Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 1 of 13 PageID #:
`34525
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`GENENTECH, INC. and CITY OF
`HOPE,
`
`C.A.No. 17-1407-CFC-SRF
`(CONSOLIDATED)
`
`v.
`AMGEN INC.,
`
`Plaintiffs,
`
`Defendant.
`
`GENENTECH, INC.,
`
`v.
`AMGEN INC.,
`
`Plaintiff,
`
`Defendant.
`
`C.A. No. 18-924-CFC-SRF
`REDACTED
`PUBLIC VERSION
`
`AMGEN INC.’S LETTER RESPONSE REGARDING COURT’S
`CONSTRUCTION OF “FOLLOWING FERMENTATION”
`C.A. No. 17-1407-CFC-SRF:
`C.A. No. 18-924-CFC-SRF:
`
`YOUNG, CONAWAY, STARGATT
`& TAYLOR LLP
`Melanie K. Sharp (No. 2501)
`James L. Higgins (No. 5021)
`Rodney Square
`1000 North King Street
`Wilmington, DE 19801
`P (302) 571-6600
`msharp@ycst.com
`jhiggins@ycst.com
`
`Attorneys for Defendant Amgen Inc.
`
`Dated: February 26, 2020
`
`SMITH, KATZENSTEIN &
`JENKINS, LLP
`Neal C.Belgam (No. 2721)
`Eve H. Ormerod (No. 5369)
`Jennifer M. Rutter (No. 6200)
`1000 West Street, Suite 1501
`Wilmington, DE 19801
`P(302)652-8400
`nbelgam@skjlaw.com
`eormerod@skjlaw.com
`jrutter@skjlaw.com
`
`Attorneys for Defendant Amgen Inc.
`
`26086383.1
`
`
`34525
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`GENENTECH, INC. and CITY OF
`HOPE,
`
`C.A.No. 17-1407-CFC-SRF
`(CONSOLIDATED)
`
`v.
`AMGEN INC.,
`
`Plaintiffs,
`
`Defendant.
`
`GENENTECH, INC.,
`
`v.
`AMGEN INC.,
`
`Plaintiff,
`
`Defendant.
`
`C.A. No. 18-924-CFC-SRF
`REDACTED
`PUBLIC VERSION
`
`AMGEN INC.’S LETTER RESPONSE REGARDING COURT’S
`CONSTRUCTION OF “FOLLOWING FERMENTATION”
`C.A. No. 17-1407-CFC-SRF:
`C.A. No. 18-924-CFC-SRF:
`
`YOUNG, CONAWAY, STARGATT
`& TAYLOR LLP
`Melanie K. Sharp (No. 2501)
`James L. Higgins (No. 5021)
`Rodney Square
`1000 North King Street
`Wilmington, DE 19801
`P (302) 571-6600
`msharp@ycst.com
`jhiggins@ycst.com
`
`Attorneys for Defendant Amgen Inc.
`
`Dated: February 26, 2020
`
`SMITH, KATZENSTEIN &
`JENKINS, LLP
`Neal C.Belgam (No. 2721)
`Eve H. Ormerod (No. 5369)
`Jennifer M. Rutter (No. 6200)
`1000 West Street, Suite 1501
`Wilmington, DE 19801
`P(302)652-8400
`nbelgam@skjlaw.com
`eormerod@skjlaw.com
`jrutter@skjlaw.com
`
`Attorneys for Defendant Amgen Inc.
`
`26086383.1
`
`
`
`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 2 of 13 PageID #:
`34526
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`Dear Judge Connolly:
`
`In its February 18, 2020 Oral Order, the Court informed the parties that it is
`
`inclined to construe “following fermentation” to mean “after harvesting has
`
`begun.” Adhering to the Court’s admonition in inviting a response, Amgen
`
`responds as follows.
`
`The Court’s construction of “following fermentation” reflects the
`
`specification’s description of the purported invention as preventing disulfide bond
`
`reduction at a particular point in the manufacturing process after harvesting has
`
`begun—not during processes occurring in the production vessels: “In particular,
`
`the invention concerns the prevention of disulfide bond reduction during
`
`harvesting of disulfide-containing polypeptides, including antibodies, from
`
`recombinant host cell cultures.” (’869 Patent at 1:19-22, D.I. 516, C.A. 17-1407, at
`
`Appx42; D.I. 376, C.A. 18-924, at Appx42.) “In particular, the invention concerns
`
`methods for preventing the reduction of disulfide bonds of recombinant proteins
`
`during processing following fermentation.” (Id. at 20:9-11.)
