`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`MILTENYI BIOMEDICINE GmbH and MILTENYI BIOTEC INC.
`Petitioner
`
`v.
`
`THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`Patent Owner
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IPR Trial No. IPR2022-00853
`U.S. Patent No. 9,464,140
`Issue Date: October 11, 2016
`
`Title: Compositions and Methods for Treatment of Cancer
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`PETITIONER’S REPLY TO PATENT OWNER’S PRELIMINARY
`RESPONSE
`
`
`
`
`
`
`
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`
`
`TABLE OF CONTENTS
`Porter is Prior Art .............................................................................................. 1
`I.
`II. Claim Construction ........................................................................................... 3
`A. Preamble of “Treating Cancer” ................................................................ 3
`B. “Anti-Tumor Effective Amount” ................................................................ 4
`III. The Board Should Not Deny Institution Under Section 325(d) ....................... 5
`
`
`
`
`
`i
`
`
`
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Biocon Pharma v. Novartis Pharms.,
`IPR2020-01263, Paper 12 (P.T.A.B. Feb. 16, 2021) ............................................ 5
`Eli Lilly v. Teva Pharms,
`8 F.4th 1331 (Fed. Cir. 2021) ............................................................................... 3
`Nelson Products v. Bal Seal Engineering,
`IPR2014-00573, Paper 9 (P.T.A.B. Sept. 29, 2014)............................................. 2
`Samsung Electronics Co. v. Evolved Wireless LLC,
`IPR2021-00943, Paper 9 (P.T.A.B. Dec. 1, 2021) ............................................... 5
`Sanofi-Aventis U.S. LLC v. Immunex Corp.,
`IPR2017-01879, Paper 19 (P.TA.B. Feb. 15, 2018) ............................................. 3
`Satco Products Inc. v. The Regents of the Univ. of California,
`IPR2021-00662, Paper 13 (P.T.A.B. Nov. 8, 2021) ............................................. 5
`Watson Labs., Inc. v. United Therapeutics Corp.,
`IPR2017-01621, Paper 10 (P.T.A.B. Jan. 11, 2018) ............................................ 2
`
`
`
`
`
`ii
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`As authorized by the Board, Petitioner submits this Reply to address three
`
`
`
`issues raised in Patent Owner’s (“PO”) Preliminary Response: (1) Porter as prior art;
`
`(2) claim construction; and (3) Section 325(d).
`
`I.
`
`Porter is Prior Art
`Porter discloses results for a clinical study that treated cancer patients with the
`
`prior art Campana CAR. Pet., 19-20; Junghans (Ex. 1002), ¶¶106-114. Other than
`
`attacking Porter’s status as prior art, PO has provided no argument against Ground 4.
`
`POPR, 41-42. Because there is sufficient evidence that the relevant Porter
`
`disclosures are “by another,” Ground 4 should be instituted.
`
`Non-inventor Dr. Adam Bagg is an author of Porter. Ex. 1012, 725. Relying
`
`upon a declaration from Dr. Bagg, PO argues that Dr. Bagg did not contribute to any
`
`disclosure in Porter that is relevant to obviousness. POPR, 42. Dr. Bagg, who is
`
`employed by PO, states in his declaration that “all of the portions of Porter cited by
`
`the Petitioners reflect the work of my co-authors and not me.” Ex. 2044, ¶7. PO’s
`
`argument and Dr. Bagg’s declaration are inconsistent with Porter itself, which states
`
`that Dr. Bagg determined the anti-tumor effect reported in the paper.
`
`In its Protocol section, Porter describes Dr. Bagg as evaluating effectiveness
`
`by performing “MRD assessments” after CAR T-cell therapy. Ex. 1013, 36. MRD
`
`(or minimal residual disease) assessments refer to the measurement of residual tumor
`
`cells remaining in the body after treatment, which is relevant to anti-tumor
`
`
`
`1
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`
`effectiveness. Porter states: “Subjects will undergo … MRD assessments by
`
`Dr. Bagg” on “[d]ay 28” following CAR T-cell therapy. Id., 37. Dr. Bagg’s
`
`declaration also acknowledges that he “determined the laboratory result indicating
`
`remission ….” Ex. 2044, ¶8. Petitioner cited the antitumor effect disclosed in Porter
`
`as supporting obviousness. Pet., 65-66.
`
`At the very least, Dr. Bagg’s declaration raises factual questions about
`
`whether a portion of Porter, e.g., determination of antitumor effect, was “by
`
`another.” The Board has consistently instituted proceedings when patent owners
`
`submit testimony attempting to disqualify prior art in preliminary responses.
