insofar as they arise out of, or alleged or claimed to arise out of
(a) any injury to or death of any person participating in any project or study, (b) the negligence or intentional misconduct of Company or its affiliates, or its or their directors, officers, employees or agents, (c) any breach of
this Agreement or any Work Order by Company or its affiliates, or its or their directors, officers, employees or agents; (d) any theory of product liability (including, without limitation, actions in the form of tort, warranty or strict
liability), (e) any patent infringement action relating, to Company’s compounds or products, or (f) the use or consumption of any compound or product by Company or any third party. 

SAFC shall indemnify Company and its affiliates from and against all losses, liabilities, damages and expenses (including reasonable
attorneys’ fees and costs) that Company and its affiliates may suffer or incur as a result of any claims, demands, actions or other proceedings made or instituted by a third party against any of them arising out of or relating to the Services
performed under this Agreement or any Work Order to the extent that such claims, demands, actions or other proceedings directly result from (a) any material breach of SAFC of its obligations under this Agreement, or (b) the gross
negligence, recklessness or intentional acts or omissions of SAFC. 
  

	11.0	PROCEDURE. 

 The party that intends to
claim indemnification under this Article (the “Indemnitee”) shall promptly notify the indemnifying party (the “Indemnitor”) for any loss, claim, damage, liability or action with respect to which the Indemnitee intends to claim
such indemnification, and the Indemnitor shall assume the defense thereof with counsel mutually satisfactory to the Indemnitee whether or not such loss, claim, damage, liability or action is rightfully brought; provided, however, that an Indemnitee
shall have the right to retain its own counsel, with the fees and 

 
expenses to be paid by the Indemnitor if Indemnitor does not assume the defense, or, if representation of such Indemnitee by the counsel retained by the Indemnitor would be inappropriate due to
actual or potential differing interests between such Indemnitee and any other person represented by such counsel in such proceedings. The indemnity agreement in this Article shall not apply to amounts paid in settlement of any loss, claim, damage,
liability or action, if such settlement is effected without the consent of the Indemnitor, which consent shall not be withheld or delayed unreasonably. The failure to deliver notice to the Indemnitor within a reasonable time after the commencement
of any such action, only if prejudicial to its ability to defend such action, shall relieve such Indemnitor of any liability to the Indemnitee under this Article, but the omission to deliver notice to the Indemnitor will not relieve it of any
liability that it may have to any Indemnitee otherwise than under this Article. The Indemnitor shall not settle the action or otherwise consent to an adverse judgment in such action that diminishes the rights or interest of the Indemnitee without
the express consent of the Indemnitee. The Indemnitee under this Article, its employees and agents, shall cooperate fully with the Indemnitor and its legal representatives in the investigations of any action, claim or liability covered by this
indemnification. The Indemnitee shall keep the Indemnitor informed of any investigation and the Indemnitor shall have the right to review and comment on the conduct of the investigation. 
 LIMITATION OF LIABILITY. 
 NEITHER PARTY SHALL BE LIABLE TO THE OTHER
PARTY FOR INDIRECT, INCIDENTAL OR CONSEQUENTIAL DAMAGES (SUCH AS LOST PROFITS) OR ANY SPECIAL OR PUNITIVE DAMAGES ARISING OUT OF THE PERFORMANCE OF THIS AGREEMENT, WHETHER BASED ON CONTRACT, NEGLIGENCE, STRICT LIABILITY, OTHER TORT OR OTHERWISE AND
REGARDLESS OF WHETHER ANY PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES 
 THE MAXIMUM AGGREGATE LIABILITY OF SAFC
TO COMPANY FOR ANY CAUSE OF ACTION (OR RELATED CAUSES OF ACTION) ARISING OUT OF OR RELATED TO THIS AGREEMENT AND THE DELIVERY OF THE PRODUCT OR SERVICE SHALL NOT EXCEED THE AMOUNT PAID BY COMPANY TO SAFC PURSUANT TO THIS AGREEMENT FOR THE PRODUCT OR
SERVICE DURING THE TWELVE (12) MONTH PERIOD IMMEDIATELY PRECEDING THE CLAIM GIVING RISE TO THE LIABILITY. 
 COMPANY INSURANCE.

