First Amendment to License, Supply and Distribution Agreement



 Exhibit 10.49 
 Confidential Materials omitted and filed separately with the 
 Securities and Exchange Commission. Asterisks
denote omissions. 
 FIRST AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT 
 THIS FIRST AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT is made and entered into as of this 19th day of December, 2005 (“Effective Date”) by and
between F.Hoffmann-La Roche Ltd. (“FHLR”) having a principal office at Grenzacherstrasse 124, Basel, Switzerland and 454 Life Sciences Corporation (“454”) having a principal office at 20 Commercial Street, Branford, CT 06405,
USA. 
 RECITALS 
 WHEREAS, the
Parties have entered into a written License, Supply and Distribution Agreement dated May 11, 2005 (“Original Agreement”); and 
 WHEREAS, according to the last paragraph of Section 2.7 of the Original Agreement the Parties wish to change the Initial estimated ASP in Section 3.3 (b) and Exhibit 2 of the Original Agreement and the Licensed
Products Specifications in Exhibit 3 of the Original Agreement. 
 NOW THEREFORE, in consideration of the covenants and mutual promises set forth
herein, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows: 
 1. According to Section 3.3 (b) of
the Original Agreement the Parties hereby define in detail the Licensed Products, the initial estimated ASP for the Licensed Products and the launch date by amending Exhibit 2. Exhibit 2 shall be replaced by the following new Exhibit 2:

 (See attached document.) 
 Furthermore, the launch date for
all Licensed Products shall be September 30, 2005. 
 2. Exhibit 3 of the Original Agreement shall be deleted in its entirety and replaced by the
following new Exhibit 3: 
 (See attached document.) 
 3.
The Parties agree that the “Accessories” listed on the new Exhibit 2 shall be treated the same as the Instrument regarding the payment of royalties. 
 4. According to Section 3.3 (c) the Parties have to agree on the applicable estimated ASP
for the following calendar year latest by November 30th. In deviation from this Section 3.3 (c) the
Parties agree that for the calendar year 2006 the applicable estimated ASP shall be as set out in Section 1 of this First Amendment. 
 IN
WITNESS WHEREOF, each of the Parties has caused this First Amendment to the Original Agreement to be executed by its duly authorized representative. 








									
	Basel,
F. Hoffmann-La Roche Ltd	 		 	Branford,
454 Life Sciences
					
	By:	 	/s/ Severin Schwan	 		 	By:	 	/s/ Christopher K. McLeod
	Name: 	 	Severin Schwan	 		 	Name: 	 	Christopher K. McLeod
	Title:	 	CEO Division Diagnostics	 		 	Title:	 	President & CEO
	Date:	 	Feb. 6, 2006	 		 	Date:	 	Jan. 9, 2006
				
	By:	 	/s/ C. J. Ruetsch	 		 	
	Name: 	 	C. J. Ruetsch	 		 		 	
	Title:	 	Legal Counsel	 		 		 	
	Date:	 	Feb. 2, 2006	 		 		 	









									
	Reagents
					
	 	  	Cat. No.	  	 Product
	  	 ASP
$/Kit
	  	 Transfer Price
$/Sub Kit

	 Kit
	  	04746694001	  	 GS 20 DNA Library Preparation Kit
	  	[**]	  	[**]
					
	 Sub Kit 1
	  	04746708001	  	 GS 20 DNA Library Preparation Kit Buffers
	  		  	[**]
					
	 Sub Kit 1
	  	04746716001	  	 GS 20 DNA Library Preparation Kit Enzymes and Adaptors
	  		  	[**]
					
	 Sub Kit 1
	  	04746724001	  	 GS 20 DNA Library Preparation Kit Nebulizers
	  		  	[**]
					
	 Sub Kit 1
	  	04746732001	  	 GS 20 DNA Library Preparation Kit Immobilization Beads
	  		  	[**]
					
	 Kit
	  	04746503001	  	 GS 20 emPCR Kit
	  	[**]	  	[**]
					
	 Sub Kit 1
	  	04746511001	  	 GS 20 emPCR Kit Bead Recovery Reagents
	  		  	[**]
					
	 Sub Kit 2
	  	04746520001	  	 GS 20 emPCR Kit Clonal Amplification Reagents
	  		  	[**]
					
	 Sub Kit 3
	  	04746538001	  	 GS20 emPCR Kit Enrichment Beads
	  		  	[**]
					
	 Sub Kit 4
	  	04746546001	  	 GS 20 emPCR Kit Emulsion Oil
	  		  	[**]
					
