Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 1 of 38 PageID #: 10365
`FILED UNDER SEAL PURSUANT TO PROTECTIVE ORDER
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`
`
`IN THE UNITED STATES DISTRICT COURT
`EASTERN DISTRICT OF TEXAS
`MARSHALL DIVISION
`
`Civil Action No. 2:20-CV-00337-JRG
`
`FILED UNDER SEAL
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`SEAGEN INC.,
`
`v.
`
`Plaintiff,
`
`DAIICHI SANKYO CO., LTD.,
`
`Defendant,
`
`ASTRAZENECA PHARMACEUTICALS LP, and
`ASTRAZENECA UK LTD,
`
`
`Intervenor-Defendants.
`
`SEAGEN’S OPPOSITION TO DSC’S MOTION FOR SUMMARY JUDGMENT
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`sf-4659064
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`

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`Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 2 of 38 PageID #: 10366
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`TABLE OF CONTENTS
`
`
`PAGE
`
`
`I.
`
`II.
`
`INTRODUCTION ............................................................................................................. 1
`
`STATEMENT OF ISSUES TO BE DECIDED BY THE COURT .................................. 2
`
`III.
`
`BACKGROUND ............................................................................................................... 2
`
`A.
`
`B.
`
`C.
`
`Antibody-Drug Conjugates (ADCs) ...................................................................... 2
`
`History of Seagen’s ADC Technology .................................................................. 3
`
`The ’039 Patent ...................................................................................................... 5
`
`IV.
`
`LEGAL STANDARDS ..................................................................................................... 6
`
`A.
`
`Summary Judgment ............................................................................................... 6
`
`B. Written Description ................................................................................................ 7
`
`V.
`
`ARGUMENT ..................................................................................................................... 8
`
`A.
`
`There Are Genuine Issues of Material Fact in Dispute Regarding Whether
`the Disclosure of the Priority Applications Meets the Written Description
`Requirement ........................................................................................................... 9
`
`1.
`
`2.
`
`The Priority Applications Disclose a Precise Chemical Formula
`and Narrow the Options from Which the Substituents Could Be
`Selected ...................................................................................................... 9
`
`The Applicable Law Does Not Dictate the Result Urged By
`Defendants ............................................................................................... 13
`
`B.
`
`There Are Genuine Issues of Material Fact in Dispute Regarding Whether
`the Priority Applications Provide Blaze Marks Guiding a Person of
`Ordinary Skill to the Claimed Tetrapeptide ......................................................... 16
`
`1.
`
`2.
`
`3.
`
`The Priority Applications Guide a Person of Ordinary Skill
`Toward the Claimed Tetrapeptides .......................................................... 16
`
`The Prior Art Disclosed Tetrapeptide Sequences with Gly/Phe .............. 19
`
`Reliance on Prior Art in a Written Description Analysis Is Not
`Improper ................................................................................................... 21
`
`C.
`
`Defendants’ Additional Arguments Are Unpersuasive ....................................... 22
`
`1.
`
`2.
`
`Actual Reduction to Practice of the Claimed Tetrapeptides Is
`Legally Irrelevant ..................................................................................... 22
`
`The Inventors’ Alleged Inability to Identify “Blaze Marks” Is Not
`Dispositive, and Is Mischaracterized by Defendants ............................... 23
`
`
`
`i
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`Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 3 of 38 PageID #: 10367
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`TABLE OF CONTENTS
`(CONTINUED)
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`PAGE
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`
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`3.
`
`4.
`
`The Blaze Marks Need Not Point Toward the Exact Claimed
`Subgenus .................................................................................................. 28
`
`Defendants’ Commentary on Seagen’s Prosecution Strategy Is
`Wholly Irrelevant to Written Description ................................................ 29
`
`VI.
