Document:

First Amendment to Loan and Security Agreement

 Exhibit 10.56 
  
 FIRST AMENDMENT TO 
  
 LOAN AND SECURITY AGREEMENT 
  
 THIS FIRST AMENDMENT to Loan and Security Agreement (this “Amendment”) is entered into this 18th day of July, 2005, by and between Silicon Valley Bank (“Bank”) and Nuvelo, Inc., a Delaware corporation (“Borrower”) whose
address is 675 Almanor Avenue, Sunnyvale, California 94085. 
  
 RECITALS 
  
 A. Bank and
Borrower have entered into that certain Loan and Security Agreement dated as of August 30, 2004, (as the same may from time to time be further amended, modified, supplemented or restated, the “Loan Agreement”). 
  
 B. Bank has extended credit to Borrower for the purposes permitted in
the Loan Agreement. 
  
 C. Borrower has requested that Bank
amend the Loan Agreement to (i) increase the amount available to be borrowed under the Revolving Line and (ii) extend the maturity date. 
  
 D. Bank has agreed to so amend certain provisions of the Loan Agreement, but only to the extent, in accordance with the terms, subject to the
conditions and in reliance upon the representations and warranties set forth below. 
  
 AGREEMENT 
  
 NOW, THEREFORE, in consideration of the foregoing recitals and other good and valuable consideration, the receipt and adequacy of which is hereby acknowledged, and intending to be legally bound, the
parties hereto agree as follows: 
  
 1. Definitions.
Capitalized terms used but not defined in this Amendment shall have the meanings given to them in the Loan Agreement. 
  
 2. Amendments to Loan Agreement. 
  
 2.1 Section 2.1.1 (Revolving Advances). Sub letter (b) of Section 2.1.1 is hereby amended in part to provide that interest on each
Advance shall be paid on the 29th of each month. 
  
 2.2 Section 6.6 (Operating and Investment Accounts).
Notwithstanding anything to the contrary contained in Section 6.6, Borrower may maintain (a) its certificate of deposit with Union Bank of California in an amount not to exceed $191,000 until Borrower’s Letter of Credit with Union Bank of
California has expired and (b) an operating account at Union Bank of California to collect interest on such certificate of deposit, provided, however, at such time when the Letter of Credit has expired, Borrower shall transfer the funds evidenced by
the certificate of deposit to its accounts with or through Bank. 
  

 2.3 Section 13 (Definitions). The following terms and their respective definitions
set forth in Section 13.1 are amended in their entirety and replaced with the following; 
  
 “Committed Revolving Line” is an Advance or Advances in an aggregate amount of up to $8,000,000. 
  
 “Revolving Maturity Date” is August 29,
2006. 
  
 3. Limitation of Amendments. 
  
 3.1 The amendments set forth in Section 2,
above, are effective for the purposes set forth herein and shall be limited precisely as written and shall not be deemed to (a) be a consent to any amendment, waiver or modification of any other term or condition of any Loan Document, or (b)
otherwise prejudice any right or remedy which Bank may now have or may have in the future under or in connection with any Loan Document. 
  
 3.2 This Amendment shall be construed in connection with and as part of the Loan Documents and all terms, conditions,
representations, warranties, covenants and agreements set forth in the Loan Documents, except as herein amended, are hereby ratified and confirmed and shall remain in full force and effect. 
  
