Document:

Exhibit 10.19

 

EIGHTH AMENDMENT TO AGREEMENT

 

This is the eighth amendment to the Research Collaboration and License
Agreement between MERCK & CO. INC., a corporation organized and
existing under the laws of New Jersey (“MERCK”) and ARRIS PHARMACEUTICAL CORPORATION,
a corporation organized and existing under the laws of Delaware, now known as
Axys Pharmaceuticals, Inc, (“Axys”) made as of November 6, 1996 (the “Agreement”).
The purpose of this eighth amendment is to extend the Research Program Term
through February 5, 2003,

 

1.                                       In accordance
with the provisions of Section 2.8 and Section 5.2 (d) of the
Agreement and subject to MERCK’s right to terminate the Research Program and
the Agreement in accordance with Section 8.2, the parties agree that the
Research Program Term is extended through February 5, 2003, and the
parties agree that [***] FTE’s will be required during the period [***],
payable pro-rata at an annual rate of [***] per FTE.

 

2.                                       Attachment 2.1
setting forth the Research Program is hereby amended to include the revised
Work Plan set forth in the attachment to this Eighth Amendment. The parties
agree that the [***] FTE’s provided for in this Amendment will be required to
complete the Work Plan by February 2, 2003.

 

3.                                       Capitalized
terms used and not otherwise defined herein shall have the respective meanings
set forth in the Agreement. The Agreement, together with the first amendment
dated February 9, 1998, the second amendment dated November 5, 1998,
the third amendment dated November 18, 1999, the fourth amendment dated March 3,
2000, the fifth amendment dated November 10, 2000, the sixth amendment
dated January 5, 2001, the seventh amendment dated November 3, 2001
and this eighth amendment contain the entire understanding of the parties with
respect to their subject matter. All express or implied agreements and
understandings, either oral or written, heretofore made are expressly merged in
and made a part of the Agreement as amended by the first, second, third,
fourth, fifth, sixth, seventh and eighth amendments. All other terms and
conditions of the Agreement, as amended, continue in full force and effect. The
Agreement and its amendments may be amended, or any term thereof modified, only
by a written instrument duly executed by both parties hereto.

 

IN WITNESS WHEREOF, the parties have entered into this Amendment as of
the date of the last party to sign below.

 

	
  MERCK & CO., INC,

  	
   

  	
  AXYS PHARMACEUTICALS, INC.

  
	
   

  	
   

  	
   

  
	
  BY:

  	
  /s/ Kathleen Metters

  	
   

  	
  BY:

  	
  [illegible signature]

  
	
  TITLE:

  	
  Vice President

  	
   

  	
  TITLE:

  	
  General Manager

  
	
  DATE:

  	
  Nov. 8, 2002

  	
   

  	
  DATE:

  	
  11/20/02

  

 

[***] indicates material that has been omitted pursuant to a request
for confidential treatment. The omitted material has been filed separately with
the Securities and Exchange Commission.

 

 

ATTACHMENT
2.1

 

RESEARCH
PROGRAM

 

Axys and Merck shall use commercially
reasonable efforts to complete the work outlined below by February 5, 2003,
which work was initiated during [***].

 

	
  1.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
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  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
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  5.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  6.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  7.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  8.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  a.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  b.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  c.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  d.

  	
   

  	
  [***]

  

 

[***] indicates material that has been omitted pursuant to a request
for confidential treatment. The omitted material has been filed separately with
the Securities and Exchange Commission.

 

 

Attachment 2.1

Research Program

 

APPENDIX A

 

[***]

 

[***] indicates material that has been omitted pursuant to a request
for confidential treatment. The omitted material has been filed separately with
the Securities and Exchange Commission.

 

2

 

Attachment 2.1

Research Program

 

APPENDIX B

 

[***]

 

[***] indicates material that has been omitted pursuant to a request
for confidential treatment. The omitted material has been filed separately with
the Securities and Exchange Commission.

 

3

 

Attachment 2.1

Research Program

 

APPENDIX C

 

[***]

 

[***] indicates material that has been omitted pursuant to a request
for confidential treatment. The omitted material has been filed separately with
the Securities and Exchange Commission.

 

4

 

Attachment 2.1

Research Program

 

APPENDIX D

 

[***]

 

[***] indicates material that has been omitted pursuant to a request
for confidential treatment. The omitted material has been filed separately with
the Securities and Exchange Commission.

