UNITED STATES PATENT AND TRADEMARK OFFICE
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`———————————
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`———————————
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`MILTENYI BIOMEDICINE GmbH and MILTENYI BIOTEC INC.,
`Petitioner
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`v.
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`THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA,
`Patent Owner
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`———————————
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`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
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`PATENT OWNER’S SURREPLY TO REQUEST FOR REHEARING
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`(authorized by Order of November 23, 2022, Ex. 3004)
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`———————————
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`———————————
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`MILTENYI BIOMEDICINE GmbH and MILTENYI BIOTEC INC.,
`Petitioner
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`v.
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`THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA,
`Patent Owner
`
`
`———————————
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`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
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`———————————
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`PATENT OWNER’S SURREPLY TO REQUEST FOR REHEARING
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`(authorized by Order of November 23, 2022, Ex. 3004)
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`TABLE OF CONTENTS
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`TABLE OF AUTHORITIES .................................................................................... ii
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`I. Miltenyi Cannot Erase Decades of Failures .................................................... 1
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`II. Miltenyi Dismisses the Reasonable Expectation of Success Requirement ..... 3
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`III. The Board Did Not Abuse Its Discretion In Discretionarily Denying
`Institution Under Section 325(d) ..................................................................... 4
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`i
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`TABLE OF AUTHORITIES
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`CASES
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d
`1339 (Fed. Cir. 2003) ............................................................................................ 1
`Genzyme Therapeutic Prod. Ltd. P’ship. v. Biomarin Pharm. Inc., 825 F.3d
`1360 (Fed. Cir. 2016) ........................................................................................ 1, 2
`Novartis v. West-Ward., 923 F.3d 1051 (Fed. Cir. 2019) ...................................... 2, 4
`OSI Pharms., LLC v. Apotex Inc., 939 F.3d 1375 (Fed. Cir. 2019) .......................... 2
`Teva Pharms. Int’l GmbH v. Eli Lilly & Co., 8 F.4th 1349 (Fed. Cir. 2021) ........ 2, 4
`Teva Pharms. USA, Inc. v. Corcept Therapeutics, Inc., 18 F.4th 1377 (Fed.
`Cir. 2021) .............................................................................................................. 4
`Univ. of Strathclyde v. Clear-Vu Lighting LLC, 17 F.4th 155 (Fed. Cir.
`2021) ..................................................................................................................... 1
`37 C.F.R. § 42.71(d) .............................................................................................. 4, 5
`35 U.S.C. § 325(d) ................................................................................................. 4, 5
`Biocon v. Novartis, IPR2020-01263, Paper 12 (PTAB Feb. 16, 2021) ..................... 5
`Spectrum Solutions LLC v. DNA Genotek Inc., IPR2022-00134, Paper 7
`(PTAB June 6, 2022) ............................................................................................ 5
`Target Corp. v. Proxicom Wireless LLC, IPR2020-00980, Paper 11 (PTAB
`Dec. 4, 2020) ......................................................................................................... 5
`Telebrands v. Tinnus Enter’s., PGR2017-00040, Paper 10 (PTAB Feb. 7,
`2018) ..................................................................................................................... 5
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`ii
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`Miltenyi’s Reply confirms that it is not the non-institution decision that is an
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`outlier, but Miltenyi’s own Petition, which seeks to relitigate questions the Board
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`neither misapprehended nor overlooked and barely even pays lip service to the
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`high standard for rehearing. The Board’s decision was correct and firmly
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`grounded in Miltenyi’s failure to demonstrate a reasonable expectation of success
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`and in its reliance on art that the Examiner considered in great detail.
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`I. Miltenyi Cannot Erase Decades of Failures.
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`Miltenyi’s argument is premised on a suggestion that the Federal Circuit
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`tacitly created a per se rule in Genzyme that reasonable expectation of success is
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`satisfied where there is some “successful in-vitro data and a proposed clinical
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`trial.” Reply 3. But there is no such rule. As the cases demonstrate, whether there
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`is a reasonable expectation of success depends on the particular facts of the case.
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`Miltenyi cannot point to any principle the Board overlooked warranting
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`correction on rehearing. Miltenyi made the same argument in its Petition, and the
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`Board correctly rejected it, noting that “the inherent unpredictability of the field
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`and the history of failures of similar technology” meant that Miltenyi had not
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`established a reasonable expectation of success here. Paper 11 at 41.
