Document:

EX-4.2.1

 Exhibit 4.2.1 

AMENDMENT NO. 1 TO THE PATENT LICENSE AGREEMENT NO. C-00061906 

BETWEEN: 
 L’Institut Pasteur, 

Foundation recognized as having public utility, 
 25-28, rue du Docteur Roux, 
 75724 Paris cedex 15, 

represented by Mr. Christian POLICARD, 
 Director of
Development and Industrial Partnerships. 
 Hereafter referred as to as “IP” or the “LICENSOR”, 

Party of the first part 
 AND: 

CELLECTIS 
 Public limited company with capital with a
capital of 122,363.47 euros, 
 with its registered office at at 28, rue du Docteur Roux, 75724 Paris cedex 15, 

represented by Mr. André Choulika, acting in the capacity of CEO 

Hereafter referred to as “CELLECTIS” or the “LICENSEE”, 

Party of the second part. 
 The LICENSOR and the LICENSEE
are hereafter referred to as the “Parties”. 
 RECITALS: 

IP owns patents and patent applications relating to a method of homologous recombination. 

On June 19, 2000, the Parties signed licensing agreement no. C-00061906 (hereafter the “AGREEMENT”), by
which the LICENSOR grants the LICENSEE exploitation rights under the above mentioned patents and patent applications. 
 After discussions and exchanges
between the Parties, they have decided to modify the provisions of the AGREEMENT. 
 It is thus agreed as follows: 

ARTICLE 1 
 1.1 The Parties agree that the words
defined in Article 1, “DEFINITIONS”, of the AGREEMENT, as they are used in this amendment, have the same definitions as in the AGREEMENT and form an integral part of this amendment. 

1.2 The following definitions apply for the purposes of this amendment, it being understood when permitted by context that the singular shall be considered to
include the plural and vice versa: 

	 	1.2.1	 By “I-SceI and/or I-Spom I” the Parties agree to mean the technologies claimed by the
AGREEMENT PATENTS of LICENSE AGREEMENT no. C-00061901 signed between the Parties. 

  

	 	1.2.2	 By “PGN”, the Parties agree to mean the technologies claimed by the AGREEMENT PATENTS of LICENSE
AGREEMENT no. C-00061906 signed between the Parties. 

  

	 	1.2.3	 By “Mulligan”, the Parties agree to mean the technologies claimed by the AGREEMENT PATENTS of LICENSE
AGREEMENT no. C-00061905 signed between the Parties. 

  

	 	1.2.4	 For the sole purposes of articles 3.4 and 3.5 as modified by this amendment, the word “TOOL” will
have the definition stated below: 

 By “TOOL”, the Parties agree to mean the use by the LICENSEE’S SUB-LICENSEE of the LICENSED PROCESSES or LICENSED PRODUCTS for internal purposes or as part of the research or development process conducted by the sub-licensee. 

ARTICLE 2 
 Article 2.4 of the AGREEMENT is
modified by the following provisions, which supersede all previous provisions of that same article: 
  

	“2.4	 The LICENSEE may only grant sub-licenses to THIRD PARTIES for the
rights which it receives under this Agreement with the prior AGREEMENT of the LICENSOR. If the LICENSOR does not communicate its disagreement within twenty-one days from the notification of a sub-licensing project, it shall be considered to have agreed. 

 The LICENSOR may refuse
to grant prior agreement for a sub-license only for serious cause. 
 The following would constitute
serious cause justifying IP’s refusal to agree: a sub-licensing Amendment between the LICENSEE and a THIRD PARTY containing provisions which are contrary to the ethics, image or intellectual property of
the LICENSOR.” 
 ARTICLE 3 
 Article 3.4 of
the AGREEMENT is modified by the following provisions, which supersede all previous provisions of the same article: 
  

	“3.4.1	 For sub-licenses concerning a LICENSED PATENT for the use of TOOLS
granted by the LICENSEE under Article 2.4 of this AGREEMENT, the LICENSEE will pay the LICENSOR 40% of any compensation it receives, lump sums, royalties, market values (for cross-licensing or exchanges) for all
sub-licenses granted to THIRD PARTIES.” 

  

	3.4.2	 For sub-licenses concerning LICENSED PATENTS other than those mentioned
in Article 3.4.1 above, granted by the LICENSEE under Article 2.4 of this AGREEMENT, the LICENSEE will pay to the LICENSOR 40% of any compensation it receives, lump sums, royalties, market values (for cross-licensing or exchanges) for all sub-licenses granted to THIRD PARTIES, excluding the amounts stipulated in Article 3.5, without the amount of the royalties owed to the LICENSOR being less than: 

 • 2% of the net income of the sub-licensee for
the ISCEI and/or I-Spom I technologies, Mulligan and PGN granted together to the same sub-licensee; 

• 1% of the net income of the sub-licensee for ISCEI and/or I-Spom I technologies granted alone or
with Mulligan to the same sub-licensee. 
 ARTICLE 4 

The last sentence of article 10.1 par. 2 is modified as follows: 

“This share must not be less than 7,621 EUROS ex tax per year.” 

ARTICLE 5 
 Article 2.6 of the licensing AGREEMENT
is modified by the following provisions, which supersede all previous provisions of the same article: 
 “The IMPROVEMENTS achieved by the LICENSOR are
exclusively licensed to the LICENSEE for a period of 5 (five) years following the date of signature of Amendment no. 1 to this AGREEMENT. 
 “The
LICENSOR will inform the LICENSEE of the existence and contents of the IMPROVEMENTS. 
 “Following the 5 year period, the Parties will come together to
mutually agree on the terms of access to the IMPROVEMENTS.” 
 ARTICLE 6 

The last sentence of article 1.5 of the AGREEMENT is modified as follows: 

“Patents filed to protect IMPROVEMENTS will be included in the AGREEMENTS PATENTS under the AGREEMENT in accordance with the provisions of Article 2.6 of
this AGREEMENT.” 
 ARTICLE 7 
 This
amendment will enter into force on the date of its signature. 
 The other provisions of the AGREEMENT remain unchanged and in force between the Parties.