`
`CONCLUSION ................................................................................................................ 30
`
`
`
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`TABLE OF AUTHORITIES
`
`
`PAGE(S)
`
`
`
`Cases
`
`Abbott Biotechnology Ltd. v. Centocor Ortho Biotech, Inc.,
`35 F. Supp. 3d 163 (D. Mass. 2014) ..........................................................................................7
`
`All Dental Prodx, LLC v. Advantage Dental Prods., Inc.,
`309 F.3d 774 (Fed. Cir. 2002)..................................................................................................22
`
`Allergan, Inc. v. Sandoz Inc.,
`796 F.3d 1293 (Fed. Cir. 2015)............................................................................................7, 23
`
`Allure Energy, Inc. v. Nest Labs, Inc.,
`No. 9-13-CV-102, 2015 WL 11110607 (E.D. Tex. May 11, 2015) ................................ passim
`
`Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (2010) .......................................................................................................7, 8, 23
`
`Boston Sci. Corp. v. Johnson & Johnson,
`647 F.3d 1353 (Fed. Cir. 2011)................................................................................7, 22, 28, 29
`
`Burns v. Bd. of Cnty. Comm’rs of Jackson Cnty.,
`330 F.3d 1275 (10th Cir. 2003) ...............................................................................................27
`
`Capon v. Eshhar,
`418 F.3d 1349 (Fed. Cir. 2005)..................................................................................................8
`
`Devon Energy Corp. v. Westacott,
`C.A. No. H-09-1689, 2011 WL 1157334 (S.D. Tex. Mar. 24, 2011) ......................................27
`
`In re Driscoll,
`562 F.2d 1245 (C.C.P.A. 1977) .....................................................................................8, 13, 14
`
`Enzo Biochem, Inc. v. Gen–Probe Inc.,
`323 F.3d 956 (Fed. Cir. 2002)..................................................................................................23
`
`Falkner v. Inglis,
`448 F.3d 1357 (Fed. Cir. 2006)................................................................................................22
`
`Fujikawa v. Wattanasin,
`93 F.3d 1559 (Fed. Cir. 1996)............................................................................................15, 28
`
`
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`iii
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`Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 5 of 38 PageID #: 10369
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`TABLE OF AUTHORITIES
`(CONTINUED)
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`GEODynamics, Inc. v. Dynaenergetics US,
`No. 2:17-CV-00371-RSP, 2018 WL 4680516 (E.D. Tex. Sept. 27, 2018) .............................24
`
`PAGE(S)
`
`GeoTag, Inc. v. Frontier Commc’ns Corp.,
`No. 2:10-CV-00265-JRG, 2014 WL 129835 (E.D. Tex. Jan. 14, 2014)
`(Gilstrap, J.) ...............................................................................................................................6
`
`Gonzalez v. Fresenius Medical Care North America,
`689 F.3d 470 (5th Cir. 2012) ...................................................................................................26
`
`Huawei Techs. Co. v. T-Mobile US, Inc.,
`No. 2:16-CV-00055-JRG-RSP, 2017 WL 5165606 (E.D. Tex. Oct. 15, 2017),
`report and recommendation adopted sub nom. Huawei Techs. Co. v. T-Mobile
`US, Inc., No. 2:16-CV-00055-JRG-RSP, 2017 WL 5157687 (E.D. Tex. Nov.