 Without limiting its liability under this Agreement (except as may be otherwise expressly provided in this Agreement),
during the Term and for five (5) years after the expiration or termination of this Agreement, Company shall obtain and maintain commercial general liability/product liability insurance with limits of not less than $10,000,000 per occurrence for
general liability and product liability. With respect to all insurance coverage required under this Section (i) Company shall, promptly upon SAFC’s request, furnish SAFC with certificates of insurance evidencing such insurance and
(ii) all policies shall include provisions for at least thirty (30) days’ prior written notice of cancellation. SAFC shall be named as an additional insured under the policies of insurance required by this Section. 

 SAFC INSURANCE. 
 Without limiting its liability under this Agreement (except as may be otherwise expressly provided in this Agreement), during the Term and for five (5) years after the expiration or termination of
this Agreement, SAFC shall obtain and maintain commercial general liability/product liability insurance with limits of not less than $10,000,000 per occurrence for general liability and product liability. With respect to all insurance coverage
required under this Section (i) SAFC shall, promptly upon Company’s request, furnish Company with certificates of insurance evidencing such insurance and (ii) all policies shall include provisions for at least thirty
(30) days’ prior written notice of cancellation. 
 DISCLAIMER. 
 EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, THE PARTIES MAKE NO REPRESENTATIONS OR WARRANTIES OF ANY KIND WHATSOEVER, EITHER EXPRESS OR IMPLIED, WRITTEN OR ORAL, INCLUDING WITHOUT LIMITATION ANY
IMPLIED WARRANTY OF MERCHANTABILITY, WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE, OR WARRANTY OF NON-INFRINGEMENT 
 12.0 TERMINATION.

 Company may terminate this Agreement or any Work Order without cause at any time during the term of the Agreement on
forty-five (45) days’ prior written notice to SAFC. Either party may terminate this Agreement or any Work Order for material breach upon thirty (30) days’ written notice specifying the nature of the breach, if such breach has not
been substantially cured within the thirty (30) day period. During the 30-day cure period for termination due to breach; each party will continue to perform its obligations under the Agreement. If the termination notice is not due to a breach,
or if the cure period has expired without a substantial cure of the breach, then the parties shall promptly meet to prepare a close out schedule, and SAFC shall cease performing all work not necessary for the orderly close out of the Services or
required by laws or regulations. Either party may terminate this Agreement or any Work Orders immediately upon provision of written notice if the other party becomes insolvent or files for bankruptcy. Any written termination notice shall identify
the specific Work Order or Work Orders that are being terminated. 
 If this Agreement or any Work Order is terminated, Company
shall pay SAFC for all Services performed in accordance with this Agreement to the date of termination, and any applicable Work Order (see Work Order for details and terms) and reimburse SAFC for all costs and expenses incurred in performing those
Services, including all non-cancelable costs incurred prior to termination but paid after the termination date. Company shall pay for all the work actually performed in accordance with this Agreement and the applicable Work Order, even if the
parties’ original payment schedule spreads-out payments for certain services (examples are unit or milestone-based payments) or defers payments for certain services until the end of the Study. Company shall pay for all actual costs, including
time spent by SAFC personnel (which shall be billed at SAFC standard daily rates in effect as of the date of the termination notice), 

 
incurred to complete activities associated with the termination and close-out of affected Projects, including the fulfillment of any regulatory requirements. In addition, if the termination is by
Company without cause, or by SAFC for cause, and the total fees for the Project are greater than one million U.S. dollars in value, then Company shall pay to SAFC an amount equal to twenty percent (20%) of the budget for the remainder of
Services that have not yet been performed, to cover SAFC’ costs associated with early termination (see Work Order for details and terms). 
  

