UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`BIOEQ IP AG
`
`Petitioner
`
`v.
`
`GENENTECH, INC.
`
`Patent Owner
`
`_____________________
`
`Case No. IPR2016-01608
`
`U.S. Patent No. 6,716,602
`_____________________
`
`PETITIONER'S REPLY TO PATENT OWNER'S PRELIMINARY
`RESPONSE
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`BIOEQ IP AG
`
`Petitioner
`
`v.
`
`GENENTECH, INC.
`
`Patent Owner
`
`_____________________
`
`Case No. IPR2016-01608
`
`U.S. Patent No. 6,716,602
`_____________________
`
`PETITIONER'S REPLY TO PATENT OWNER'S PRELIMINARY
`RESPONSE
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`Petitioner’s Reply to Patent Owner’s
` Preliminary Response IPR2016-01608
`Petitioner submits this Reply to address corrections to claims 14, 16, 21, 25,
`
`28, and 38 of the '602 patent (BEQ1001), newly introduced by Patent Owner's
`
`December 1, 2016 Request for Certificate of Correction Under 35 U.S.C. § 254
`
`(EX2009). Petitioner confirms that its Petition (Paper 3) challenges claims 14, 16,
`
`25, 28, and 38 as-issued, and this Reply, authorized by the Board, demonstrates
`
`how the claims as presented in EX2009 are unpatentable. Petitioner also seeks to
`
`add claim 21 to its original Ground 1—but for Patent Owner's dilatory efforts to
`
`file its Request, Petitioner would have challenged claim 21 in its Petition.
`
`I.
`
`Seeger anticipates claims 16, 25, and 28
`
`Seeger anticipates claims 16, 25, and 28—amended or not. Amended claims
`
`16 and 25 include the same step (b) and same terminal "wherein" clause recited in
`
`claim 1, modified to refer to "antibody, growth factor, or protease" (claim 16) or
`
`"mammalian polypeptide" (claim 25). (EX2009, 2, 3, 7; BEQ1001, 18:23-24.)
`
`Claim 28 would depend from claim 25, not 27. (EX2009, 3, 7; BEQ1001, 20:1-2.)
`
`As explained in the Petition and Declaration (BEQ1002), Seeger anticipates claims
`
`16, 25, and 28. (Paper 3, 28-41; BEQ1002, ¶¶68-74; 88-89; 98-99; 103-104.)
`
`Seeger discloses every element of claims 16, 25, and 28, arranged as claimed
`
`and in a manner enabling to a POSA. (Paper 3, 28-41; BEQ1002, ¶¶68-74; 88-89;
`
`98-99; 103-104.) The Petition and Declaration show that Seeger describes
`
`inducible expression of mammalian growth factor bFGF in recombinant host cells,
`
`1
`
`
`
`
`
`
`by first culturing the cells "under conditions of high metabolic and growth rate,"
`
`Petitioner’s Reply to Patent Owner’s
`Preliminary Response in IPR2016-01608
`
`and then "reducing the metabolic rate of the host cells at the time of induction" by
`
`reducing the amount of available glucose. (Paper 3, 29, 32-35; BEQ1010, 951:2:1,
`
`950:2, Figure 3; BEQ1002, ¶¶4, 29, 52-57, 68-69, 71-72, 76). Dr. Rosenberg's
`
`calculations show that reducing available glucose resulted in a reduction in the host
`
`cells' specific glucose uptake rate (GUR). (Paper 3, 34-35; EX1002, ¶56.) Indeed
`
`"a reduction in [] GUR represents a reduction in the metabolic rate." (Paper 3, 34-
`
`35; BEQ1002, ¶71.) Thus, the Petition shows that Seeger reduced metabolic rate of
`
`the cells at the time of induction.
`
`Genentech posits that Dr. Rosenberg's GUR calculation "does not reflect the
`
`true metabolic rate" of Seeger's cells because it "ignores the effects of the
`
`temperature increase on the metabolic rate." (Paper 9, 27-28). Genentech is wrong.