`7, 2017) ....................................................................................................................................27
`
`Idenix Pharms. LLC v. Gilead Scis. Inc.,
`941 F.3d 1149 (Fed. Cir. 2019)................................................................................................15
`
`Immunex Corp. v. Sandoz Inc.,
`964 F.3d 1049 (Fed. Cir. 2020), cert. denied, 141 S. Ct. 2623 (2021) ..............................22, 23
`
`Kingsdown Med. Consultants, Ltd. v. Hollister Inc.,
`863 F.2d 867 (Fed. Cir. 1988)..................................................................................................30
`
`Kowalski v. Mommy Gina Tuna Res.,
`574 F. Supp. 2d 1165 (D. Haw. 2008) .......................................................................................7
`
` Novartis Pharms. Corp. v. Accord Healthcare, Inc.,
`No. 2021-1070, 2022 U.S. App. LEXIS 58 (Fed. Cir. Jan. 3, 2022) .................................21, 29
`
`Novartis Pharms. Corp. v. Plexxikon Inc.,
`No. PGR2018-00069, Paper 16 (P.T.A.B. Jan. 16, 2019) ............................................... passim
`
`Novozymes A/S v. DuPont Nutrition Biosciences APS,
`723 F.3d 1336 (2013) ...............................................................................................................29
`
`Ricoh Co. v. Nashua Corp.,
`185 F.3d 884, No. 97-1344, 1999 WL 88969 (Fed. Cir. Feb. 18, 1999)
`(unpublished) ...........................................................................................................................30
`
`
`
`iv
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`Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 6 of 38 PageID #: 10370
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`TABLE OF AUTHORITIES
`(CONTINUED)
`
`
`In re Ruschig,
`379 F.2d 990 (C.C.P.A. 1967) ...........................................................................................14, 15
`
`PAGE(S)
`
`Steuben Foods, Inc. v. Oystar USA, Inc.,
`405 F. Supp. 3d 452 (W.D.N.Y. 2019) .................................................................................. 6-7
`
`Streck, Inc. v. Rsch. & Diagnostic Sys., Inc.,
`665 F.3d 1269 (Fed. Cir. 2012)................................................................................................23
`
`Texas Instruments Inc. v. U.S. Int’l Trade Comm’n,
`871 F.2d 1054 (Fed. Cir. 1989)................................................................................................30
`
`
`
`
`
`v
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`Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 7 of 38 PageID #: 10371
`FILED UNDER SEAL PURSUANT TO PROTECTIVE ORDER
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`Pursuant to the First Amended Docket Control Order (Dkt. 229), Seagen hereby responds
`
`to DSC’s Motion for Summary Judgment.
`
`I.
`
`INTRODUCTION
`
`Despite Defendants’ best attempt to paint written description in this case as an issue on
`
`which no facts are in dispute, it is clear that the parties’ experts starkly dispute how one of
`
`ordinary skill in the art would have evaluated the patent and its priority applications and the
`
`sufficiency of the priority applications’ disclosure. Seeking to elide that dispute, Defendants
`
`ignore a critical aspect of the claims: the recitation of a precise formula depicting the structure
`
`of the claimed compounds. Defendants also dismiss the exemplary tetrapeptides disclosed in the
`
`specification, and argue that they do not “point toward the claimed subgenus.”
`
`But as set forth in detail in her detailed report, Seagen’s expert, Dr. Bertozzi, opines that
`
`the priority applications disclose formulas that match the claimed structure, and that they
`
`specifically identify a tetrapeptide as one option for the linker. The amino acids called for in the
`
`claims are also disclosed in the applications. Defendants’ expert offers a different view, but this
`
`does not suffice to show that summary judgment is appropriate. Defendants’ argument regarding
`
`“blaze marks” also ignores a clear dispute in the expert evidence as to whether the priority
`
`applications are sufficient. Seagen’s expert properly took into account what was known in the
`
`art, as a central tenet of written description jurisprudence is that the disclosure is to be read from
`
`the perspective of a skilled artisan who is deemed to have knowledge of the prior art.
`
`Defendants’ other arguments are also unpersuasive. Defendants devote pages to recount
`
`testimony from Seagen’s inventors, who according to Defendants testified that they did not have
`
`possession of the invention because they had not actually reduced it to practice. But actual
`
`reduction to practice is not the relevant inquiry here, and Defendants’ reliance on the inventors’
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`testimony is misplaced. Nor is the inventors’ alleged inability to identify “blaze marks” in the
`
`priority applications dispositive here, and Defendants mischaracterize the inventors’ testimony in
`
`any event. Defendants’ made-up legal standard requiring that the blaze marks point to the exact
`
`claimed subgenus is also contrary to precedent and should be rejected.