	13.0	RELATIONSHIP WITH AFFILIATES. 

 Company agrees that SAFC may use the Services of its corporate affiliates, subject to prior written consent by the Company, to fulfill SAFC obligations under this Agreement and any Work Order. Any
affiliate so used shall be subject to all of the terms and conditions applicable to SAFC under this Agreement or any Work Order, entitled to all rights and protections afforded SAFC under this Agreement or any Work Order. SAFC agrees that
Company’s affiliates may use the services of SAFC (and its affiliates) under this Agreement. In such event, such Company’s affiliates shall be bound by all the terms and conditions of this Agreement and any Work Order and entitled to all
rights and protections afforded Company under this Agreement and any Work Order. The term “affiliate” shall mean all entities controlling, controlled by or under common control with Company or SAFC, as the case may be. The term
“control” shall mean the ability to vote fifty percent (50%) or more of the voting securities of any entity or otherwise having the ability to influence and direct the policies and direction of an entity. 

 

	13.0	COOPERATION; COMPANY DELAYS; DISCLOSURE OF HAZARDS. 

 Company shall forward to SAFC in a timely manner all documents, materials and information in Company’s possession or control necessary for SAFC to conduct the Services. SAFC shall not be liable to
Company nor be deemed to have breached this Agreement or any Work Order, for errors, delays or other consequences arising from Company’s failure to timely provide documents, materials or information or to otherwise cooperate with SAFC in order
for SAFC to timely and properly perform its obligations. If Company delays a project from its agreed starting date or suspends performance of a project for a period longer than fifteen (15) working days, then either: a) Company will pay the
standard daily rate of the SAFC’ personnel assigned to the project, based on the percentage of their time allocated to the project, for the period of the delay beginning on the eleventh working day, in order to keep the Current team members;
or, b) SAFC may re-allocate the personnel at its discretion, and Company will pay the costs of retraining new personnel. In addition, Company will pay all non-cancelable costs and expenses incurred by SAFC due to the delay and will adjust all
timelines to reflect additional time required due to the delay. Company shall provide SAFC with all information available to it regarding known or potential hazards associated with the use of any substances supplied to SAFC by Company, and Company
and SAFC shall comply with all current legislation and regulations concerning the shipment of substances by the land, sea or air. 
  

	14.0	FORCE MAJEURE. 

 In the
event either party shall be delayed or hindered in or prevented from the performance of any act required, hereunder by reasons of strike, lockouts, labor troubles, inability to procure 

 
materials or services, failure of power or restrictive government or judicial orders or decrees, riots, insurrection, war, Acts of God, inclement weather or other reason or cause beyond that
party’s control, then performance of such act (except for the payment of money owed) shall be excused for the period of such delay. 
  

	15.0	NOTICES AND DELIVERIES. 

Any notice required or permitted to be given hereunder by either party hereunder shall be in writing and shall be deemed given on the date
received if delivered personally or by a reputable overnight delivery service, or three (3) days after the date postmarked if sent by registered or certified mail, return receipt requested, postage prepaid to the following addresses:

  

							
	If to SAFC.	  		  	If to Company:	  	
	SAFC	  		  	Pro-Pharmaceuticals, Inc.
	3050 Spruce Street	  		  	7 Wells Avenue, Suite 34	  	
	St. Louis, Missouri 63103	  		  	Newton, MA 02459	  	
			
	Attention:                 Legal Department	  	Attention:	  	Maureen E. Foley
		  		  	Chief Operating Officer
			
	With a copy to:             Tom Gelineau	  	 With a copy to:

Address as above
	  	
		  		  	Attention:	  	Anthony Squeglia
		  		  		  	Chief Financial Officer

 If Company delivers, ships, or mails
materials or documents to SAFC, or requests that SAFC deliver, ship, or mail materials or documents to Company or to third parties, then the expense and risk of loss for such deliveries, shipments, or mailings shall be borne by Company, provided
that SAFC followed Company’s written instructions for the materials that were delivered, shipped, or mailed. SAFC disclaims any liability for the actions or omissions of third party delivery services or carriers. 