`
`In Nelson, the Board “decline[d] to disqualify” prior art when presented with
`
`a declaration from a prior-art author, Mr. Poon, to argue that relied-upon portions of
`
`the reference were not “by another.” Nelson Products v. Bal Seal Engineering,
`
`IPR2014-00573, Paper 9 at 9-12 (P.T.A.B. Sept. 29, 2014). The Board instituted,
`
`holding that “[o]n this record, we have no reason to doubt Mr. Poon’s credibility,
`
`however, we hesitate to rely solely on Mr. Poon’s testimony at this stage of the
`
`proceeding where it would result in a final, non-appealable denial of institution on a
`
`ground of unpatentability.” Id., 11. The Board has come to similar conclusions in
`
`other decisions. See, e.g., Watson Labs., Inc. v. United Therapeutics Corp.,
`
`IPR2017-01621, Paper 10, 11-14 (P.T.A.B. Jan. 11, 2018) (finding that “for the
`
`purposes of institution … Petitioner has provided a sufficient basis on which to
`
`
`
`2
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`
`conclude that [the journal article] was the work of another” despite the patent
`
`owner’s pre-institution declarations); Sanofi-Aventis U.S. LLC v. Immunex Corp.,
`
`IPR2017-01879, Paper 19, 14 (P.TA.B. Feb. 15, 2018) (accord).
`
`II. Claim Construction
`A.
`Preamble of “Treating Cancer”
`PO relies on Eli Lilly v. Teva Pharms, 8 F.4th 1331 (Fed. Cir. 2021), to argue
`
`that “treating cancer” in the preamble is limiting. POPR, 17-19. But the preambles
`
`in Eli Lilly were limiting because they “provide the only metric by which one
`
`practicing the claim could determine whether the amount administered is an
`
`‘effective amount,’” a term in the claim body. Id. at 1342. Unlike Eli Lilly, the claim
`
`body here already has a term, “anti-tumor effective amount,” that is well-defined by
`
`the specification and provides sufficient guidance for determining effectiveness. See
`
`Pet., 13-15. Eli Lilly left undisturbed precedent that preamble language is not
`
`limiting unless it recites essential structure or steps, or is necessary to understand the
`
`remaining limitations. Pet., 11-13. “Treating cancer” serves none of these purposes.
`
`And even if “human patient” in the preamble provides an antecedent, that does not
`
`make “treating cancer” limiting. Id. 12-13.
`
`Moreover, the POPR contains no evidence to rebut Petitioner’s point that,
`
`even if “treating cancer” was limiting, the term does not require more effectiveness
`
`than what is already required by “anti-tumor effective amount.” Pet., 13.
`
`
`
`3
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`
`Dr. Junghans explained a POSA would understand that “a decrease in the number of
`
`tumor cells” necessarily “‘reduc[es] the frequency or severity of at least one sign or
`
`symptom of a disease or disorder’” as tumor cells are a “‘sign or symptom of’
`
`cancer” (i.e., “treat[s]” as defined in the specification). Junghans, ¶55.
`
`Even if the Board finds that claim 1 requires some heightened level of
`
`therapeutic efficacy beyond “anti-tumor effect,” there is sufficient evidence a POSA
`
`would reasonably expect that outcome. E.g., Junghans, ¶177 (opining there was “a
`
`reasonable expectation of success that applying this dose [in the art] would have an
`
`anti-tumor effect because the dose range falls within the range of ‘therapeutically
`
`effective’ doses disclosed for other CD19-targeted CAR T cells.”), 174-76, 178-84,
`
`230-35; Pet., 35-38, 50. The POPR misleadingly relies on alleged failures of non-
`
`CD19 therapies to argue there was no reasonable expectation of success. E.g., Ex.
`
`2038 (anti-FR CAR); Ex. 2039 (anti-CAIX CAR). The POPR also ignores Petition
`
`art that supports a reasonable expectation of success for CD19 CARs: Jensen (Ex.
`
`1007), Milone (Ex. 1008), and Dr. Junghans’ reasons that a POSA would understand
`
`CART-19 ClinicalTrials.gov to be descriptive of the Campana CAR. Pet., 19;
`
`Junghans, ¶¶157-64.
`
`B.
`“Anti-Tumor Effective Amount”
`Notably, PO does not dispute that “anti-tumor effective amount” is necessarily
`
`satisfied by a dosage of 104 to 109 cells per kg, as recited in a dependent claim. Pet.,
`
`
`
`4
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`
`13-15. And PO has not rebutted Petitioner’s evidence that using such a dosage would
`
`have been obvious. E.g., id., 30-33; Junghans, ¶¶155-64. It is thus unnecessary for
`
`the Board to address PO’s argument that “anti-tumor effective amount” requires a
`
`therapeutic effect more than “a decrease in the number of tumor cells.”