 Signed in Paris on                [Handwritten text: September 8,
2003] 
 in 2 original copies. 
  

			
	CELLECTIS	  	INSTITUT PASTEUREX-4.2.2

 Exhibit 4.2.2 

AMENDMENT NO. 2 TO THE PATENT LICENSE AGREEMENT NO. C-00061906 

BETWEEN: 
 L’Institut Pasteur, a public
interest foundation, 25, rue du Docteur Roux, 75015 Paris, represented by Mr. Jean Castex, adjunct General Manager for administration and finance, and by Mr. Christian POLICARD, Director of Business Development and Industrial Partnerships.

 Hereafter referred to as “IP” or the “LICENSOR”, 

Party of the first part, 
 AND: 

CELLECTIS, a public limited company with a capital of 122,363.47 euros, headquartered at 102, route de Noisy, 93235 Romainville cedex, represented by
Mr. André Choulika, acting as Chief Executive Officer 
 Hereafter referred to as “CELLECTIS” or the “LICENSEE”, 

Party of the second part. 
 The LICENSOR and LICENSEE are
hereafter referred to as the “Parties”. 
 RECITALS: 

IP owns patents and patent applications relating to a method of homologous recombination. 

On June 19, 2000, the Parties signed the license agreement no. C-00061906 (hereafter the “AGREEMENT”),
by which the LICENSOR grants the LICENSEE exploitation rights to the patents and patent applications mentioned above. 
 The Agreement was the subject of a
first amendment signed on September 8, 2003 and an email dated September 26, 2003 modifying the FIELD of the AGREEMENT. 
 After discussions and
exchanges between the Parties, they have decided to modify the provisions of the AGREEMENT. 
 It is thus agreed as follows: 

ARTICLE 1 
  

	1.1	 The Parties agree that the words defined in Article 1, “DEFINITIONS”, of the AGREEMENT, as they are
used in this amendment, have the same definitions as in the AGREEMENT and form an integral part of this amendment. 

  

	1.2	 The following definitions apply for the purposes of this amendment, it being understood when permitted by
context that the singular shall be considered to include the plural and vice versa: 

  

	 	1.2.1	 By “I-SceI and/or I-Spom I” the Parties agree to mean the technologies claimed by the
AGREEMENT PATENTS of LICENSE AGREEMENT no. C-00061901 signed between the Parties. 

	 	1.2.2	 By “PGN”, the Parties agree to mean the technologies claimed by the AGREEMENT PATENTS of LICENSE
AGREEMENT no. C-00061906 signed between the Parties. 

  

	 	1.2.3	 By “Mulligan”, the Parties agree to mean the technologies claimed by the AGREEMENT PATENTS of LICENSE
AGREEMENT no. C-00061905 signed between the Parties. 

 ARTICLE 2 

Article 1.3 of the AGREEMENT is modified by the following provisions, which supersede all previous provisions of the same article: 

1.3 FIELD 
 The FIELD of the
AGREEMENT covers the field of homologous recombination applied to all genes other than those of cytokines, hormones and human growth factors. 

This exclusion does not apply in either of the following cases: 
  

	 	(i)	 As part of the creation of test animals used as a research and medication screening and validation tool;

  

	 	(ii)	 As part of use combined with the PGN patents on the one hand and I-SceI and/or I-Spom I and/or Mulligan on the
other hand, excluding applications for Erythropoietin (EPO). 

 ARTICLE 3 

Under this Amendment, the LICENSEE will pay the LICENSOR on the date of signing of this amendment a fixed,
non-refundable and non-deductible payment of 50,000 EUROS ex tax. 

ARTICLE 4 
 This amendment will enter into force on
the date of its signature. 
 The AGREEMENT’s other provisions remain unchanged and in force between the Parties. 

Signed in Paris on [Handwritten text: June 24, 2004] 
 in 2
original copies. 
  

			
	CELLECTIS	  	INSTITUT PASTEUR

																	
								
		  		  		  		  		  		  		  	Received on July 2, 2004
							
	INSTITUT PASTEUR	  		  		  		  		  		  	Paris, July 1, 2004
					
	Technology Transfer Department	  		  	Mrs. Isabelle Pelletier-Bressag	  		  	
		  		  		  		  	Business Development	  		  	
		  		  		  		  	CELLECTIS SA	  		  	
		  		  		  		  	102 route de Noisy	  		  	
		  		  		  		  	93235 ROMAINVILLE CEDEX	  		  	
								
	Our ref.:	  	JPS-CPT/138-04	  		  		  		  		  		  	
	Your ref.:	  	BD_COU_040625_I	  		  		  		  		  		  	
						
	From:	  	Christine Phan	  	Telephone:	  	01.45.68.81.92	  		  	
		  		  		  	Fax:	  	01.40.61.37.32	  		  		  	
		  		  		  	Email:	  	cphan@pasteur.fr	  		  		  	

 Case handled by: Jean-Pierre Saintouil 

SUBJECT: Amendment no. 2 to patent licensing contract no. C-00061906 

 Dear Madam, 

Please find attached an original copy of Amendment no. 2 to Patent Licensing Contract no. C-00061906 signed by Messrs.
C. Policard and J. Castex. 
 Please accept our most distinguished regards. 

Christine Phan 
 Marketing Assistant

 Department of Business Development and Industrial Partnerships 

25-26 rue du Docteur Roux 

75724 Paris cedex 15 
 Telephone: +33 (0)1 45 68 81 06

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