 4. Representations and Warranties. To induce Bank to enter into this
Amendment, Borrower hereby represents and warrants to Bank as follows: 
  
 4.1 Immediately after giving effect to this Amendment (a) the representations and warranties contained in the Loan Documents are true, accurate and complete in all material respects as of the date hereof
(except to the extent such representations and warranties relate to an earlier date, in which case they are true and correct as of such date), and (b) no Event of Default has occurred and is continuing; 
  
 4.2 Borrower has the power and authority to execute
and deliver this Amendment and to perform its obligations under the Loan Agreement, as amended by this Amendment; 
  
 4.3 The Articles of Incorporation and By-Laws of Borrower, as publicly available or provided to Bank, are in full force and effect
as of the date of this Amendment; 
  
 4.4
The execution and delivery by Borrower of this Amendment and the performance by Borrower of its obligations under the Loan Agreement, as amended by this Amendment, have been duly authorized; 
  
 4.5 The execution and delivery by Borrower of this
Amendment and the performance by Borrower of its obligations under the Loan Agreement, as amended by this Amendment, do not and will not contravene (a) any law or regulation binding on or affecting Borrower, (b) any contractual restriction with a
Person binding on Borrower, 

  

 
(c) any order, judgment or decree of any court or other governmental or public body or authority, or subdivision thereof, binding on Borrower, or (d) the
organizational documents of Borrower; 
  
 4.6 The execution and delivery by Borrower of this Amendment and the performance by Borrower of its obligations under the Loan Agreement, as amended by this Amendment, do not require any order, consent, approval, license,
authorization or validation of, or filing, recording or registration with, or exemption by any governmental or public body or authority, or subdivision thereof, binding on either Borrower, except as already has been obtained or made; and 

 
 4.7 This Amendment has been duly executed and
delivered by Borrower and Bank and is the binding obligation of Borrower and Bank, enforceable against Borrower and Bank in accordance with its terms, except as such enforceability may be limited by bankruptcy, insolvency, reorganization,
liquidation, moratorium or other similar laws of general application and equitable principles relating to or affecting creditors’ rights. 
  
 5. Counterparts. This Amendment may be executed in any number of counterparts and all of such counterparts taken together shall be deemed to
constitute one and the same instrument. 
  
 [Signature page
follows.] 
  

 IN WITNESS WHEREOF, the parties hereto
have caused this Amendment to be duly executed and delivered as of the date first written above. 
  

									
	BANK	 	 	 	BORROWER
			
	 Silicon Valley Bank
	 	 	 	 Nuvelo, Inc.

					
	 By: 
	 	 /s/ Liam Fairbairn
	 	 	 	 By: 
	 	 /s/ Lee Bendekgey

	 Name: 
	 	 Liam Fairbairn
	 	 	 	 Name: 
	 	 Lee Bendekgey

	 Title: 
	 	 Relationship Manager
	 	 	 	 Title: 
	 	 SVP, CFO & General CounselSupplemental Indenture between JPMorgan Chase & The Bank of New York

 Exhibit 4.2 
  

JPMORGAN CHASE & CO. 
  
 (Formerly Known As The Chase Manhattan Corporation) 
  
 AND 
  
 THE BANK OF NEW YORK, 
  
 as Trustee 
  
 SUPPLEMENTAL
INDENTURE 
  
 Dated as of September 23, 2004 
  
 to 
  
 JUNIOR SUBORDINATED INDENTURE 
  
 Dated as of December 1, 1996 

 SUPPLEMENTAL INDENTURE, dated as of September 23, 2004, between JPMORGAN CHASE & CO. (formerly known
as “The Chase Manhattan Corporation”), a Delaware corporation (the “Company”) having its principal office at 270 Park Avenue, New York, NY 10017, and THE BANK OF NEW YORK, a New York banking corporation, as Trustee (the
“Trustee”). 
  
 WITNESSETH: 
  
 WHEREAS, the Company and the Trustee have heretofore executed and delivered
a certain Junior Subordinated Indenture, dated as of December 1, 1996 (the “Indenture”; capitalized terms not otherwise defined herein shall have the meanings set forth in the Indenture), providing for the issuance from time to time of
Securities; 
  
 WHEREAS, Section 9.1 of the Indenture provides
that a supplemental indenture may be entered into by the Company and the Trustee without the consent of any Holder of any Securities to change or eliminate any of the provisions of the Indenture, provided that any such change or elimination shall
become effective only when there is no Security outstanding of any series created prior to the execution of such supplemental indenture which is entitled to the benefit of such provision; 
  
