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`UNITED STATES PATENT AND TRADEMARK OFFICE
`______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________
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`MILTENYI BIOMEDICINE GmbH and MILTENYI BIOTEC INC.,
`Petitioners,
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`v.
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`TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA,
`Patent Owner.
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`_________________________________________________
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`Case IPR 2022-00853
`Patent 9,464,140
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`__________________
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`SURREPLY OF PATENT OWNER
`TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
`AND REAL PARTY IN INTEREST NOVARTIS PHARMA AG
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`1
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`TABLE OF CONTENTS
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`I. Porter Is Not The Work Of “Another” ................................................................ 1
`II. Miltenyi’s “Claim Construction” Arguments Are Meritless ............................... 3
`III. The Board Should Deny Institution Under § 325(d) ........................................ 5
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`1
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`TABLE OF AUTHORITIES
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`CASES
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`Eli Lilly v. Teva Pharms.,
`8 F.4th 1331 (Fed. Cir. 2021) ........................................................................... 3, 4
`In re Katz,
`687 F.2d 450 (C.C.P.A. 1982) .......................................................................... 1, 2
`Riverwood Int’l v. R.A. Jones,
`324 F.3d 1346 (Fed. Cir. 2003) ............................................................................ 2
`Biocon Pharma v. Novartis Pharms.,
`IPR2020-01263, Paper 12 (PTAB Feb. 16, 2021) ................................................ 5
`Fresenius v. Chugai,
`IPR2021-01288, Paper 30 (PTAB Feb. 23, 2022) ................................................ 1
`Nelson Products, Inc. v. BAL Seal Engineering, Inc.,
`IPR2014-00573, Paper 9 (PTAB Sep. 29, 2014) .................................................. 3
`Watson Labs. Inc., v. United Therapeutics Corp.,
`IPR2017-01621, Paper 10 (PTAB Jan. 11, 2018) ................................................ 3
`Sanofi-Aventis U.S. LLC v. Immunex Corp.,
`IPR2017-01879, Paper 19 (PTAB Feb. 15, 2018) ................................................ 3
`Pfizer v. Genentech,
`IPR2018-00373, Paper 12 (Aug. 2, 2018) ............................................................ 1
`R.J. Reynolds v. Altria,
`IPR2021-00793, Paper 7 (PTAB Oct. 27, 2021) .................................................. 1
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`2
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`Miltenyi’s Reply misconstrues the relevant legal standards and ignores key
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`arguments Patent Owner made in its POPR. Institution should be denied.
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`I.
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`Porter Is Not The Work Of “Another”
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`Miltenyi does not dispute that the Porter clinical trial is the same one reported
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`in the patent: the seminal study demonstrating, after years of failure, that CAR-T
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`therapy would work as a cancer treatment. Instead, Miltenyi suggests that institution
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`should be granted despite proof that Porter is not “by another” because declarations
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`“attempting to disqualify prior art in [POPRs]” should not defeat institution. Reply
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`2. But the Board has denied institution on the basis of declarations, like the one here,
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`showing that alleged prior art is not the “work of another,” In re Katz, 687 F.2d 450,
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`454 (C.C.P.A. 1982). E.g., R.J. Reynolds v. Altria, IPR2021-00793, Paper 7, at 5–7
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`(PTAB Oct. 27, 2021) (denying institution based on author declaration and evidence
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`of “a common inventive entity”); cf. Fresenius v. Chugai, IPR2021-01288, Paper 30
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`at 41–42 (PTAB Feb. 23, 2022) (considering antedation declaration at institution);
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`Pfizer v. Genentech, IPR2018-00373, Paper 12, at 15 (Aug. 2, 2018) (denying
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`institution where Examiner had considered attribution declaration).
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`Miltenyi’s alleged “factual questions” are illusory. Reply 2. As in R.J.
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`Reynolds, the documentary evidence here indicates common inventorship even
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`before considering Dr. Bagg’s declaration. The named inventors are all co-authors
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`of Porter. And on their face, the patent and Porter plainly disclose the very same
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`1
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`clinical trial results. Compare, e.g., Ex. 1001 fig.12 D with Ex. 1012 at 5 (depicting
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`identical patient CT scans).
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`Miltenyi disputes none of this, and is constrained to flyspeck Dr. Bagg’s role.
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`Contrary to Miltenyi’s assertions, both Porter and Dr. Bagg’s declaration
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`consistently indicate that Dr. Bagg analyzed samples, determined laboratory results
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`indicating remission, and passed that information on to the inventors. Ex. 2044 at
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`3; Ex. 1013 at 36, 37; Reply 1–2. In fact, the assays that Miltenyi touts were
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`described in both Porter and the patent. Compare Ex. 1013, 36 (describing MRD
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`assessments, cited at Reply 1), with Ex. 1001, 57:18–26. Dr. Bagg’s contribution—
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`performing “assays and testing” at the inventors’ instruction, Ex. 2044 at 2–3—may
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`warrant discretionary co-authorship of academic papers, but does not constitute legal
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`inventorship; he is not part of the “common inventive entity” that conceived the
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`work reported in both Porter and the patent. Katz at 455; Riverwood Int’l v. R.A.
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`Jones, 324 F.3d 1346, 1356 (Fed. Cir. 2003). There also is no factual dispute
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`because Dr. Bagg did not contribute “the portions of the reference relied on as prior
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`art.” Riverwood, 324 F.3d at 1356. Dr. Bagg’s assays were only one factor in Dr.
