Document:

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
	  	[**]Second Amendment to License, Supply and Distribution Agreement

 Exhibit 10.50 
 Confidential Materials omitted and filed separately with the 
 Securities and Exchange Commission. Asterisks
denote omissions. 
 SECOND AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT 
 THIS SECOND AMENDMENT TO LICENSE, SUPPLY AND DISTRIBUTION AGREEMENT is made and entered into as of this 24th day of October, 2006 (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, as amended by the First Amendment to License, Supply and Distribution Agreement dated December 19, 2005 (“Original Agreement”); and

 WHEREAS, the Parties intend to launch Rev. 1.1 (under the product name GS FLX) now a Proposed Licensed Product listed under Exhibit 5 of the
Original Agreement. Customers who bought the Rev. 1.0 (the product name being GS 20) will have the choice to upgrade their Rev 1.0 instrument to a Rev. 1.1 instrument. Hereby, the Parties wish to agree on the sharing of costs for such an upgrade.

 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. The following new Section 3.3 (e) shall be added to the Original Agreement: 
 “454 shall charge FHLR, and FHLR will purchase from 454 an upgrade for the Rev. 1.0 (“Upgrade”) at a transfer price of [**] percent ([**] %) for each of
the Upgrades based on the estimated Average Unit Upgrade Price (“AUUP”). The AUUP shall be the total amount invoiced to customers for Upgrades divided by the total number of Upgrades. The initial estimated AUUP for the
Upgrade shall be [**] US Dollars (US $ [**]). The value of the estimated AUUP shall be subject to adjustment based on the actual AUUP. The calculation of the actual AUUP shall be done in the same way as for the ASP in Section 3.3
(c) of the Original Agreement. 
 Furthermore, FHLR will pay 454 a fixed amount of [**] percent ([**] %) of the material costs for every upgrade of a
Rev. 1.0 which consists of the delivery according to Specifications of a Rev. 1.1 instrument [**]. The material costs for an Upgrade are currently [**] US Dollars (US $ [**]). In the event 454 does the Upgrade, FHLR shall also reimburse 454’s
actual costs for (i) travel of 454 personnel to upgrade Rev. 1.0 instruments (ii) personnel costs for the installation in the amount of $[**] per day of installation. These costs are the total costs of 454 for upgrading a Rev. 1.0 to a
Rev. 1.1 at the customer’s site. If FHLR does the Upgrade with its own technical service personnel, FHLR shall not be obligated to pay 454 costs for travel and installation. 
 Based on its 2006 forecast, FHLR has so far failed to order [**] Rev. 1.0 instruments from 454. Instead of purchasing those remaining Rev. 1.0 instruments, FHLR shall have the option to pay 454 a compensation of [**]
US Dollars (US $ [**]) per Rev. 1.0 instrument by December 31, 

 
2006. This shall be 454’s sole remedy for FHLR not taking delivery of the instruments. FHLR will inform 454 the latest by October 31, 2006 about
the number of Rev 1.0 instruments (if any) which it will order before December 31, 2006, with any unordered balance of the 2006 forecast subject to the above payment. 
 If FHLR has by the end of the calendar year 2006 any Rev. 1.0 instruments in stock and FHLR chooses to upgrade those instruments, FHLR shall only pay the material costs of [**] US Dollars (US $ [**]) for such Upgrade
without further payments. Such payment will not be deducted from any customer receipts for calculation of the ASP (Section 3.3) or royalties (Section 3.4) for the Rev. 1.1 instrument.” 
 2. The following new Section 3.4 (a)(vii) shall be added to the Original Agreement: 
 “[**] percent ([**] %) on Net Sales of Upgrades.” 
 3. The Upgrade will be done on the basis of the
following specifications (Exhibit 16): 
 (See attached document.) 
 4. Exhibit 3 shall be complemented according to Section 2.7 of the Original Agreement by addition of the Specifications for the Rev. 1.1 instrument as follows: 
 [**] 
 5. According to Section 3.3 (b) of the Original Agreement the Parties hereby amend Exhibit 2 by
adding the following for the additional Licensed Products Rev. 1.1, emPCR Kits II, III and paired end adaptor kit: 
 (See attached documents.) 

6. The Parties agree to amend the Original Agreement such that the text of Exhibit 5, “Proposed Licensed Products, Launch Dates and Initial Estimated
ASP” shall be deleted in its entirety and replaced with the following: 
 (See attached document.) 
 7. Both new GS FLX instruments and upgraded Rev. 1.0 (GS20) instruments are warranted by 454 to FHLR for [**] starting with installation of the GS FLX instruments
at the customer and with completion and installation at the customer of the upgrade for the Rev. 1.0 (GS20) instruments. This warranty is extended by FHLR or its Affiliates to the customer. 

 IN WITNESS WHEREOF, each of the Parties has caused this Second Amendment to the Original Agreement to be executed
by its duly authorized representative. 
  