 

	17.0	INFLATION ADJUSTMENTS. 

Where services in a Work Order are provided by SAFC over multiple calendar years, SAFC may increase its fees at the beginning of each
calendar year to reflect increases in SAFC’ business costs on a prospective basis only. SAFC’ overall cost increase for the next twelve (12) month period shall not exceed the percentage charge in the wages/earnings survey as published
in the Economist (or as reported at WWW.ECONOMIST.COM) or the equivalent inflation index of the country where services are performed over the preceding twelve (12) month period (see Work Order for details and terms). 

	18.0	BINDING AGREEMENT AND ASSIGNMENT. 

 Except as stated above in Section 13, neither party may assign any of its rights or obligations under this Agreement to any party without the express, written consent of the other party; provided,
however, that without such consent, either party may assign this Agreement in connection with the transfer or sale of all or substantially all of its assets, stock or business, or its merger with another entity, provided further, however, the
assignee has the financial ability to fulfill assignor’s obligations hereunder. Subject to the foregoing, this Agreement shall be binding upon, inure to the benefit of and be enforceable by the parties and their respective successors and
permitted assigns. 
  

	19.0	CHOICE OF LAW, WAIVER AND ENFORCEABILITY. 

 This Agreement shall be construed, governed, interpreted, and applied in accordance with the laws of the State of Missouri, exclusive of its conflicts of law provisions. The failure to enforce any right
or provision herein shall not constitute a waiver of that right or provision. Any waiver of a breach of a provision shall not constitute a waiver of any subsequent breach of that provision. If any provisions herein are found to be unenforceable on
the grounds that they are overly broad or in conflict with applicable laws, it is the intent of the parties that such provisions be replaced, reformed or narrowed so that their original business purpose can be accomplished to the extent permitted by
law, and that the remaining provisions shall not in any way be affected or impaired thereby. 
  

	20.	SURVIVAL. 

 The rights and
obligations of Company and SAFC, which by intent or meaning have validity beyond such termination (including, but not limited to, rights with respect to inventions, confidentiality, discoveries and improvements, indemnification and liability
limitations) shall survive the termination of this Agreement or any Work Order. 
  

	21.0	ARBITRATION. 

 Any
controversy or claim arising out of or relating to this Agreement or the breach thereof may be settled by arbitration administered by the American Arbitration Association (“AAA”) under its Commercial Arbitration Rules, and judgment on the
award rendered by the arbitrator shall be binding and may be entered in any court having jurisdiction thereof. If arbitration is demanded by SAFC, such arbitration shall take place in St. Louis, Missouri and if demanded by Company, in Boston MA.
Such arbitration shall be conducted in English by one arbitrator mutually acceptable to the parties selected in accordance with AAA rules. The arbitrator shall not have the power to award any punitive damages or any damages excluded by this
Agreement. 
  

	22.0	ENTIRE AGREEMENT, HEADINGS AND MODIFICATION. 

 This Agreement, together with the applicable Work Orders, contains the entire understandings of the parties with respect to the subject matter herein, and supersedes all

 
previous agreements (oral and written), negotiations and discussions. The descriptive headings of the sections of this Agreement are inserted for convenience only and shall not control or affect
the meaning or construction of any provision hereof. Any modifications to the provisions herein must be in writing and signed by the parties. 

{Signature page follows} 

 IN WITNESS WHEREOF, THIS AGREEMENT has been executed by the parties hereto through
their duly authorized officers on the date(s) set forth below. 
 ACKNOWLEDGED, ACCEPTED AND AGREED TO: 

 

									
	SIGMA-ALDRICH, INC.	 		 	PRO-PHARMACEUTICALS, INC.
	3050 Spruce Street	 		 	7 Wells Avenue, Suite 34
	St. Louis, Missouri 63103	 		 	Newton, MA 02459
					
	By:	 	 /s/ Gilles Cottier
	 		 	By:	 	 /s/ Peter G. Traber

					
	Print Name:	 	 Gilles Cottier
	 		 		 	 Peter G. Traber, M.D.