 WHEREAS, Section 9.1 of the Indenture provides that a supplemental indenture may be entered into by the Company and the
Trustee without the consent of any Holder of any Securities to establish the form or terms of Securities of any series as permitted by Sections 2.1 or 3.1 of the Indenture, and pursuant thereto the Company has determined to establish certain
provisions of the form and terms of Securities in each series issued on or after the date hereof; 
  
 WHEREAS, the conditions set forth in the Indenture for the execution and delivery of this Supplemental Indenture have been satisfied; and 
  
 WHEREAS, all things necessary to make this Supplemental Indenture a valid
agreement of the Company and the Trustee, in accordance with its terms, and a valid amendment of, and supplement to, the Indenture have been done. 
  
 NOW, THEREFORE, in consideration of the premises and the purchase of the Securities by the Holders thereof from time to time on or after the date hereof,
it is mutually covenanted and agreed, for the equal and proportionate benefit of all such Holders, that the Indenture is supplemented and amended, to the extent and for the purposes expressed herein, as follows: 
  
 ARTICLE I 
  
 SCOPE OF THIS SUPPLEMENTAL INDENTURE 
  

1.1. The changes, modifications and supplements to the Indenture effected by this Supplemental Indenture in Sections 2.1 through 2.6 hereof shall only
be applicable with respect to, and govern the terms of, any series of Securities issued on or after the date hereof, and shall not apply to any series of Securities which have been issued under the Indenture prior to such date. 

 ARTICLE II 
  
 AMENDMENTS 
  
 2.1. All references in the Indenture to the term “business trust” shall be deleted and the term “statutory trust” shall be inserted in
their place. 
  
 2.2. The definition of “Debt” contained
in Section 1.1 of the Indenture is hereby amended in its entirety to read as follows: 
  
 “Debt” means, with respect to any Person, whether or not contingent, (i) every obligation of such Person for the repayment of
money borrowed whether or not evidenced by bonds, debentures, notes or other written instruments, and any deferred obligation for payment of the purchase price of property or assets; (ii) every obligation of such Person for claims in respect of
derivative products, including interest rate, foreign exchange rate and commodity forward contracts, options and swaps and similar arrangements; and (iii) every obligation of the type referred to in clauses (i) and (ii) of another Person the payment
of which, in either case, such Person has guaranteed or is responsible or liable for, directly or indirectly, as obligor or otherwise. 
  
 2.3. The definition of “Senior Debt” contained in Section 1.1 of the Indenture is hereby amended in its entirety to read as follows: 

 
 “Senior Debt” means the principal of (and
premium, if any) and interest, if any (including interest accruing on or after the filing of any petition in bankruptcy or for reorganization relating to the Company whether or not such claim for post-petition interest is allowed in such proceeding)
on Debt of the Company, whether incurred on or prior to the date of this Indenture or thereafter incurred, unless, in the instrument creating or evidencing the same or pursuant to which the same is outstanding, it is provided that such obligations
are not superior in right of payment to the Securities or to other Debt which is pari passu with, or subordinated to, the Securities; provided, however, that Senior Debt shall not be deemed to include any Securities or other junior subordinated debt
obligations of the Company issued in respect of capital securities (and the related common securities) issued by trusts organized by the Company and treated as capital of the Company for bank regulatory purposes. 
  