`
`II.
`
`STATEMENT OF ISSUES TO BE DECIDED BY THE COURT
`
`Whether genuine factual disputes exist regarding whether the priority applications filed
`
`before the Ogitani reference provide adequate written description support for the asserted claims,
`
`such that summary judgment on the basis of anticipation is not appropriate.
`
`III. BACKGROUND
`
`A.
`
`Antibody-Drug Conjugates (ADCs)
`
`Antibody-drug conjugates, or “ADCs,” are drugs that combine a highly potent
`
`chemotherapeutic agent with a tumor-selective antibody by way of a linker unit. (Declaration of
`
`Carolyn Bertozzi, Ph.D. (“Bertozzi Decl.”) (attaching Bertozzi Decl. Ex. A, Rebuttal Expert
`
`Report of Carolyn Bertozzi (“Bertozzi”) at ¶ 38).) As shown below, an ADC has three basic
`
`components: an antibody, a toxic drug (or “payload”), and a “linker” between them that attaches
`
`the two. (Id.)
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`ADCs target cancer cells using the antibody component, and then deliver a drug payload
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`directly to the cancer cell. (Id. ¶ 39.) Unlike chemotherapy, where drugs are administered in an
`
`untargeted fashion, the toxic drug in an ADC gets delivered where it is needed. (Id.) This
`
`allows the use of more powerful chemotherapeutic drugs with fewer of the side effects and
`
`systemic toxicities than those drugs would otherwise cause to the body. (Id.)
`
`B.
`
`History of Seagen’s ADC Technology
`
`In the late 1980s and 1990s, Bristol-Myers-Squibb (“BMS”) conducted research into
`
`antibody-directed therapeutics, including antibody-drug conjugates. (Bertozzi ¶ 42.) BMS
`
`initially focused its ADC research on developing acid-cleavable linkers—linkers designed with
`
`the goal of maintaining stability in the neutral pH environment of the circulatory system but that
`
`degrade in the low-pH tumor microenvironment, resulting in the release of the drug payload unit.
`
`(Id.; Opp. Ex. 1, SGIEDTX00362049.) The linkers were used to attach doxorubicin, an anti-
`
`cancer drug. (Bertozzi ¶ 42.)
`
`BMS later expanded its focus to include development of protease-cleavable linkers, that
`
`is, linkers that are capable of being cut by enzymes within the target cell called “proteases.”
`
`(Bertozzi ¶ 43; Opp. Ex. 2, SGIEDTX00085997 (“Dubowchik Apr. 2002”).) In the 1990s, a
`
`particular protease, cathepsin B, was thought to be primarily responsible for this cleavage,
`
`because it is often highly expressed in tumors. (Bertozzi ¶ 43; Opp. Ex. 3,
`
`DSC_ENHERTU_00391635 at -635.) This work was spun out from BMS into the newly formed
`
`Seagen in the late 1990s. (Bertozzi ¶ 43.) The ’039 patent builds on this technology.
`
`Seagen’s ADC technology is the result of years of research and development by Seagen
`
`scientists. (Id. ¶ 44.) At its inception, Seagen exclusively licensed BMS’s ADC technology,
`
`including its protease-cleavable linker systems. (Id.) Dr. Peter Senter, formerly of BMS, also
`
`joined Seagen, and has been the head of chemistry at Seagen since he joined the company. (Id.)
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`At Dr. Senter’s direction, protease-cleavable linkers became a core focus of Seagen’s ADC
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`technology. (Id.) Seagen is now widely recognized as a pioneer in the development of protease-
`
`cleavable ADC linker systems. (Id.)
`
`Seagen’s research into protease-cleavable linkers was incorporated into Seagen’s
`
`contemporaneous patent filings. It was also published in the scientific literature in 2003 by Dr.