					
	Title:	 	 Executive Vice President
	 		 	Title:	 	 Chief Executive Officer

					
	Date:	 	 4-22-11
	 		 	Date:	 	 4-22-11FORM OF NON-QUALIFED STOCK OPTION

 Exhibit 10.1 
 CryoLife, Inc. 
 1655 Roberts Boulevard, N.W. 

Kennesaw, GA 30144 
 (770) 419-3355 – (800) 438-8285 

Date:__________ 
 Name:
                                  

Address:
                              
                                  
             
  

	Re:	Grant of Non-Qualified Stock Option Pursuant to CryoLife, Inc. 

	  	2002 Stock Incentive Plan (the “Plan”) 

Dear ____________: 
 This letter
sets forth the agreement between you and CryoLife, Inc., a Florida corporation (the “Corporation”), regarding your option to acquire shares of the Corporation’s Common Stock. 

1. Grant of Option. Subject to the terms set forth below, the Corporation hereby grants to Employee the right, privilege, and
option to purchase up to              shares (the “Option Shares”) of its Common Stock at the purchase price of
$             per share, which price is equal to the closing price of the Corporation’s Common Stock on the New York Stock Exchange on
                    . The date of grant (“Grant Date”) of the option is
                    . This option is not intended to be and shall not be treated as an “Incentive Stock Option,” as that term is
defined in Section 422 of the Internal Revenue Code of 1986, as amended. 
 2. Time of Exercise of Option. Prior to
its termination as set forth in Section 5 below, this option shall vest, and the Employee may exercise the option granted herein on a cumulative basis as described below: 

					
	 Exercise Date
	  	
Cumulative Percentage of
Option Shares Exercisable
	 
		
		  			
		  	 	 	 
		  			
		  	 	 	 
		  			
		  	 	 	 

 3. Method of Exercise. The option shall be exercised by written notice directed to the Compensation
Committee (the “Committee”), at the Corporation’s principal executive office, accompanied by payment of the option price for the number of Option Shares purchased in accordance with the Plan’s requirements. The Corporation shall
make delivery of such shares in accordance with the Plan provided that if any law or regulation requires the Corporation to take any action with respect to the shares specified in such notice before the issuance thereof, then the date of delivery of
such shares shall be extended for the period necessary to take such action. 
 4. The Plan. The Corporation’s 2002
Stock Incentive Plan, as amended from time to time by the Board of Directors of the Corporation, is hereby incorporated in this letter and to the extent that anything in this letter is inconsistent with the Plan, the terms of the Plan shall control.
Employee acknowledges that the Corporation has provided a copy of the Plan to Employee. The Optionee has received a copy of the Prospectus covering the Option Shares. 
 5. Termination of Option. Except as herein otherwise stated, the option, to the extent not previously exercised, shall terminate in accordance with the Plan and upon the first to occur of the
following events: 
 (a) Disability. The expiration of 36 months after the date on which Employee’s employment by
the Corporation is terminated, if such termination be by reason of Employee’s permanent and total Disability (as defined by the Corporation’s Compensation Committee), provided, however, that (i) the option shall be exercisable only to
the extent that Employee had the right to exercise the option at the time of 

 
termination, and (ii) if the Employee dies within such 36 month period, any unexercised option held by such Employee shall thereafter be exercisable in accordance with the provisions of and
shall terminate upon the first to occur of the events described in Sections 5(b) and (d); 
 (b) Death. In the event of
Employee’s death while in the employ of the Corporation, the expiration of 12 months following the date of death, provided that the option shall be exercisable following the Employee’s death only to the extent that Employee had the right
to exercise the option at the time of his or her death. 
 (c) Retirement. In the event Employee’s employment with
the Corporation terminates by reason of normal or early Retirement (as defined by the Corporation’s Compensation Committee), any option held by such Employee may be exercised by the Employee for a period of 36 months from the date of such
termination, provided, however, that (i) the option shall be exercisable only to the extent that Employee had the right to exercise the option at the time of termination, and (ii) if the Employee dies within such 36 month period any
unexercised option held by Employee shall thereafter be exercisable in accordance with the provisions of and shall terminate upon the first to occur of the events described in Section 5(b) and (d); or 