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`The Board aptly focused on the unpredictability and history of failures in the
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`field, because the cases repeatedly instruct that those factors critically undermine a
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`reasonable expectation of success. Boehringer, 320 F.3d at 1354; Strathclyde, 17
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`1
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`F.4th at 164; Novartis v. West-Ward., 923 F.3d 1051, 1060-61, 1053-54 (Fed. Cir.
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`2019) (noting 70% failure rate for cancer drugs in phase II); Lilly, 8 F.4th at 1358;
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`OSI, 939 F.3d at 1383. Miltenyi has no answer for that or for the facts here.
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`Miltenyi is silent on Patent Owner’s mountain of evidence showing decades of
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`failures, including a more than 84% clinical trial failure rate, and routine
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`expressions of hopelessness in the field. POPR 4-7, 23-28; Paper 11 at 41.
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`Genzyme does not compel a contrary result. The Genzyme invention was a
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`modified enzyme used in enzyme replacement therapy. 825 F.3d at 1363-64.
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`While the natural enzyme was not successful because it accumulated in the liver
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`instead of the muscle tissue where it was needed, the art taught that the claimed
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`modified enzyme would solve this problem because it “was effectively taken up by
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`muscle cells.” Id. at 1373. On that record, where there was neither unpredictability
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`nor a reason to expect failure of the modified enzyme, the Board found (and the
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`Federal Circuit affirmed) a reasonable expectation of success. Id.
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` That stands in stark contrast with the history of clinical failures of CAR-T
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`trials here. As in OSI, the invention here involves the “highly unpredictable” field
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`of cancer treatment, where in vitro data suggesting anti-cancer activity frequently
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`fails to work clinically. Paper 11 at 40 (quoting OSI, 939 F.3d at 1377). The
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`Board appreciated that the in vitro data here are arguably stronger than those in
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`OSI, where data showed enzyme inhibition but not specifically the ability to kill
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`2
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`NSCLC cells. Id. at 41. Even interpreting the data this way, there was no error—
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`let alone anything the Board misapprehended or overlooked—in the Board’s well-
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`reasoned conclusion on reasonable expectation of success. The art decidedly did
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`not teach that “there was little left to do but to confirm that the strategy suggested”
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`by the prior art would work. Instead, it taught that CAR-T therapy “was way out
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`there,” Ex. 2004 at 1, and “had scarcely worked in cancer, anywhere in the world.”
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`Ex. 2001 at 2. “The whole idea was starting to seem like a bust.” Id.
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`II. Miltenyi Dismisses the Reasonable Expectation of Success Requirement.
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`Miltenyi continues to try to conjure an inconsistency with the decision in the
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`composition case, IPR2022-00855. But the Reply demonstrates Miltenyi’s sleight
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`of hand: it seeks to avoid the need to show a reasonable expectation of success in
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`treating cancer by asserting that “a POSA expected administration to patients.”
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`Reply 4. There is no basis, and Miltenyi presents no authority, for its suggestion
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`that this is sufficient to show a reasonable expectation of success of a method of
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`treatment. There is no inconsistency with the Board’s composition decision, which
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`focused on the expectation of success in “making the pharmaceutical
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`composition.” IPR2022-00855, Paper 10 at 26-27 (emphasis added).
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`Miltenyi suggests that proof of a reasonable expectation of success for a
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`method of treatment claim is unnecessary whenever a POSA would have been
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`motivated and able to make a composition, on the theory that effectiveness is the
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`3
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`“inherent result of administering” the composition. Reply 4. Setting aside whether
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`the Board actually found “that a POSA expected administration to patients,” Reply
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`4, Miltenyi’s assertion is not the law, and Miltenyi cites no authority to establish
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`that it is. In fact, the Federal Circuit has held the exact opposite, upholding the
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`non-obviousness of treatment methods even where there was a motivation to make
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`and administer the compositions. Novartis, 923 F.3d at 1060-61; Lilly, 8 F.4th at
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`1337-39, 1344-45. Proving a reasonable expectation of success is mandatory and
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`separate from motivation, and it cannot be omitted or side-stepped. E.g., Teva v.
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`Corcept, 18 F.4th at 1383. That is fatal to Miltenyi’s case.
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`III. The Board Did Not Abuse Its Discretion In Discretionarily Denying
`Institution Under Section 325(d).