 

5Exhibit 10.21

 

AMENDMENT NO. 1

 

to

 

ASSIGNMENT AGREEMENT

 

This AMENDMENT TO ASSIGNMENT AGREEMENT (“Amendment”),
effective as of May 12, 2008 (the “Amendment Date”),
is made and entered into by and between PHARMACYCLICS, INC.,
a Delaware corporation having a place of business at 995 East Arques Avenue,
Sunnyvale, California 94085, (“Pharmacyclics”)
and APPLERA CORPORATION, a Delaware
corporation, through its CELERA GROUP
having a place of business at 45 West Gude Drive, Rockville, Maryland 20850 (“Celera”).  Pharmacyclics and Celera may each be referred
to herein individually as a “Party” or,
collectively, as “Parties.”

 

WHEREAS, Pharmacyclics and Celera are parties to the
Assignment Agreement, effective as of April 7, 2006, whereby Celera
assigned to Pharmacyclics certain proprietary technology and know-how related
to the Celera Programs, including but not limited to the HDAC Program (the “Assignment Agreement”);

 

WHEREAS, Pharmacyclics desires that certain payment terms
of the Assignment Agreement relating to [***] be amended; and

 

WHEREAS, Celera desires that such payment terms should be
amended, subject to the terms and conditions set forth below.

 

NOW, THEREFORE, in consideration of the mutual covenants
and obligations set forth herein, and for other good and valuable
consideration, the receipt and sufficiency of which is hereby acknowledged,
Pharmacyclics and Celera hereby agree as follows:

 

1.                                      In
General.

 

All terms defined in the
Assignment Agreement shall have a meaning in this Amendment as in the Assignment
Agreement, unless otherwise expressly defined in this Amendment.

 

2.                                      Amendment
of the Assignment Agreement.

 

2.1          Amendment of Section 6.3.  Section 6.3 of the Assignment Agreement
is hereby amended to read in its entirety as follows;

 

6.3          Product
Milestones

 

(a)                                  Pharmacyclics will pay to Celera payments
as set forth in this Section 6.3 within thirty (30) days after (i) under
Section 6.3(b) and 6.3(c), Pharmacyclics’ receipt of upfront and
milestone payments from one or more Third Parties upon the grant by
Pharmacyclics of a sublicense to such Third Party under the Celera Technology
and the Celera Patents to make, use, offer to sell, sell and import any
Assigned Product which is an [***], and (ii) under Section 6.3(d),
the first achievement of the 

 

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

 

                                                corresponding milestone for an Assigned
Product which is an [***] or which is a [***]. 
Such payments shall be made in Dollars by wire transfer of immediately
available funds into an account designated by Celera.  No achievement milestone payment will be
payable more than once, no matter how many times such milestone is achieved by
a single Assigned Product or by multiple Assigned Products in each of the [***]
category or the [***] category.  Such
payments will be nonrefundable and non-creditable against Royalties payable
pursuant to Sections 6.4, and any other fees, milestone payments or other
payments due Celera under this Agreement.

 

(b)                                  Subject to the terms and conditions of this Agreement,
in the event that Pharmacyclics, within two years of the Amendment Date, grants
a sublicense to one or more Third Parties under the Celera Technology and the
Celera Patents to make, use, offer to sell, sell and import any Assigned
Product which is an [***], Pharmacyclics will pay to Celera [***] from such
Third Parties.  For purposes of this Section 6.3(b) and
Section 6.3(c), the term “[***]” does not include [***].

 

(c)                                  Subject to the terms and conditions of
this Agreement, in the event that Pharmacyclics, at any time subsequent to two
years after the Amendment Date, grants a sublicense to one or more Third
Parties under the Celera Technology and the Celera Patents to make, use, offer
to sell, sell and import any Assigned Product which is an [***], Pharmacyclics
will pay to Celera the greater of (i) [***]% of [***] from such Third
Parties, [***] or (ii) [***]% of [***] received from such Third Party. The
foregoing amounts will be determined as and when Pharmacyclics receives such
amounts and will take into account all payments received by Pharmacyclics as
described in this Section 6.3(c). For purposes of this Section 6.3(c),
the term “[***]” means [***].

 

                                                For example: if Pharmacyclics has paid
Celera [***] due to Celera from an initial Third Party sublicense agreement
through 6.3(c)(i), but then enters into a second Third Party sublicense
agreement where Pharmacyclics receives from such Third Party [***],
Pharmacyclics would [***].