`
`As Dr. Rosenberg explains, "a metabolic rate of a bacterial cell is closely related to
`
`a rate with which the cell consumes and oxidizes [] glucose," e.g., GUR.
`
`(BEQ1002, ¶37; Paper 3, 8.) And, "a magnitude of change in GUR [] can serve as
`
`a proxy for the magnitude of change in a metabolic rate." (BEQ1002, ¶81; Paper 3,
`
`41.) Thus, GUR is a "read-out" of the cells' metabolic rate. It accounts for any
`
`external factors that influence the metabolic rate—amount of supplied glucose,
`
`oxygen, or temperature. Dr. Rosenberg calculated GUR throughout Seeger's fed-
`
`batch phases, i.e., before and after the temperature change that induced bFGF
`
`2
`
`
`
`
`
`
`expression, thus accounting for temperature. (Paper 3, 34-35; BEQ1002, ¶56.)
`
`Petitioner’s Reply to Patent Owner’s
`Preliminary Response in IPR2016-01608
`
`Indeed, “when the temperature was raised from 30° to 42°C [in Seeger’s method],
`
`there was a reduction in the actual growth rate.” (BEQ1020, 64.)
`
`Seeger also teaches the added "wherein" clause of claims 16 and 25. (Paper
`
`3, 36-37; BEQ1002, ¶¶43, 55, 57, 73.) This clause imparts no patentable weight—
`
`it is an intended outcome. (Paper 3, 20-21, 36.) Indeed, Genentech itself admits
`
`unequivocally that "a reduction in metabolic rate at the time of induction will result
`
`in an increased yield of properly folded polypeptide." (Paper 9, 16, emphasis
`
`added.) But even if considered a limitation, Seeger teaches the "wherein" clause.
`
`Dr. Rosenberg explains that shifting the exponential glucose feeding rate at
`
`the time of induction resulted in an increased bFGF expression in a soluble
`
`fraction—from zero without the shift. (Paper 3, 37; BEQ1002, ¶¶43, 57, 73.) A
`
`POSA would have understood that the soluble fraction contained properly-folded
`
`bFGF. (Paper 3, 37; BEQ1002, ¶73.) And Genentech agrees: "a POSA would have
`
`understood that the soluble fraction of a cell lysate would contain properly folded
`
`polypeptide of interest." (Paper 9, 15, emphasis added.) Indeed, Seeger’s goal was
`
`to “optimize the production of soluble and thus biologically active bFGF.”
`
`(BEQ1020, 80.) Claims 16 and 25 do not require a percentage of properly-folded
`
`polypeptide—any increase in properly folded polypeptide is within the scope of
`
`claims 16 and 25.
`
`3
`
`
`
`
`
`
`II.
`
`Petitioner’s Reply to Patent Owner’s
`Preliminary Response in IPR2016-01608
`
`Seeger renders obvious claims 14 and 38
`
`The proposed corrections to claims 14 and 38 leave intact the phrase "the
`
`polypeptide is selected from the group consisting of an Fab'2 antibody and an Fab
`
`antibody." (EX2009, 7; BEQ1001, 18:52-54, 20:27-29; BEQ1002, ¶¶18:52-54,
`
`20:27-29.) The Petition and Dr. Rosenberg's Declaration confirm that a POSA
`
`reading Seeger and Cabilly, would have had a reason to produce Fab antibody
`
`fragments as recited in claims 14 and 38, with a reasonable expectation of success.
`
`(Paper 3, 53-57; BEQ1002, ¶¶144-163.) Genentech does not dispute these
`
`teachings, and instead argues that Seeger teaches away. (Paper 9, 37.) But it does
`
`not. Teaching away is measured in the art as a whole. Medichem, S.A. v. Rolabo,
`
`S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2016). And Seeger clearly describes
`
`decreasing the exponential feeding rate—and thus the metabolic rate—at the time
`
`of induction to produce soluble, properly-folded bFGF protein.