`
`Doronina, one of the named inventors, and colleagues. (Bertozzi ¶ 47; Opp. Ex. 4,
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`SGIEDTX00088427.) Her publication demonstrated the superiority of Seagen’s ADC
`
`technology compared to other technologies. (Id.) As explained by Dr. Senter, this technology
`
`allowed Seagen to create ADCs that “were more stable, led to specific cell killing activity and
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`regression of tumor in preclinical animal models, and displayed therapeutic indices as high as 60
`
`times compared to less stable acid-cleavable linkers.” (Bertozzi ¶ 47; Declaration of Peter Senter
`
`(“Senter Decl.”) (attaching Senter Decl. Ex. A, Witness Statement of Peter Senter at ¶ 13).)
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`The co-inventors’ work at Seagen with peptide libraries also expanded the list of amino
`
`acids for designing ADCs that would be intracellularly cleaved. Prior to 2003, cathepsin B was
`
`thought to be the primary protease responsible for intracellular cleavage. (See, e.g., Opp. Ex. 2,
`
`SGIEDTX00085997 at -997; Opp. Ex. 3, DSC_ENHERTU_00391635 at -635; see also Bertozzi
`
`¶¶ 68-69.) On this basis, the art discounted certain amino acid sequences, including
`
`tetrapeptides, for use in ADCs as they “were considered to have significant potential liabilities”
`
`due to slow drug release. (Id.) Nevertheless, after testing many different amino acid sequences,
`
`including di-, tri-, and tetrapeptides, the co-inventors discovered that they all cleaved
`
`intracellularly - even sequences that were not substrates for cathepsin B. (See, e.g., Opp. Ex. 5,
`
`described in the priority applications, taught that a vast array of amino acid sequences could be
`
` see also Bertozzi ¶¶ 70-79.) Their invention, as
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`used in protease-cleavable linker design. (Opp. Ex. 6, Kline Tr.
`
`; Opp.
`
`Ex. 7, Doronina Tr. at
`
` Opp. Ex. 20, Senter Tr.
`
`Opp. Ex. 8, Toki Tr.
`
`.)
`
`Seagen’s linker technology has been used to develop several FDA-approved ADCs for
`
`treating Hodgkin’s lymphoma and other CD30-positive lymphomas, B-cell lymphoma, advanced
`
`or metastatic urothelial cancer, and multiple myeloma, among other conditions. (Bertozzi ¶ 48.)
`
`Seagen received FDA approval for its first ADC, SGN-35 (now marketed as Adcetris®) in 2011.
`
`(Id.) Adcetris was the second ADC ever to receive approval, and the first approved ADC to
`
`employ a protease-cleavable linker. (Id.)
`
`Of the eleven ADCs currently approved by the FDA, at least five employ protease
`
`cleavable linkers. (Bertozzi ¶ 49.) Four of these are marketed by Seagen or its current
`
`collaborators. Of the remaining, one follows from a past collaboration between Seagen and
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`DSC: DS-8201 (marketed as Enhertu®), the drug that is the subject of this litigation. (Id.)
`
`C.
`
`The ’039 Patent
`
`The ’039 patent issued on October 20, 2020 from U.S. Patent Application No. 16/507,839
`
`(the “’839 application”), which was filed on July 10, 2019. (Opp. Ex. 9, SGIEDTX00003953 at
`
`-953 (“’039 Pat.”), front page.) The ’839 application is the last application filed in a series of
`
`seven divisional and continuation applications with the same specification filed between
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`November 5, 2004, and July 10, 2019, starting with U.S. Patent Application No. 10/983,340
`
`(Opp. Ex. 10, SGIEDTX00002840 at -840 (“’340 application”).) (Id.; Bertozzi ¶ 292.) The ’039
`
`patent claims priority to four provisional applications, with the earliest filed on November 6,
`
`2003. (Id.) The named inventors on the ’039 patent are Svetlana Doronina, Peter Senter, Brian
`
`Toki, and Toni Beth Kline. (Id.; Bertozzi ¶ 51.)