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`Miltenyi seeks to revisit the Board’s discretionary decision not to institute on
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`Ground 3 under 35 U.S.C. § 325(d). On rehearing, the question for the Board is
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`whether it overlooked or misapprehended some dispositive facts or legal principles
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`such that its prior decision not to institute was an abuse of discretion. 37 C.F.R.
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`§ 42.71(d). Miltenyi does not come close to demonstrating such an error.
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`Again, Miltenyi tries to invent a new rule—this time that the Board may
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`only deny institution under § 325(d) where the reference was specifically
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`distinguished during prosecution on grounds applicable to the instant claims.
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`Reply 4-5. There is no such rule. Nor is it correct that “knowledge of a reference
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`is not sufficient for discretionary denial.” Reply at 4. The Board has declined to
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`4
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`institute when the reference has not been discussed explicitly at all, merely
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`“considered.” Biocon v. Novartis, IPR2020-01263, Paper 12 at 9 (PTAB Feb. 16,
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`2021); see also Telebrands v. Tinnus Enters., PGR2017-00040, Paper 10 at 14-15
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`(PTAB Feb. 7, 2018).
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`Nor do Miltenyi’s two supposedly “on-point” cases, Reply at 4, purport to
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`establish Miltenyi’s (or any) governing rule regarding § 325(d). In Target, there
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`was no evidence that a different, new Examiner had considered the reference.
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`Miltenyi posits that the Examiner was “presumed to know” of the reference, Reply
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`5, but this pales in comparison to the facts here where the Examiner had discussed
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`Milone extensively in several earlier prosecutions and expressly considered it
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`again in this very application, Ex. 2026 at 7. It is implausible to suggest that he
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`did not consider its implications. And Miltenyi does not even try to address the
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`distinction of Spectrum, which involved a strong showing of anticipation and a
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`“material error” by the examiner. Resp. at 15.
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`Miltenyi cannot and does not point to anything the Board—or the Examiner
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`for that matter—overlooked or misunderstood. Milone was substantively
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`addressed repeatedly by the Examiner. And he was well aware of how the ’140
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`patent claims differed compared to those of the ’622 application, having examined
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`their differences for purposes of a double-patenting rejection. Ex. 1021 at 8.
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`None of Miltenyi’s arguments come close to satisfying 37 C.F.R. § 42.71(d).
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`5
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`Dated: December 15, 2022
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`Respectfully submitted,
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`By:
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`/ Brian R. Landry/
`Brian Landry (Reg. No. 62,074)
`SAUL EWING ARNSTEIN & LEHR LLP
`131 Dartmouth Street, Suite 501
`Boston, MA 02116
`Tel: (617) 912-0969
`brian.landry@saul.com
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`Counsel for Patent Owner
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`Kathryn Doyle (Reg. No. 36,317)
`SAUL EWING ARNSTEIN & LEHR
`LLP
`Centre Square West
`1500 Market Street, 38th Floor
`Philadelphia, PA 19102
`Tel: (215) 972-7734
`kathryn.doyle@saul.com
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`Alireza Behrooz (Reg. No. 60,882)
`SAUL EWING ARNSTEIN & LEHR
`LLP
`1919 Pennsylvania Avenue, N.W.,
`Suite 550
`Washington, DC 20006-3434
`Tel: (202) 295-6687
`alireza.behrooz@saul.com
`Backup Counsel for Patent Owner
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`Jessamyn S. Berniker (Reg. No.
`72,328)
`David M. Krinsky (Reg. No. 72,339)
`Thomas S. Fletcher (Reg. No.
`72,383)
`WILLIAMS & CONNOLLY LLP
`680 Maine Avenue SW
`Washington, DC 20024
`Tel: (202) 434-5000
`jberniker@wc.com
`dkrinsky@wc.com
`tfletcher@wc.com
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`Backup Counsel for Real Party in
`Interest and Licensee Novartis
`Pharma AG
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`Certification of Service Under 37 C.F.R. § 42.6(e)(4)
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`The undersigned hereby certifies that Patent Owner’s Response to Petitioner’s
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`Request for Rehearing of Institution Decision was served in its entirety by filing
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`through the Patent Trial and Appeal Case Tracking System (P-TACTS), as well as
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`providing a courtesy copy via e-mail to the following attorneys of record for
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`Petitioners listed below:
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`Yite John Lu
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`Gary N. Frischling
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`Date: December 15, 2022
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`PTABDocketL2Y7@orrick.com
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`PTABDocketG2F1@orrick.com
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`By: /Brian R. Landry/
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`Reg. No. 62,074
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`7
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