`
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 3 of 13 PageID #:
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`Figure 23 of the ’869 Patent (copied below) depicts the distinction between
`
`fermentation and harvest, indicating that harvest comes after the culture fluid has
`
`left the production vessels. {Id. at Fig. 23 (highlight added).)
`
`Typical Batch or Fed-Batch Culture Process
`
`Seed Tram
`Multiple Passages in
`Selective Medium
`
`Inoculum Train
`Multiple Passages in
`Non*Selective Medium
`
`Production
`Non-Selective
`Production Medium
`
`Temperature
`Seeding density
`Culture duration
`
`d02, pH, Temperature
`Seeding density
`Culture duration
`
`dC>2, pH. Temperature
`Parameter shifts & timing
`Osmolality
`Batch feed addition
`Seedira density
`Culture duration
`
`FIG. 23
`
`The patent also provides examples of addressing disulfide bond reduction
`
`following completion of the cell culture process by treating the fluid during and/or
`
`after the harvest process: “Disulfide bond reduction can be inhibited (i.e., partially
`
`or fully blocked) by using one or more Trx inhibitors and/or applying non-directed
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`approaches [e.g., air sparging] following completion of the cell culture process,
`
`preferably to CCF prior to harvest [i.e., pre-harvest culture fluid] or in the HCCF
`
`immediately after harvest [i.e., harvested culture fluid].” {Id. at 23:54-58.)
`
`Amgen does not sparge culture fluid that has left the bioreactor. Thus, under
`
`the construction of “following fermentation” as “after harvesting has begun,”
`
`Genentech will have no objective basis to continue its infringement allegations in
`
`
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 4 of 13 PageID #:
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`the above-captioned cases. Genentech, however, refuses to yield.
`
`On the heels of the Court’s proposed construction, Amgen initiated a meet
`
`and confer to confirm that the construction, once made final, would finally compel
`
`Genentech’s withdrawal of its ’869 Patent infringement claims. But Genentech
`
`indicated that such a construction would merely ignite further dispute over the
`
`meaning of “harvesting.” Genentech further indicated—contrary to basic canons of
`
`claim construction—that it will at that time seek to define “harvesting” in light of
`
`| not by the understanding of the ordinary artisan at the time of the
`
`purported invention and in light of the ’869 Patent specification.1
`
`Genentech’s effective promise to foment continuing dispute in the hope of
`
`pouring a self-serving, after-the-fact meaning into “harvesting” regrettably requires
`
`resolution at the claim construction stage. 02 Micro Int’l Ltd. v. Beyond
`
`Innovation Tech. Co., Ltd., 521 F.3d 1351, 1362-63 (Fed. Cir. 2008).
`
`The solution, however, is straightforward. Amgen requests that the Court
`
`simply make explicit what is already implicit in its construction, i.e., that
`
`“harvesting” is “separating of cells or cellular debris from culture fluid using
`
`1 “[A] court may not use the accused product or process as a form of extrinsic
`evidence to supply limitations for patent claim language.” Wilson Sporting Goods
`Co. v. Hillerich & Bradsby Co., 442 F.3d 1322, 1331 (Fed. Cir. 2006).
`
`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 5 of 13 PageID #:
`34529
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`centrifugation or filtration.” This flows not only from the instrinsic evidence, but
`
`from Genentech’s own admissions.
`
`The patent explains that “[fallowing fermentation proteins are purified.”
`
`(’869 Patent at 26:41.) The “[procedures for purification of proteins” include
`
`“centrifugation” or “filtration.” {Id. at 26:41, 26:52-53.)
`
`The patent further explains in its background section that, “[tjypically,
`
`harvesting includes centrifugation and filtration to produce a Harvested Cell
`
`Culture Fluid (HCCF).” (’869 Patent at 2:3-4.) The patent reiterates in its
`
`“Compositions and Methods of the Invention” section that the “harvested cell
`
`culture fluid (HCCF) ... is obtained after harvesting by centrifugation, filtration, or
`
`similar separation methods.” {Id. at 22:3-5.)
`
`In the context of the claim language, “pre-harvest ... culture fluid” refers to
`
`the fluid that is sparged, not the timing of sparging. To fall within the claimed
`
`method under the Court’s proposed construction of “following fermentation,” the
`
`“pre-harvest ... culture fluid” must be sparged after harvesting has begun, i.e., in
`
`the centrifuge or filtration system where separation of the cells or cellular debris
`
`from the fluid begins.