	 Kit
	  	04746554001	  	 GS 20 Sequencing Kit (70 x75)
	  	[**]	  	[**]
					
	 Sub Kit 1
	  	04746562001	  	 GS 20 Sequencing Kit (70x75) Pre-wash / Post-wash Buffers
	  		  	[**]
					
	 Sub Kit 2
	  	04746589001	  	 GS 20 Pre-wash Tubes
	  		  	[**]
					
	 Sub Kit 3
	  	04746597001	  	 GS 20 Sequencing Kit (70 x75) Wash Buffers
	  		  	[**]
					
	 Sub Kit 4
	  	04746619001	  	 GS 20 Sequencing Kit (70 x75) Sequencing Reagents
	  		  	[**]
					
	 Sub Kit 5
	  	04746627001	  	 GS 20 Sequencing Kit (70 x75) Sequencing Enzymes
	  		  	[**]
					
	 Sub Kit 6
	  	04746635001	  	 GS 20 Sipper Tubes
	  		  	[**]









									
	 Kit
	  	04746422001	  	 GS 20 Sequencing Kit (40x75)
	  	[**]	  	[**]
					
	 Sub Kit 1
	  	04746457001	  	 GS 20 Sequencing Kit (40x75) Pre-wash / Post-wash Buffers
	  		  	[**]
					
	 Sub Kit 2
	  	04746589001	  	 GS 20 Pre-wash Tubes
	  		  	[**]
		  		  		  		  	 
					
	 Sub Kit 3
	  	04746473001	  	 GS 20 Sequencing Kit (40x75) Wash Buffers
	  		  	[**]
					
	 Sub Kit 4
	  	04746481001	  	 GS 20 Sequencing Kit (40x75) Sequencing Reagents
	  		  	[**]
					
	 Sub Kit 5
	  	04746490001	  	 GS 20 Sequencing Kit (40x75) Sequencing Enzymes
	  		  	[**]
					
	 Sub Kit 6
	  	04746635001	  	 GS 20 Sipper Tubes
	  		  	[**]
		  		  		  		  	 
					
	 Kit
	  	04746759001	  	 GS 20 Maintenance Wash Kit
	  	[**]	  	[**]
					
	 Sub Kit 1
	  	04746767001	  	 GS20 Maintenance Wash Kit Maintenance Wash Reagents
	  		  	[**]
					
	 Sub Kit 2
	  	04746783001	  	 GS 20 Maintenance Wash Kit Bottles
	  		  	[**]
					
	 Sub Kit 3
	  	04746635001	  	 GS 20 Sipper Tubes
	  		  	[**]
		  		  		  		  	 
					
	 Kit
	  	04774981001	  	 GS 20 Installation Kit
	  	[**]	  	[**]
					
	 Sub Kit 1
	  	04774990001	  	 GS 20 Installation Kit Control DNA Beads
	  		  	[**]
					
	 Sub Kit 2
	  	04746457001	  	 GS 20 Sequencing Kit (40x75) Pre-wash / Post-wash Buffers
	  		  	[**]
		  		  		  		  	 
					
	 Sub Kit 3
	  	04746589001	  	 GS 20 Pre-wash Tubes
	  		  	[**]
		  		  		  		  	 









									
	Disposables
					
	 	  	Cat. No.	  	 Product
	  	 ASP
$/Kit
	  	 Transfer Price
$/Sub Kit

	 Kit
	  	04746821001	  	 GS 20 PicoTiterPlate Kit (70x75)
	  	[**]	  	[**]
					
	 Kit
	  	04746813001	  	 GS 20 PicoTiterPlate Kit (40x75)
	  	[**]	  	[**]









							
	Accessories
				
	Cat. No.	  	 Product
	  	 ASP
$/Kit
	  	 Transfer Price
$/ Kit

	04777034001	  	 Medium Bead Deposition Device, complete
	  	[**]	  	[**]
				
	04777042001	  	 Medium Bead Deposition Device, complete 8 lanes
	  	[**]	  	[**]
				
	04777069001	  	 Large Bead Deposition Device, complete
	  	[**]	  	[**]
				
	04777115001	  	 Counterweight for the Bead Deposition Devices
	  	[**]	  	[**]
				
	04777018001	  	 Camera Faceplate Guard
	  	[**]	  	[**]
				
	04777026001	  	 Nebulizer Holder
	  	[**]	  	[**]









									
	Instrument
	 Cat. No.
	  	 Product
	  	ASP
$	  	Transfer
Price $	  	Transfer Price
(incl Training Kits + Installation Kits) $
	 04746694001
	  	GS 20 DNA Instrument	  	[**]	  	[**]	  	[**]
		  	 including:
	  		  		  	