(d) Other. Upon the earlier to occur of (i) 84 months following the Grant Date, or (ii) upon termination of
Employee’s employment by the Corporation (except if such termination be by reason of death, disability, or normal or early Retirement). 
 Except as set forth above, the option may not be exercised unless Employee, at the time he/she exercises the option, is, and has been at all times since the date of grant of the option, an employee of the
Corporation. Employee shall be deemed to be employed by the Corporation if he/she is employed by the Corporation or any of its subsidiaries. Notwithstanding the above, in no event may the option be exercised after 84 months following the Grant Date.

 6. Reclassification, Consolidation, or Merger. The number of Option Shares may be adjusted in accordance with the Plan
if certain events such as merger, reorganization, consolidation, recapitalization, stock dividends, stock splits, or other changes in the Corporation’s corporate structure affecting its Common Stock occur. 

 7. Rights Prior to Exercise of Option. This Option is not transferable by Employee,
except by will or by the laws of descent and distribution or as otherwise set forth in the Plan, and during Employee’s lifetime shall be exercisable only by Employee. This option shall confer no rights to the holder hereof to act as stockholder
with respect to any of the Option Shares until payment of the option price and delivery of a share certificate has been made. 

8. Employee’s Representations and Warranties. By execution of this agreement, Employee represents and warrants to the
Corporation as follows: 
 (a). The entire legal and beneficial interest of the option and the Option Shares are for and will be
held for the account of the Employee only and neither in whole nor in part for any other person. 
 (b). Employee resides at the
following address: 

	
	
                __________________

	
                __________________

	
                __________________

(c). Employee is familiar with the Corporation and its plans, operations, and financial condition. Prior to the acceptance of this
option, Employee has received all information as he or she deems necessary and appropriate to enable an evaluation of the financial risk inherent in accepting the option and has received satisfactory and complete information concerning the business
and financial condition of the Corporation in response to all inquiries in respect thereof. 
 9. Restricted Securities.
Employee recognizes and understands that this option and the Option Shares are currently registered under the Securities Act of 1933, as amended (the “Act”), but may not remain so registered and are not registered under the Georgia Uniform
Securities Act of 2008, as amended (the “Georgia Act”), or any other state securities law. Any transfer of the option (if otherwise permitted hereunder, and once exercised, the Option Shares) will not be recognized by the Corporation
unless such transfer is registered under the Act, the Georgia Act, and any other applicable state securities laws or effected pursuant to an exemption from such registration which may then be available. If the Option Shares are not registered, any
share certificates representing the Option Shares may be stamped with legends restricting transfer thereof in accordance with the Corporation’s policy with respect to unregistered shares of its Common Stock issued to employees as a result of
exercise of options granted under the 