`
`In written testimony, oral testimony, briefing, and counsel’s argument to the
`
`Court, Genentech has itself confirmed that “harvesting” is the separation of cells
`
`and cellular debris from culture fluid through centrifugation or filtration.
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`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 6 of 13 PageID #:
`34530
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`Genentech’s expert, Dr. Hauser, acknowledged in his claim construction
`
`declaration that “[t]he purpose of this [harvesting] process is to remove the cells
`
`from the culture fluid to produce a ‘clarified’ solution.” (D.I. 326, Declaration of
`
`Hansjorg Hauser, at^j 43, J.A. 806; D.I. 104, C.A. 18-924 (same)).
`
`During the October 16, 2019 hearing, Genentech and Dr. Hauser
`
`distinguished fermentation from harvesting by referencing a representative
`
`schematic from the Birch reference (copied below) showing a series of production
`
`bioreactors (also called “fermenters”) followed by a distinct harvesting sequence
`
`involving separation though centrifugation and/or filtration steps. (D.I. 516, C.A.
`
`17-1407, at Appx213; D.I. 376, C.A. 18-924, at Appx213.)
`
`Train A
`
`Train B
`
`Train C
`
`" 0
`
`______
`
`Tt IT IT TT
`
`k /T
`
`Centrifuge
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`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 7 of 13 PageID #:
`34531
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`Before the Court, Dr. Hauser clearly delineated fermentation from
`
`harvesting:
`
`Q. And what goes on in the fermenter [/.e., royal blue-colored
`vessels in the top line of figure]?
`DR. HAUSER. Fermenter activity is mainly cell growth, end of
`production.
`Q. And what happens in the next line of the figure in Birch?
`DR. HAUSER: The next line concerns the harvesting, and this
`is a removal of cells from the cell culture fluid.
`(10/16/2019 Tr. at 54:15-21.)
`
`Tellingly, under the Court’s later examination, Dr. Hauser further confirmed
`
`that harvesting consists of centrifugation and filtration and does not occur until the
`
`culture fluid has left the bioreactor:
`
`THE COURT: All right. Where does harvesting occur in this
`slide?
`DR. HAUSER: Harvesting is the whole process that is given on
`the second line. The wheel process — you see here two different
`things. On the right you see the centrifuge.
`THE COURT: Yes.
`DR. HAUSER: That's one way to harvest. Very often there are
`also filters that are the two yellow things that are also used in
`order to clarify cell culture fluid. So altogether, this is called
`harvesting.
`{Id. at 111:14-19.)
`
`At the October 16, 2019 hearing, Genentech’s counsel similarly admitted
`
`that “harvest ... is the separating of the liquid from the cells. ...” (10/16/2019 Tr.
`
`at 191:2-3.) And in post-hearing briefing, Genentech again confirmed that
`
`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 8 of 13 PageID #:
`34532
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`“‘[hjarvesf is the process of separating the culture fluid (which contains the
`
`antibody) from cells or cellular debris.” (D.I. 570, C.A. 17-1407, at 1; D.I. 449,
`
`C.A. 18-924, at 1.)
`
`Centrifuges and filtration systems, as depicted in the second line of the Birch
`
`figure, are the equipment that separate cells and cellular debris from culture fluid.
`
`That is why the experts, parties, and the patent itself point to centrifuges and
`
`filtration systems for “harvesting.”2
`
`Because of Genentech’s refusal to acknowledge the implications of the
`
`Court’s proposed construction, and in accordance with 02 Micro, Amgen
`
`respectfully requests that the Court clarify its construction of “following
`
`fermentation” to make the nature of “harvesting” explicit: “after separating of cells
`
`or cellular debris from culture fluid using centrifugation or filtration has begun.”
`
`2 While the patent also refers to unspecified “similar separation methods” for
`“harvesting,” (’869 Patent at 22:3-5), there is no reference anywhere in the patent
`to a bioreactor or fermenter being capable of separating cells or cellular debris
`from culture fluid similar to a centrifuge or filtration system. Accordingly, the
`“similar separation methods” cannot include fermentation in fermenters.