	 04777034001
	  	 Medium Bead Deposition Device, complete
	  		  		  	
	 04777042001
	  	 Medium Bead Deposition Device, complete 8 lanes
	  		  		  	
	 04777069001
	  	 Large Bead Deposition Device, complete
	  		  		  	
	 04777115001
	  	 Counterweight for the Bead Deposition Devices
	  		  		  	
	 04777018001
	  	 Camera Faceplate Guard
	  		  		  	
	 04777026001
	  	 Nebulizer Holder
	  		  		  	
		  	 Medium PicoTiterPlate Cartridge; 40x75
	  		  		  	
		  	 Large PicoTiterPlate Cartridge; 70x75
	  		  		  	
		  	 Swinlock Filter Unit
	  		  		  	
		  	 5 x 16 Gauge Blunt Needles
	  		  		  	
		  	 5 x Plastic Economy Foreceps
	  		  		  	
		  	 Zeiss Tissue (Box)
	  		  		  	
		  	 Wash Tube Holder
	  		  		  	
		  	 Extra Fluidics Waste Tank and Bottle Support
	  		  		  	
		  	 GS 20 DNA Library Preparation Kit User’s Manual
	  		  		  	
		  	 GS 20 DNA Library Preparation Kit Quick Guide
	  		  		  	
		  	 GS 20 emPCR Kit User’s Manual
	  		  		  	
		  	 GS 20 emPCR Kit Quick Guide
	  		  		  	
		  	 Genome Sequencer 20 Operator’s Manual
	  		  		  	
		  	 Genome Sequencer 20 Quick Guide
	  		  		  	
		  	 GS 20 Data Processing Software Manual
	  		  		  	
		  	 Genome Sequencer 20 Site Preparation Guide
	  		  		  	
					
		  	Additional items which must be ordered seperately	  		  		  	
					
		  	Training	  		  		  	
					
	 04746694001
	  	 GS 20 DNA Library Preparation Kit
	  		  	[**]	  	[**]
		  		  		  		  	 
	 04746503001
	  	 GS 20 emPCR Kit (3)
	  		  	[**]	  	[**]
					
	 04746554001
	  	 GS 20 Sequencing Kit (70x75)
	  		  	[**]	  	[**]
		  		  		  		  	 
	 04746422001
	  	 GS 20 Sequencing Kit (40x75) (3)
	  		  	[**]	  	[**]
					
	 04746821001
	  	 GS 20 PicoTiterPlate Kit (70x75)
	  		  	[**]	  	[**]
					
	 04746813001
	  	 GS 20 PicoTiterPlate Kit (40x75) (3)
	  		  	[**]	  	[**]
					
		  	 Installation
	  		  		  	
					
	 04774981001
	  	 GS 20 Installation Kit
	  		  	[**]	  	[**]
					
	 04746554001
	  	 GS 20 Sequencing Kit (70x75)
	  		  	[**]	  	[**]
					
	 04746821001
	  	 GS 20 PicoTiterPlate Kit (70x75)
	  		  	[**]	  	[**]








 Exhibit 3 
 Licensed Products Specifications 
 The following Specifications V 1.01 do not include the additional terms
that are laid down in the Original Agreement: 
  

	 	•	 	 update shelf life time of reagents up to [**] after Launch 


  

	 	•	 	 update of maintenance interval for tubings to [**] (not feasible for Version 1.01) 


  

							
	 NO
	  	Document ID	  	 Document Name
	  	PDF file
	 1
	  	SPC-00028	  	 454 Genome Sequencer Version 1.01 System Specifications
	  	[**]
	 2
	  	SPC-00034	  	 Instrument: Technical Requirements Specifications
	  	[**]
	 3
	  	SPC-00036	  	 Software: Software Requirement Specifications
	  	[**]
	 4
	  	SPC-00031	  	 Specifications Library Preparation Kit
	  	[**]
	 5
	  	SPC-00029	  	 Specification Emulsion-based Clonal Amplification Kit
	  	[**]
	 6
	  	SPC-00032	  	 Specification Sequencing Kit
	  	[**]
	 7
	  	SPC-00033	  	 Specifications PicoTiterPlate Kits
	  	[**]