`
`III. The Board Should Not Deny Institution Under Section 325(d)
`Biocon Pharma v. Novartis Pharms., IPR2020-01263, Paper 12 (P.T.A.B.
`
`Feb. 16, 2021), does not hold that discretionary denial is appropriate whenever a
`
`subset of the Petition’s art is buried in a multitude of references (here, 174) cited in
`
`an IDS. In Biocon, the relevant art was extensively addressed during examination
`
`and not merely listed on an IDS. Biocon, 8-9 (agreeing that “Petitioner’s grounds of
`
`unpatentability are based on the same arguments that led the Examiner to twice reject
`
`the claims of the application ….”). Here, in contrast, none of the art in Ground 1 was
`
`the basis for rejection or discussed at all during prosecution. Pet., 69.
`
`Even after Advanced Bionics, the Board has consistently held that citation of
`
`the petition’s prior art in an IDS is, by itself, insufficient to avoid institution where,
`
`as here, the art was not discussed during examination. Pet., 70 (citing Trend Micro
`
`Inc. v. CUPP Computing AS, IPR2021-00813, Paper 7 at 21-23 (P.T.A.B. Oct. 25,
`
`2021)); Samsung Electronics Co. v. Evolved Wireless LLC, IPR2021-00943, Paper
`
`9 at 11-12 (P.T.A.B. Dec. 1, 2021); Satco Products Inc. v. The Regents of the Univ.
`
`of California, IPR2021-00662, Paper 13 at 25 (P.T.A.B. Nov. 8, 2021).
`
`
`
`5
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`/
`
`Respectfully submitted,
`
`
`/Yite John Lu
`Yite John Lu (Reg. No. 63,158)
`jlu@milbank.com
`Tel. (424) 386-4318
`
`Counsel for Petitioner
`
`Gary N. Frischling (Reg. No. 35,515)
`gfrischling@milbank.com
`Tel. (424) 386-4316
`
`David I. Gindler (to be pro hac vice)
`dgindler@milbank.com
`Tel. (424) 386-4313
`
`Milbank LLP
`2029 Century Park East, 33rd Floor
`Los Angeles, CA 91167
`Fax. (213) 629-5063
`
`Backup Counsel for Petitioner
`
`
`
`
`DATED: August 12, 2022
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`6
`
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`Certificate of Service
`
`I hereby certify, pursuant to 37 C.F.R. Sections 42.6 and 42.105, that a
`complete copy of the attached Petitioners’ Reply to Patent Owner’s
`Preliminary Response, is being served on the twelfth day of August, the same
`day as the filing of the above-identified document in the United States Patent and
`Trademark Office/Patent Trial and Appeal Board, upon the patent owner by
`serving via electronic mail to the following:
`Counsel for Patent Owner
`Backup Counsel for Real Party in
`Brian R. Laundry (Reg. No. 62, 074)
`Interest and Licensee Novartis Pharma
`Saul Ewing Arnstein & Lehr LLP
`AG
`131 Dartmouth St, Ste 501
`Jessamyn S. Berniker (Reg. No. 72,328)
`Boston, MA 02116
`David M. Krinsky (Reg. No. 72,339)
`Tel. (617) 912-0969
`Thomas S. Fletcher (Reg. No. 72,383)
`Williams & Connolly LLP
`Brian.landry@saul.com
`680 Maine Ave SW
`
`Washington, DC 20024
`Backup Counsel for Patent Owner
`Tel. (202) 434-5000
`Kathryn Doyle (Reg. No. 36,317)
`jberniker@wc.com
`Saul Ewing Arnstein & Lehr LLP
`drinsky@wc.com
`1500 Market St, 38th Floor
`tfletcher@wc.com
`Philadelphia, PA 19102
`Tel. (215) 972-7734
`Kathryn.doyle@saul.com
`
`Alireza Behrooz (Reg. No. 60,882)
`Saul Ewing Arnstein & Lehr LLP
`1919 Pennsylvania Ave, N.W.,
`Ste 550
`Washington, DC 20006-3434
`Tel. (202) 295-6687
`Alireza.behrooz@saul.com
`
`
`
`
`7
`
`
`
`
`
`
`
`DATED: August 12, 2022
`
`
`
`
`IPR2022-00853
`Patent No. 9,464,140
`
`/
`
`/Yite John Lu
`Yite John Lu (Reg. No. 63,158)
`Milbank LLP
`2029 Century Park East, 33rd Floor
`Los Angeles, CA 91167
`Tel. (424) 386-4318
`Fax. (213) 629-5063
`jlu@milbank.com
`Counsel for Petitioner
`
`
`
`8
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`