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`Porter’s “clinical determination of remission.” Ex. 2044 at 3. Miltenyi equates that
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`determination, not the assays, to the “antitumor effect,” and does not reference the
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`assay results in its Petition. POPR 42; compare Pet. 65–69 with Ex. 2044 ¶¶ 7–13.
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`Miltenyi’s cases involve much closer questions. In Watson, the Board found
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`that the declarations “leave some ambiguity as to whether and to what extent” the
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`relevant portions of the reference were the work of the named inventors, who (unlike
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`here) were not authors of the reference. IPR2017-01621, Paper 10, at 13 (PTAB
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`Jan. 11, 2018). In Nelson Products, the only evidence of who invented large swathes
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`of the cited art, including the cited figure, was the co-author’s say-so, and “nothing
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`further.” IPR2014-00573, Paper 9, at 11 (PTAB Sep. 29, 2014). And in Sanofi-
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`Aventis, the prior art was a publication of a patent application naming a single
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`inventor who was not named as an inventor of the challenged patent. IPR2017-
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`01879, Paper 19, at 13–14 (PTAB Feb. 15, 2018). In each case there was a genuine
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`factual question about who contributed the relevant material. Here, there is no
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`“reasonable likelihood” that the portions of Porter cited by Miltenyi are prior art.
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`II. Miltenyi’s “Claim Construction” Arguments Are Meritless
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`The Preamble. The POPR explained why the preamble limitation “treating
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`cancer” is limiting under Eli Lilly v. Teva Pharms., 8 F.4th 1331 (Fed. Cir. 2021).
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`Miltenyi wrongly seeks to distinguish Lilly by arguing that the claims here contain
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`another term—“anti-tumor effective amount”—that “provides sufficient guidance
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`for limiting effectiveness,” but then attempts to strip that term of meaning as well.
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`But Miltenyi cites its Petition, not Lilly, for this distinction because this supposed
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`rule is Miltenyi’s invention. In fact, this case is on all fours with Lilly. As in Lilly,
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`the preamble “embod[ies] the essence of the claimed invention” by stating “the
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`intentional purpose for which the methods must be performed.” Lilly at 1340–42.
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`And as in Lilly, the specification confirms that the preamble “is central to the
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`invention[],” as “reflected in the extensive discussions” of treating cancer in “every
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`section of the patent[’s] written description.” Lilly at 1342; POPR 17–19. Treating
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`cancer using the claimed method is the invention in the ’140 patent.
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`Miltenyi tries to walk back its concession that the patent defines “treatment”
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`as “reducing the frequency or severity of at least one sign or symptom of a disease
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`or disorder.” Reply 4; Pet. 13; Ex. 1001 at 13:53–54; 18:18–20. But Miltenyi cannot
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`show that killing a handful of cancer cells reduces any “sign or symptom” or is what
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`the patent—which repeatedly discloses impressive, visible clinical results such as
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`complete remissions—is talking about. Ex. 1001 at 52:61–53:42, 61:43–62.
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`Finally, Miltenyi reiterates its flawed argument that the doses in an early-stage
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`trial, unrelated to Campana, somehow provide a reasonable expectation of success.
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`Reply 4. The POPR already explained why this is wrong both legally and factually.
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`POPR 28–38. Miltenyi ignores this, other than a bizarre passing criticism of Patent
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`Owners’ citation of non-CD19 therapies, along with CD19 ones, to show that the
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`field was rife with failure and the patented invention represented a landmark success.
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`“Anti-Tumor Effective Amount.” In its reply, Miltenyi does not attempt to
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`dispute Patent Owner’s construction of this term, despite having sought a Reply
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`specifically for that purpose. Patent Owner’s construction is thus essentially
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`4
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`conceded. Miltenyi instead argues that Patent Owner’s construction “is necessarily
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`satisfied” by the dosages recited in dependent claims. Reply 4–5. But these are
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`separate limitations that must both be satisfied. Moreover, Miltenyi must prove a
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`reasonable expectation of success. As explained in the POPR and not refuted here,
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`Miltenyi cannot demonstrate that the POSA would have reasonably expected that
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`any dosage—including 104 to 109 cells—would be an “effective amount,” given the
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`prior art. POPR 23–41. Miltenyi ignores this critical defect in its argument.
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`III. The Board Should Deny Institution Under § 325(d)
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`The POPR explained how the mountain of art Miltenyi piles up in four-
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`reference obviousness combinations—or art substantially similar to it—was before
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`the Examiner and, at minimum, listed in an IDS initialed by the Examiner. POPR
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`44–52. That warrants discretionary denial under Biocon Pharma v. Novartis
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`Pharms., IPR2020-01263, Paper 12 (PTAB Feb. 16, 2021). The Board in Biocon
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`expressly stated that it “need not reach” the purported distinction Miltenyi relies
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`on—that the grounds were “based on the same arguments” that led to rejection. Id.
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`at 9 n.4. That the Examiner here did not expressly discuss the precise combination
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`of multiple (cumulative) references Miltenyi now cites does not warrant institution.
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`5
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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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`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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`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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`Certification of Service Under 37 C.F.R. § 42.6(e)(4)
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`The undersigned hereby certifies that Patent Owner’s Surreply was served in its
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`entirety by filing through the Patent Trial and Appeal Board End to End (PTAB
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`E2E), as well as providing a courtesy copy via e-mail to the following attorneys of
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`record for Petitioners listed below:
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`Yite John Lu
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`Gary Frischling
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`jlu@milbank.com
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`gfrischling@milbank.com
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`Date: August 19, 2022
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`/Brian R. Landry/
`By:
`Reg. No. 62,074
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