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`The ’039 patent discloses ADC technology that enables the delivery of chemotherapeutic
`
`drugs directly to cancer cells by linking them to antibodies. (Bertozzi ¶¶ 52-53.) The claims of
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`the ’039 patent are directed to ADCs that comprise a protease cleavable linker, and cover ADCs
`
`with linkers having a specific formula, shown below. (Id.)
`
`
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`In the formula, Ab is an antibody, S is a sulfur atom on a cysteine residue of the antibody, Ww is
`
`an amino acid unit, Y is a spacer unit, D is a drug moiety, y is 0, 1, or 2, and p ranges from 1 to
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`about 20. (’039 Pat. at Claim 1; Bertozzi ¶¶ 53-58.)
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`The amino acid unit Ww is protease-cleavable. (Bertozzi ¶ 55.) In the claims, it is a
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`tetrapeptide, meaning the unit has four amino acids. (Id.) Each amino acid has the structure
`
`shown above in which R19 is a hydrogen or benzyl group. (Id.) The amino acid glycine
`
`(abbreviated “G” or “Gly”) has hydrogen as the R19 group and the amino acid phenylalanine
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`(abbreviated “F” or “Phe”) has benzyl as the R19 group in this formula. (Id.) Thus, the Ww unit
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`in claim 1 is directed to a tetrapeptide in which each amino acid is glycine or phenylalanine.
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`(Id.)
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`IV.
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`LEGAL STANDARDS
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`A.
`
`Summary Judgment
`
`“Because of the presumption of validity that attaches to an issued patent, invalidity for
`
`lack of written description must be proven by clear and convincing evidence.” GeoTag, Inc. v.
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`Frontier Commc'ns Corp., No. 2:10-CV-00265-JRG, 2014 WL 129835, at *3 (E.D. Tex. Jan. 14,
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`2014) (Gilstrap, J.). “[C]ompliance with the written description is a question of fact on which
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`summary judgment is appropriate only in narrow circumstances.” Steuben Foods, Inc. v. Oystar
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`USA, Inc., 405 F. Supp. 3d 452, 464 (W.D.N.Y. 2019). There are only “rare instances in which
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`the facts firmly establish that a party has met or failed to meet the written-description
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`requirement.” Abbott Biotechnology Ltd. v. Centocor Ortho Biotech, Inc., 35 F. Supp. 3d 163,
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`178 (D. Mass. 2014). “Summary judgment on the written description requirement is not
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`appropriate if there is conflicting evidence as to what one of ordinary skill in the art would have
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`known.” Kowalski v. Mommy Gina Tuna Res., 574 F. Supp. 2d 1165, 1167 (D. Haw. 2008)
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`(citations omitted).
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`B. Written Description
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`The written description requirement provides that a patent’s disclosure should allow
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`persons of ordinary skill in the art “to recognize that [the inventor] invented what is claimed.”
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`Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (2010) (citation omitted). For genus
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`claims, this standard may be met either by describing “a representative number of species falling
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`within the scope of the genus,” or “structural features common to the members of the genus so
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`that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350.
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`“Because the specification is viewed from the perspective of one of skill, in some circumstances,
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`a patentee may rely on information that is ‘well-known in the art’ for purposes of meeting the
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`written description requirement.” Boston Sci. Corp. v. Johnson & Johnson, 647 F.3d 1353, 1366
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`(Fed. Cir. 2011).
`
`“Yet whatever the specific articulation, the test requires an objective inquiry into the four
`
`corners of the specification from the perspective of a person of ordinary skill in the art. Based on
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`that inquiry, the specification must describe an invention understandable to that skilled artisan
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`and show that the inventor actually invented the invention claimed.” Ariad, 598 F.3d at 1351.