 2.4. Section 2.3 of the Indenture is hereby amended by deleting the eighth
and ninths paragraphs of such Section and inserting the following in its place: 
  
 [If the Security is not a Discount Security, -As provided in and subject to the provisions of the Indenture, if an Event of Default
arising from a default in the payment of interest as set forth in Section 5.1(6) of the Indenture with respect to the Securities of this series at the time Outstanding occurs and is continuing, then and in every such case the Trustee or the Holders
of not less than 25% in principal amount of the Outstanding Securities of this series may declare the principal amount of all the Securities of this series to be due and payable immediately, by a notice in writing to the Company (and to the Trustee
if given by Holders), provided that, in the case of the 

  

 2 

 
Securities of this series issued to a Trust, if upon such an Event of Default, the Trustee or the Holders of not less than 25% in principal amount of the
Outstanding Securities of this series fail to declare the principal of all the Securities of this series to be immediately due and payable, the holders of at least 25% in aggregate Liquidation Amount of the Preferred Securities then outstanding
shall have such right by a notice in writing to the Company and the Trustee; and upon any such declaration the principal amount of and the accrued interest (including any Additional Interest) on all the Securities of this series shall become
immediately due and payable, provided that the payment of principal and interest (including any Additional Interest) on such Securities shall remain subordinated to the extent provided in Article XIII of the Indenture. As provided in and subject to
the provisions of the Indenture, if an Event of Default arising from events of bankruptcy, insolvency or reorganization involving the Company as set forth in Section 5.1(4) or 5.1(5) of the Indenture with respect to the Securities of this series at
the time Outstanding occurs and is continuing, then and in every such case the principal amount of and the accrued interest (including any Additional Interest) on all the Securities of this series shall automatically, and without any declaration or
other action on the part of the Trustee or any Holder, become immediately due and payable, provided that the payment of principal and interest (including any Additional Interest) on such Securities shall remain subordinated to the extent provided in
Article XIII of the Indenture.] 
  
 [If the
Security is a Discount Security,-As provided in and subject to the provisions of the Indenture, if an Event of Default arising from a default in the payment of interest as set forth in Section 5.1(6) of the Indenture with respect to the
Securities of this series at the time Outstanding occurs and is continuing, then and in every such case the Trustee or the Holders of not less than such portion of the principal amount as may be specified in the terms of this series may declare an
amount of principal of the Securities of this series to be due and payable immediately, by a notice in writing to the Company (and to the Trustee if given by Holders), provided that, in the case of the Securities of this series issued to a Trust, if
upon such an Event of Default, the Trustee or the Holders of not less than such specified principal amount of the Outstanding Securities of this series fail to declare the principal of all the Securities of this series to be immediately due and
payable, the holders of at least 25% in aggregate Liquidation Amount of the Preferred Securities then outstanding shall have such right by a notice in writing to the Company and the Trustee. As provided in and subject to the provisions of the
Indenture, if an Event of Default arising from events of bankruptcy, insolvency or reorganization involving the Company as set forth in Section 5.1(4) or 5.1(5) of the Indenture with respect to the Securities of this series at the time Outstanding
occurs and is continuing, then and in every such case an amount of principal of the Securities of this series shall automatically, and without any declaration or other action on the part of the Trustee or any Holder, become immediately due and
payable. In either case, such amount shall be equal to [– insert formula for determining the amount]. Upon any such declaration or automatic acceleration, such amount of the principal of and the accrued interest (including any Additional
Interest) on all the Securities of this series shall become immediately due and payable, provided that the payment of principal and interest (including any Additional Interest) on such Securities shall remain subordinated to the extent provided in
Article XIII of the Indenture.] 
  

 3 

 2.5. Section 5.1 of the Indenture is hereby amended by renumbering existing clause (6) as clause (7) and
inserting the following clause after clause (5): 
  
 (6) default in the payment of interest in full upon any Security of that series for a period of 30 days after the conclusion of a period consisting of 20 consecutive quarters (or, in the case of any Security on which interest is paid
semiannually, 10 consecutive semiannual periods) commencing with the earliest quarter or semiannual period, as the case may be, for which interest (including interest accrued on deferred payments) has not been paid in full; or 
  
 2.6. Section 5.2 of the Indenture is hereby amended by deleting the first
paragraph of such Section and inserting the following in its place: 
  