`
`III. Seeger anticipates claim 21
`Amended claim 21 would depend from claim 20 instead of claim 19.
`
`(EX2009, 3, 4, 7; BEQ1001, 19:11-12.) The Petition did not challenge claim 19
`
`but did challenge claim 20. (Paper 3, 40.) Because Patent Owner now seeks to
`
`amend claim 21, Petitioner requests that the Board also institute IPR of claim 21.
`
`Claim 21 states that "the carbon/energy source is glucose." (EX2009, 3, 4;
`
`BEQ1001, 19:11-12.) Seeger teaches a glucose carbon/energy source, anticipating
`
`4
`
`
`
`
`
`
`claim 21. (Paper 3, 28; BEQ1002, ¶¶77-78, 103-104.) And Petitioner challenged
`
`Petitioner’s Reply to Patent Owner’s
`Preliminary Response in IPR2016-01608
`
`the same limitation in claims 4 and 28 (Paper 3, 40-41; BEQ1002, ¶¶77-78):
`
`
`Challenged
`dependent claim
`
`Depends from
`
`Depends from
`
`
`4
`
`3
`
`1
`
`
`21
`
`
`28
`
`20
`
`27
`
`16
`
`25
`
`Seeger (BEQ1010) describes each element:
`
`949:1:1, 950:2, Figure 3 legend, 952:1, Table 2
`
`951:2:1-2, 950:2, Figure 3 legend
`
`947, Abstract, 948:1:3, 948, Table 1, 948:2:1-3,
`950:2, 951:2:1-2, 952:1:1-952:2:2, 953:1:2
`
`The Board has discretion to find claim 21 unpatentable in view of the prior
`
`art and information provided in the Petition.[1] Cuozzo Speed Techs, LLC v. Lee,
`
`136 S. Ct. 2131, 2140 (2016). Any prejudice to Patent Owner by such a finding is
`
`minimal because the Petition provided notice that a glucose carbon source is in the
`
`art. The same cannot be said for Petitioner. Had Patent Owner corrected claim 21
`
`in the more than 12 years since issuance, the Petition would have included the
`
`claim. It is manifestly unjust to reward Patent Owner’s delay by not adding claim
`
`21 here.
`
`
`
`Respectfully submitted,
`STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
`
`Date: December 9, 2016
`1100 New York Avenue, N.W.
`Washington, DC 20005-3934
`(202) 371-2600
`
`[1] The excess claim fee ($600) for claim 21 is paid with this filing.
`
`l
`Deborah A. Sterling
`Registration No. 62,732
`Lead Attorney for Petitioner
`
`5
`
`
`
`
`
`
`Petitioner’s Reply to Patent Owner’s
` Preliminary Response IPR2016-01608
`CERTIFICATION OF SERVICE (37 C.F.R. §§ 42.6(e), 42.105(a))
`
`The undersigned hereby certifies that the above-captioned "Petitioner’s
`
`Reply to Patent Owner’s Preliminary Response" was served in its entirety on
`
`December 9, 2016, upon the following counsel of record via electronic mail:
`
`jengordon@paulweiss.com
`sbalcof@paulweiss.com
`
`PAUL, WEISS, RIFKIND,
`WHARTON &
`GARRISON LLP
`1285 Avenue of the Americas
`New York, NY 10019
`
`
`
`
`Respectfully submitted,
`STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
`
`l
`Deborah A. Sterling
`Registration No. 62,732
`Lead Attorney for Petitioner
`
`dball@paulweiss.com
`
`
`
`PAUL, WEISS, RIFKIND,
`WHARTON &
`GARRISON LLP
`2001 K Street, NW
`Washington, DC 20006-1047
`
`
`
`
`
`
`Date: December 9, 2016
`1100 New York Avenue, N.W.
`Washington, DC 20005-3934
`(202) 371-2600
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