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`Case 2:20-cv-00337-JRG Document 270 Filed 01/26/22 Page 14 of 38 PageID #: 10378
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`No rigid requirement exists that the disclosure contain either examples or an actual reduction to
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`practice. Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1308 (Fed. Cir. 2015). For generic
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`claims, a number of factors are considered for evaluating the adequacy of the disclosure,
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`including “the existing knowledge in the particular field, the extent and content of the prior art,
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`the maturity of the science or technology, [and] the predictability of the aspect at issue.” Ariad,
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`598 F.3d at 1363 (citations omitted).
`
`A genus can be adequately described by “a precise definition, such as by structure,
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`formula, chemical name, physical properties, or other properties, of species falling within the
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`genus sufficient to distinguish the genus from other materials.” Ariad, 598 F.3d at 1350; see also
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`Capon v. Eshhar, 418 F.3d 1349, 1356 (Fed. Cir. 2005) (rejecting requirement of “complete
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`nucleotide sequence of ‘at least one’ chimeric gene” as not grounded in precedent). This
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`formulation is especially apposite in the context of a chemical invention such as that claimed in
`
`the ’039 patent, where the claim recites a formula and the specification provides a defined set of
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`substituents from which claimed substituents are selected. Novartis Pharms. Corp. v. Plexxikon
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`Inc., No. PGR2018-00069, Paper 16 at 15-17 (P.T.A.B. Jan. 16, 2019); In re Driscoll, 562 F.2d
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`1245, 1249-50 (C.C.P.A. 1977).
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`V.
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`ARGUMENT
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`Defendants’ motion presents a single issue: have defendants shown that there are no
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`genuine issues of material fact as to whether the ’039 patent’s claim to priority to applications
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`filed before the Ogitani reference is supported by the written description in those applications?
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`If the patent can claim the benefit of a priority application, the ’039 patent claims are not
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`anticipated. Defendants argue that it is beyond genuine dispute that the priority applications lack
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`written description support for the tetrapeptide limitation of the claims, such that the ’039 patent
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`claims are not entitled to a filing date earlier than July 10, 2019. Defendants’ arguments fail.
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`A.
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`There Are Genuine Issues of Material Fact in Dispute Regarding Whether
`the Disclosure of the Priority Applications Meets the Written Description
`Requirement
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`Defendants argue that because the priority applications allegedly present a “laundry list”
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`of amino acids resulting in millions of potential compounds, they lack written description
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`support for the claims. (Mot. at 16-20.) While the textual disclosure of the priority applications
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`is not in dispute, whether that disclosure – which provides a specific formula, plus a list of
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`options from which to select the substituents, with examples that further narrow those choices –
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`is sufficient is indeed in dispute, as set forth in detail in Dr. Bertozzi’s reasoned report. (Bertozzi
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`¶¶ 295-305, 172-182.) “A disagreement between qualified experts is not grounds for summary
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`judgment.” Allure Energy, Inc. v. Nest Labs, Inc., No. 9-13-CV-102, 2015 WL 11110607, at *2
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`(E.D. Tex. May 11, 2015). Defendants therefore cannot meet their burden to show that the
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`priority applications fail to meet the written description requirement.
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`1.
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`The Priority Applications Disclose a Precise Chemical Formula and
`Narrow the Options from Which the Substituents Could Be Selected
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`Defendants’ motion ignores a crucial aspect of the claims: the recitation of a precise
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`formula depicting the structure of the claimed compound. Claim 1 recites an ADC having a
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`linker unit defined by a formula “-Aa-Ww-Yy-”, which consists of the specific chemical structure
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`for maleimidocaproyl (Aa), a tetrapeptide amino acid unit (Ww) consisting of either glycine or
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`phenylalanine peptides, and a Spacer unit (Yy). (’039 Pat. at Claim 1; Bertozzi ¶¶ 63, 85, 295.)
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`This linker is capable of linking, on the one end, to the antibody (Ab) via a sulfur atom (S) on a
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`cysteine residue of the antibody, and on the other end, to a drug moiety (D). (Id.)