 

(d)                                  Subject to the terms and conditions of
this Agreement, Pharmacyclics will pay Celera milestone payments in accordance
with the following table:

 

	
  Milestone Event

  	
   

  	
  Milestone Payment Amount (Dollars)

  	
   

  
	
   

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  1.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  2.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  3.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  4.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  5.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  6.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
  7.  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  	
  $

  	
  [***]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total

  	
   

  	
  $

  	
  72
  million

  	
   

  	
  $

  	
  32
  million

  	
   

  

 

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

2

 

2.2          Amendment of Section 6.4.  Section 6.4 of the Assignment Agreement
is hereby amended to read in its entirety as follows;

 

6.4          Royalties

 

(a)                                  Subject to the terms and conditions of this Agreement,
Pharmacyclics will pay Celera a tiered Royalty in accordance with the following
table on worldwide Net Sales:

 

	
  Total Net Sales of an Assigned 

  Product in a Calendar Year

  	
   

  	
  Percent of Net Sales

  	
   

  
	
   

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***] to $[***]

  	
   

  	
  [***]

  	
  %

  	
  [***]

  	
  %

  	
  [***]

  	
  %

  
	
  $[***] to $[***]

  	
   

  	
  [***]

  	
  %

  	
  [***]

  	
  %

  	
  [***]

  	
  %

  
	
  Above $[***]

  	
   

  	
  [***]

  	
  %

  	
  [***]

  	
  %

  	
  [***]

  	
  %

  

 

(b)                                  Notwithstanding Section 6.4(a) as
applied to [***], subject to the terms and conditions of this Agreement, in the
event that Pharmacyclics, grants a sublicense to one or more Third Parties
under the Celera Technology and the Celera Patents to make, use, offer to sell,
sell and import any Assigned Product which is an [***], Pharmacyclics will pay
to Celera a Royalty with respect to sales of such sublicensed [***] equal to
the greater of (i) [***] percent ([***]%) of any royalties on sales of
such sublicensed [***] received by Pharmacyclics from such Third Parties or (ii) [***]%
of worldwide Net Sales of such sublicensed [***] sold by such Third Parties. In
each case (i) and (ii) above, no payments will be due or payable by 

 

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

3

 

                                                Pharmacyclics to Celera under Section 6.4(a) with
respect to sales of such sublicensed [***] by such Third Parties.  For purposes of clarification, Pharmacyclics
will pay to Celera the Royalties set forth in Section 6.4(a) on Net
Sales of such [***] sold by or through Pharmacyclics, other than through the
above-described sublicenses.

 

(c)                                  Pharmacyclics may deduct from Royalties
payable to Celera pursuant to Sections 6.4(a) and/or 6.4(b), as
applicable, up to [***] percent ([***]%) of any amounts paid to Third Parties
to obtain licenses or other rights under any Patents to the extent that,
without such licenses or rights, Pharmacyclics cannot otherwise make, use,
sell, offer for sale, or import the applicable Assigned Product without
infringing a claim of such Patent; provided that, after such deduction, the
amount paid to Celera is not less than [***] percent ([***]%) of the amount
that would otherwise have been paid to Celera pursuant to Sections 6.4(a) or
6.4(b), as applicable.  As a condition to
benefiting from this Section 6.4(c), Pharmacyclics must deliver to Celera
a true copy of each agreement with a Third Party that Pharmacyclics contends is
subject to this Section 6.4(c). 
Each such agreement shall be treated by Celera as Pharmacyclics’
Confidential Information.

 

3.                                      Reference
to and Effect on the Assignment Agreement.

 

3.1          Pursuant to Section 13.1 of the
Assignment Agreement, this Amendment shall be effective upon the Amendment
Date, whereupon the Assignment Agreement shall be, and hereby is, amended as
set forth herein.

 

3.2          On and after the Amendment Date, each
reference in the Assignment Agreement to “this Agreement,” “hereunder,” “hereof,”
“herein” or words of like import shall mean and be a reference to the
Assignment Agreement as amended hereby. 
No reference to this Amendment need be made in any instrument or
document at any time referring to the Assignment Agreement, a reference to the
Assignment Agreement in any of such to be deemed to be a reference to the
Assignment Agreement as amended hereby.

 

3.3          All provisions of the Assignment
Agreement not expressly modified by this Amendment shall remain in full force
and effect.

 

4.                                      Counterparts.

 

This Amendment may be
executed in one or more counterparts, each of which shall be deemed to be an
original, but all of which together shall constitute a single instrument.

 

Signature Page Follows

 

 

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

4

 

IN WITNESS THEREOF, the Parties have caused
this Amendment to be duly executed by their respective duly authorized officers
as of the Amendment Date.

 

	
  PHARMACYCLICS,
  INC.

  (“Pharmacyclics”)

  	
   

  	
  APPLERA
  CORPORATION through its 

  CELERA GROUP

  (“Celera”)

  

 

	
  By:

  	
   /s/ Richard A. Miller

  	
   

  	
  By:

  	
   /s/ Victor K. Lee

  

 

	
  Print Name:    Richard A. Miller

  	
   

  	
  Print Name:    Victor K. Lee, Ph.D.

  

 

	
  Title:    Pres + CEO

  	
   

  	
  Title:    Assistant Secretary

  

 

 

 

 

Signature Page to Amendment No. 1 to Assignment Agreement

 

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

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