 
Plan. The Corporation may make a notation in its stock transfer records of the aforementioned restrictions on transfers and legends. Employee recognizes and understands that the Option Shares may
be restricted securities within the meaning of Rule 144 promulgated under the Act; that the exemption from registration under Rule 144 may not be available under certain circumstances and the Employee’s opportunity to utilize such Rule 144 to
sell the Option Shares may be limited or denied. The Corporation shall be under no obligation to maintain or promote a public trading market for the class of shares for which the option is granted or to make provision for adequate information
concerning the Corporation to be available to the public as contemplated under Rule 144. The Corporation will be under no obligation to recognize any transfer or sale of any Option Shares that are not registered under the Act unless the terms and
conditions of Rule 144 are complied with by the Employee. By acceptance hereof, Employee agrees that no permitted disposition of this option or any Option Shares shall be made unless and until (i) there is then in effect a registration
statement under the Act, the Georgia Act, and applicable state securities laws covering such proposed disposition and such disposition is made in accordance with such registration statement, or (ii) Employee shall have notified the Corporation
of a proposed option disposition and shall have furnished to the Corporation a detailed statement of the circumstances surrounding such disposition, and if requested by the Corporation, an opinion of counsel acceptable in form and substance to the
Corporation that such disposition will not require registration of the shares so disposed under the Act, the Georgia Act, and any applicable state securities laws. The Corporation shall be under no obligation to permit such transfer or disposition
on its stock transfer books unless counsel for the Corporation shall concur as to such matters. Employee recognizes and understands that as long as Employee remains a designated Section 16 officer of the Corporation, and for up to six months
thereafter, any sales of Option Shares will be subject to Section 16 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) and the regulations promulgated thereunder. Employee also recognizes and understands that any
sale of the Option Shares will also be subject to Rule 10b-5 promulgated under the Exchange Act. Employee agrees that any disposition of the Option Shares shall be made only in compliance with the Act, the Exchange Act, and the rules and regulations
promulgated thereunder. 
 10. Tax Matters. The Employee hereby agrees to comply with any applicable federal, state, and
local income and employment tax requirements which might arise with regard to a disposition of any Option Shares. No later than the date as of which an amount first becomes includable in the gross income of the Employee for federal income tax
purposes with respect to the exercise of any option 

 
under the Plan, Employee shall pay to the Corporation, or make arrangements satisfactory to the Committee regarding the payment of, any federal, state, or local taxes of any kind required by law
to be withheld with respect to such amount. The obligations of the Corporation under the Plan are conditional on such payment or arrangements and the Corporation shall have the right to deduct any such taxes from any payment of any kind otherwise
due to Employee. 
 11. Payment. The Option Exercise Price shall be paid in cash in U.S. Dollars at the time the Option
is exercised or in shares of Common Stock of the Corporation held by the employee for at least six months and having an aggregate value equal to the Option Exercise Price. If the Option Exercise Price is paid by transfer of shares of Common Stock of
the Corporation then the value of such shares will be determined by the last closing price of the Corporation’s Common Stock on the New York Stock Exchange prior to the exercise of the options. The Option Exercise Price may be paid by a
combination of cash and Common Stock. Notwithstanding the foregoing, subject to the prior approval of the Compensation Committee, Employee may elect to pay the Option Exercise Price by authorizing a third party to sell shares of stock (or a
sufficient portion of the shares) acquired upon exercise of the Option and remit to the Corporation a sufficient portion of the sale proceeds to pay the entire Option Exercise Price and any tax withholding resulting from such exercise. 

12. Binding Effect. This Agreement shall inure to the benefit of and be binding upon the parties hereto and their respective
heirs, executors, administrators, successors, and permissible assigns. 
 13. Miscellaneous. This Agreement shall be
governed by and construed under the laws of the State of Georgia. If any term or provision hereof shall be held invalid or unenforceable, the remaining terms and provisions hereof shall continue in full force and effect. Any modification to this
Agreement shall not be effective unless the same shall be in writing and such writing shall be signed by authorized representatives of both of the parties hereto. The terms of paragraphs 8 and 9 hereof shall survive exercise of the option by
Employee and shall attach to the Option Shares. The option contained in this letter shall not confer upon Employee any right to continued employment with the Corporation, nor shall it interfere in any way with the right of the Corporation to
terminate the employment of Employee at any time. This letter can be executed in two or more counterparts, each of which shall be deemed an original and all of which together shall constitute but one and the same instrument. 

 Please signify your acceptance of the option and your agreement to be bound by the terms
hereof by promptly signing one of the two original letters provided to you and returning the same to the Secretary of the Corporation. 
 Thank you for your good work and service. 
  

					
	  	  	 	  	THE CORPORATION:
			
	 (SEAL)
	  		  	
			
		  		  	CRYOLIFE, INC.
			
		  		  	  

		  		  	BY:
		  		  	TITLE:
			
	ATTEST:	  		  	
			
	  
	  		  	
	 BY:
	  		  	
	TITLE:	  		  	
			
	OPTIONEE:	  		  	
			
	  
	  		  	
	Name:

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