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`The claim further defines each of the amino acids W in the tetrapeptide amino acid unit
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`as having the structure below, wherein R19 is a side chain that can be either a hydrogen (resulting
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`in the amino acid glycine, depicted as gly or G) or benzyl (resulting in the amino acid
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`phenylalanine, depicted as phe or F). (Bertozzi ¶ 295; ’039 Pat. at Claim 1.)
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`Thus, the claims of the ’039 patent provide a specific chemical formula for the linker, including
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`each of the components of this linker, which serves to link an antibody (Ab) to a drug moiety
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`(D). (Id.) And they further define the substituents for the tetrapeptide amino acid unit by a
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`specific formula having a particular structure. (Id.)
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`The priority applications disclose this precise formula, and also define the substituents,
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`including those that form the tetrapeptide amino acid unit. For example, the ’340 application
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`(which was filed on November 5, 2004) provides the same formula recited in Claim 1:
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`(Bertozzi ¶ 62; Compare ’340 application ¶ 0715 to ’039 Pat. at 331:37–45.) The ’340
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`application also provides a structure for each amino acid within the peptide unit, which is exactly
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`the same structure recited in claim 1:
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`(Bertozzi ¶¶ 64, 296; ’340 application ¶ 0684.)
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`The ’340 application discloses detailed information about the amino acid unit. (Bertozzi
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`¶ 64.) In particular, it discloses that the amino acid unit “is a dipeptide, tripeptide, tetrapeptide,
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`pentapeptide . . . or dodecapeptide unit,” and further states that in one embodiment, the amino
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`acid unit “is a dipeptide, tripeptide, tetrapeptide or pentapeptide.” (Bertozzi ¶¶ 64, 296; ’340
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`application ¶¶ 0684, 0694) (emphasis added).) The application states that each R19 side chain is
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`selected from a group of 39 side chains, including hydrogen and benzyl (corresponding to
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`glycine and phenylalanine, respectively), which are the side chains claimed in claim 1 of the
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`’039 patent. (Bertozzi ¶¶ 65, 296; ’340 application ¶ 0685.) Thus the ’340 application includes
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`within its written description a tetrapeptide that consists of amino acids with R19 groups of either
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`hydrogen (gly) or phenylalanine (phe). (Bertozzi ¶ 297.)
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`The ’340 application also provides illustrative examples of tetrapeptides, which were
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`well-known in the art. (See, e.g., Opp. Ex. 10, SGIEDTX00002840 at -899; Opp. Ex. 11,
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`SGIEDTX00362535; Opp. Ex. 12, SGIEDTX00362513; Opp. Ex. 13, SGIEDTX00362444; see
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`also Bertozzi ¶ 298.) The disclosed tetrapeptides are depicted by the following formula:
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`(Bertozzi ¶ 298.) The formula provides a total of four types of amino acids for use in the
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`tetrapetides: glycine (H), phenylalanine (benzyl), leucine (isobutyl), and alanine (methyl). (Id.)
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`The formula then depicts two tetrapeptides, made up of two sets of these four amino acids. The
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`first exemplary tetrapeptide consists of three types of amino acids: glycine, phenylalanine, and
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`leucine. The second exemplary tetrapeptide consists of just two types of amino acids: alanine
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`and leucine. (Id.)
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`Defendants argue that the priority applications’ disclosure results in “nearly 48 million
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`linkers in the tetrapeptide category alone,” a disclosure that they argue is too broad to support the
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`subgenus of gly/phe tetrapeptides. (Mot. at 20.) Yet Defendants admit that the scope of the
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`claims is limited to only “a minute subgenus” of those linkers: only 81 tetrapeptides, not
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`millions. (Mot. at 16; see also Opp. Ex. 14, Lambert Tr. 81:7-15, 94:10-95:14 (admitting that by
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`the 2000s, synthesizing tetrapeptide sequences was “well known and fairly straightforward” and
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`making 81 tetrapeptide sequences “would be doable.”).) Defendants also dismiss th