`
`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 9 of 13 PageID #:
`34533
`
`Dated: February 26, 2020
`
`YOUNG CONAWAY STARGATT &
`TAYLOR, LLP
`
`SMITH, KATZENSTEIN & JENKINS
`LLP
`
`/s/ James L. Higgins_________
`Melanie IC. Sharp (No. 2501)
`James L. Higgins (No. 5021)
`Steven W. Lee (No. 6676)
`Rodney Square
`1000 North King Street
`Wilmington, DE 19801
`(302) 571-6600
`msharp@ycst.com
`jhiggins@ycst.com
`slee@ycst.com
`
`Attorneys for Defendant Amgen Inc. in
`C.A. No. 17-1407-CFC
`
`/s/ Eve H. Ormerod__________
`Neal C. Belgam (No. 2721)
`Eve H. Ormerod (No. 5369)
`Jennifer M. Rutter (No. 6200)
`1000 West Street, Suite 1501
`Wilmington, DE 19801
`(302) 652-8400
`nbelgam@skjlaw.com
`eormerod@skj law.com
`j rutter@skj law. com
`
`Attorneys for Defendant Amgen Inc. in
`C.A. No. 18-924-CFC
`
`26086383.1
`
`-9-
`
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 10 of 13 PageID
`#: 34534
`
`WORD COUNT CERTIFICATION
`
`The undersigned counsel hereby certify that the LETTER RESPONSE
`
`REGARDING COURT’S CONSTRUCTION OF “FOLLOWING
`
`FERMENTATION” contains 1,253 words, which were counted by Eve H.
`
`Ormerod and James L. Higgins by using the word count feature in Microsoft
`
`Word, in 14-point Times New Roman font. The foregoing word count does not
`
`include the cover page or the counsel blocks.
`
`Dated: February 26, 2020
`
`/s/ Eve H. Ormerod
`Eve H. Ormerod
`
`/s/ James L. Higgins
`James L. Higgins
`
`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 11 of 13 PageID
`#: 34535
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`CERTIFICATE OF SERVICE
`
`I certify that on February 26, 2020, a copy of Amgen Inc.’s LETTER
`
`RESPONSE REGARDING COURT’S CONSTRUCTION OF “FOLLOWING
`
`FERMENTATION” was caused to be served by email on the following counsel:
`
`Michael P. Kelly
`Daniel M. Silver
`Alexandra M. Joyce
`MCCARTER & ENGLISH, LLP
`Renaissance Centre
`405 N. King Street, 8th Floor
`Wilmington, DE 19801
`mkelly@mccarter.com
`dsilver@mccarter.com
`ajoyce@mccarter.com
`
`[s/_ Eve H. Ormerod______
`Eve H. Ormerod (No. 5369)
`
`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 12 of 13 PageID
`#: 34536
`
`CERTIFICATE OF SERVICE
`
`1.
`
`I, James L. Higgins, Esquire, hereby certify that on February 26, 2020,1
`caused to be electronically filed a true and correct copy of Amgen Inc.’s Letter
`Response Regarding Court’s Construction of “Following Fermentation” with the
`Clerk of the Court using CM/ECF, which will send notification to the following
`counsel of record:
`Michael P. Kelly
`Daniel M. Silver
`McCarter & English, LLP
`Renaissance Centre
`405 N. King Street, 8th Floor
`Wilmington, DE 19801
`mkelly@mccarter.com
`dsilver@mccarter.com
`I further certify that on February 26, 2020,1 caused a copy of the foregoing
`document to be served on the above-listed counsel of record and on the following
`non-registered participants in the manner indicated:
`BY E-MAIL
`Paul B. Gaffney
`David I. Berl
`Thomas S. Fletcher
`Kyle E. Thomason
`Teagan J. Gregory
`C. Luke McCloud
`Kathryn S. Kayali
`Jonathan S. Sidhu
`D. Shayon Ghosh
`Jingyuan Luo
`Sumeet P. Dang
`William F. Hawkins
`Williams & Connolly LLP
`725 Twelfth St. NW
`Washington, DC 20005
`pgaffnev@wc.com
`
`Daralyn J. Durie
`Adam R. Brausa
`David F. McGowan
`Eneda Hoxha
`Eric C. Wiener
`Durie Tangri
`217 Leidesdorff Street
`San Francisco, CA 94111
`ddurie@durietangri.com
`abrausa@durietangri.com
`Ehoxha@durietangri.com
`ewiener@durietangri.com
`
`26086383.1
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`Case 1:18-cv-00924-CFC-SRF Document 525 Filed 03/03/20 Page 13 of 13 PageID
`#: 34537
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`dberl@wc.com
`tfletcher@wc.com;
`kthomason@wc.com
`tgregory@wc.com;
`hnccloud@wc.com
`kkayali@wc.com
`jsidhu@wc.com
`sghosh@wc.com
`jluo@wc.com
`sdang@wc.com
`
`Is/ James L. Higgins
`
`James L. Higgins (No. 5021)
`
`26086383.1
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`
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