 If an Event of Default specified in Section 5.1(6) with respect to Securities of any series at the time Outstanding occurs and is continuing, then and in every such case the Trustee or the Holders of not less than 25%
in principal amount of the Outstanding Securities of that series may declare the principal amount (or, if the Securities of that series are Discount Securities, such portion of the principal amount as may be specified in the terms of that series) of
all the Securities of that series to be due and payable immediately, by a notice in writing to the Company (and to the Trustee if given by Holders), provided that, in the case of the Securities of a series issued to a Trust, if, upon such an Event
of Default, the Trustee or the Holders of not less than 25% in principal amount of the Outstanding Securities of that series fail to declare the principal amount (or, if the Securities of that series are Discount Securities, such portion of the
principal amount as may be specified in the terms of that series) of all the Securities of that series to be immediately due and payable, the holders of at least 25% in aggregate liquidation amount of the corresponding series of Preferred Securities
then outstanding shall have such right by a notice in writing to the Company and the Trustee; and upon any such declaration such principal amount (or specified portion thereof) of and the accrued interest (including any Additional Interest) on all
the Securities of such series shall become immediately due and payable. If an Event of Default specified in Section 5.1(4) or 5.1(5) with respect to Securities of any series at the time Outstanding occurs, the principal amount of all the Securities
of that series (or, if the Securities of that series are Discount Securities, such portion of the principal amount of such Securities as may be specified by the terms of that series) and the accrued interest (including any Additional Interest) on
such Securities shall automatically, and without any declaration or other action on the part of the Trustee or any Holder, become immediately due and payable. In case of any other Event of Default, there shall be no right to declare the principal
amount (or, if the Securities of that series are Discount Securities, such portion of the principal amount as may be specified in the terms of that series) of the Securities of that series to be due and payable immediately. Payment of principal and
interest (including any Additional Interest) on such Securities shall remain subordinated to the extent provided in Article XIII notwithstanding that such amount shall become immediately due and payable as herein provided. 
  

 4 

 ARTICLE III 
  
 MISCELLANEOUS 
  
 3.1. If any provision of this Supplemental Indenture limits, qualifies or conflicts with the duties imposed by any of Sections 310 to 317, inclusive, of
the Trust Indenture Act of 1939 through operation of Section 318(c) thereof, such imposed duties shall control. 
  
 3.2. The Article headings herein are for convenience only and shall not effect the construction hereof. 
  
 3.3. All covenants and agreements in this Supplemental Indenture by the
Company shall bind its successors and assigns, whether so expressed or not. 
  
 3.4. In case any provision of this Supplemental Indenture shall be invalid, illegal or unenforceable, the validity, legality and enforceability of the remaining provisions shall not in any way be affected or impaired
thereby. 
  
 3.5. Nothing in this Supplemental Indenture is
intended to or shall provide any rights to any parties other than those expressly contemplated by this Supplemental Indenture. 
  
 3.6. THIS SUPPLEMENTAL INDENTURE SHALL BE GOVERNED BY AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK. 
  
 3.7. The Trustee makes no representations as to the validity or sufficiency
of this Supplemental Indenture. The recitals and statements herein are deemed to be those of the Company and not of the Trustee. 
  

 5 

 * * * * 
  
 This instrument may be executed in any number of counterparts, each of which so executed shall be deemed to be an original, but all of which counterparts
shall together constitute but one and the same instrument. 
  
 IN
WITNESS WHEREOF, the parties hereto have caused this Supplemental Indenture to be duly executed, all as of the day and year first above written. 
  

			
	JPMORGAN CHASE & CO.
		
	By	 	 /s/ Louis M. Morrell

	Name:	 	Louis M. Morrell
	Title:	 	Managing Director
	
	 THE BANK OF NEW YORK
 as
Trustee

		
	By	 	 /s/ Kisha A. Holder

	Name:	 	Kisha A. Holder
	Title:	 	Asst. Vice President

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