									
	Basel,	 		 	Branford,
	F. Hoffmann-La Roche Ltd	 		 	454 Life Sciences
					
	By:	 	/s/ P. Saladin	 		 	By:	 	/s/ Christopher K. McLeod
	Name:	 	P. Saladin	 		 	Name:	 	Christopher K. McLeod
	Title:	 	Head of Diag. Licensing	 		 	Title:	 	President & CEO
	Date:	 	11/21/2006	 		 	Date:	 	Nov. 28, 2006

  

									
		 		 	
					
	By:	 	/s/ C. J. Ruetsch	 		 		 	
	Name:	 	Dr. C. J. Ruetsch	 		 		 	
	Title:	 	Head of Legal Diagnostics	 		 		 	
	Date:	 	November 21, 2006	 		 		 	

 The GS-20 to GS-100 upgrade 
 Manufacturing an Upgrade Performance overview 
 454 will produce 2 identical types of GS-100 instruments, whereas the instruments dedicated
for upgrades [**]. During the upgrade at the customer site the [**] of the GS-20 instrument already owned by the customer will be switched to the GS-100. 
 The upgrade at the customer site will take [**] days. The upgrade will be performed preferentially by trained* Roche service engineers. Where necessary Roche and 454 agree that Roche could contract the 454 engineer to perform the upgrade.
Approximately [**] hours will be needed to switch the [**] and to install/QC the upgraded instrument. Test fragment run will be performed [**], followed by data analysis, filling the installation form and packing the old GS-20 instrument. The
customer confirms the successful installation by signing the installation report. 
 Supply Chain Logistics Overview 
 The upgrade process follows already established supply chain mechanisms already in place for the GS-20. This is valid for entering the Purchase Order (PO_ as well as for
shipping of instrument and reagents to the customer. 
 In detail: 
 What parts will be sent to a customer upon ordering an upgrade? 
  

	 	•	 	 [**] 

 What has to happen to send the new
instrument ? 
  

	 	•	 	 [**] 

 What happens at the customer site
(Instrument, engineering)? 
  

	 	•	 	 [**] 

 Training concept 
  

	 	•	 	 Instrument: [**] 

  

	 	•	 	 Kits & Protocols: [**] 

 How it
will be confirmed that the upgrade has been successful? 
 [**] 
 Warranty 
  

	 	•	 	 Both, GS-100 system and [**] are warranteed by 454 to Roche for [**]. This warranty is extended by Roche to the customer 

  

	*	Training of Roche staff by 454 

 1. Service engineers

 454 ([**]) will provide a common training for 2-3 service engineers from Roche Global System Support (GSS) and 2-3 service engineers from Roche U.S.
Technical Services. Training will take place at 454 as soon as a GS-100 instrument will be available (GS-20 instrument in the 454 Sequencing Centre owned by Roche U.S. will be used to train the [**] switch). Training contains entire procedure
(hands-on) of all steps done by the service engineers during the upgrade. 
 2. Roche training staff 
 Roche Global Customer Support (one person) will need one week training at 454 in October to update the training guide and to become familiar with the instrument. This
person will then train rest of Roche staff. Training needs for the U.S. colleagues will be similar. 
 To be organized by [**]. 

									
	Kit	  	04891384001	  	GS emPCR Kit II (Amplicon A, Paired End)	  	[**]	  	[**]
					
	Sub Kit 1	  	04891406001	  	GS emPCR Kit II (Amplicon A, Paired End) Bead Recovery Reagents	  		  	[**]
					
	Sub Kit 2	  	04891414001	  	GS emPCR Kit II (Amplicon A, Paired End) Clonal Amplification Reagents	  		  	[**]
					
	Sub Kit 3	  	04746538001	  	GS emPCR Kit Enrichment Beads	  		  	[**]
					
	Sub Kit 4	  	04746546001	  	GS emPCR Kit Emulsion Oil	  		  	[**]
					
	Kit	  	04891392001	  	GS 20 emPCR Kit III (Amplicon B)	  	[**]	  	[**]
					
	Sub Kit 1	  	04891422001	  	GS emPCR Kit III (Amplicon B) Bead Recovery Reagents	  		  	[**]
					
	Sub Kit 2	  	04891449001	  	GS emPCR Kit III (Amplicon B) Clonal Amplification Reagents	  		  	[**]
					
	Sub Kit 3	  	04746538001	  	GS emPCR Kit Enrichment Beads	  		  	[**]
					
	Sub Kit 4	  	04746546001	  	GS emPCR Kit Emulsion Oil	  		  	[**]
					
	Kit	  	04891457001	  	GS Paired End Adaptor Kit	  	[**]	  	[**]

							
	 GS FLX Product Line
	  	 Catalog No
	  	 Initial Average Selling Price
Per Kit
(USD)
	  	 Transfer Price

				
	 GS FLX LR20 Sequencing Kit
	  	04 852 419 001	  	[**]	  	[**]
				
	 PicoTiterPlate Kit (20 x 25)
	  	04 746 813 001	  	[**]	  	[**]
				
	 GS FLX LR70 Sequencing Kit
	  	04 853 342 001	  	[**]	  	[**]
				
	 GS FLX System
	  		  	[**]	  	[**]
				
	 GS20 Upgrade to GS FLX
	  		  	[**]	  	[**]

 EXHIBIT 5 
 Proposed Licensed Products, Launch Dates and Initial estimated ASP 
 Version 2.0

  

					
	 System Components
	  	Launch Date	  	 Initial Estimated
 ASP

	 Sequencer Instrument V 2.0
	  	2008	  	tbd
	 Software V 2.0
	  		  	
	 DNA Library Preparation Kit
	  		  	tbd
	 Emulsion-based Clonal Amplification Kit
	  		  	
	 PicoTiter Sequencing Kits
	  		  	
	 PicoTiterPlate Kits
	  		  	tbd

  

	Other	Components as well as details tbd at the Steering Committee

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