Case 2:20-cv-00337-JRG Document 123 Filed 07/19/21 Page 1 of 28 PageID #: 5074
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`IN THE UNITED STATES DISTRICT COURT
`EASTERN DISTRICT OF TEXAS
`MARSHALL DIVISION
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`SEAGEN INC.,
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`v.
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`Civil Action No. 2:20-CV-00337-JRG
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`Plaintiff,
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`
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`DAIICHI SANKYO CO., LTD.,
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`Defendant.
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`PLAINTIFF SEAGEN INC.’S
`CLAIM CONSTRUCTION BRIEF
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`sf-4511142
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`Case 2:20-cv-00337-JRG Document 123 Filed 07/19/21 Page 2 of 28 PageID #: 5075
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`TABLE OF CONTENTS
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`Page
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`INTRODUCTION ............................................................................................................. 1
`I.
`OVERVIEW OF THE ’039 PATENT ............................................................................... 1
`II.
`APPLICABLE LEGAL PRINCIPLES .............................................................................. 3
`III.
`IV. ARGUMENT ..................................................................................................................... 5
`A.
`“Y is a Spacer unit”................................................................................................ 5
`1.
`DSC’s proposal contradicts the intrinsic evidence .................................... 6
`2.
`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction .............................................................. 7
`“D is a drug moiety” .............................................................................................. 8
`1.
`DSC’s proposal contradicts the intrinsic evidence .................................... 9
`2.
`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction ............................................................ 11
`“p ranges from 1 to about 20” .............................................................................. 11
`1.
`DSC’s proposal contradicts the intrinsic evidence .................................. 12
`2.
`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction ............................................................ 13
`“wherein the S is a sulfur atom on a cysteine residue of the antibody” ............... 13
`1.
`DSC’s proposal contradicts the intrinsic evidence .................................. 15
`2.
`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction ............................................................ 16
`DSC has failed to meet its high burden of showing indefiniteness ......... 17
`3.
`“wherein the drug moiety is intracellularly cleaved in a patient from the
`antibody of the antibody-drug conjugate or an intracellular metabolite of
`the antibody-drug conjugate” ............................................................................... 18
`“wherein Y is a self-immolative spacer” ............................................................. 21
`1.
`DSC’s proposal contradicts the intrinsic evidence .................................. 21
`2.
`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction ............................................................ 22
`CONCLUSION ................................................................................................................ 23
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`B.
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`C.
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`D.
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`E.
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`F.
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`V.
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`TABLE OF AUTHORITIES
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`Cases Page(s)
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`01 Communique Lab’y, Inc. v. LogMeIn, Inc.,
`687 F.3d 1292 (Fed. Cir. 2012)................................................................................................15
`
`Alloc, Inc. v. Int’l Trade Comm’n,
`342 F.3d 1361 (Fed. Cir. 2003)..................................................................................................3
`
`Azure Networks, LLC v. CSR PLC,
`771 F.3d 1336 (Fed. Cir. 2014), vacated on other grounds...................................................1, 3
`
`BASF Corp. v. Johnson Matthey Inc.,
`875 F.3d 1360 (Fed. Cir. 2017)..................................................................................................4
`
`Golden Bridge Tech., Inc. v. Apple Inc.,
`758 F.3d 1362 (Fed. Cir. 2014)..............................................................................................3, 4
`
`Hill-Rom Servs., Inc. v. Stryker Corp.,
`755 F.3d 1367 (Fed. Cir. 2014)..................................................................................................4
`
`Nautilus, Inc. v. Biosig Instruments, Inc.,
`572 U.S. 898 (2014) .............................................................................................................4, 17
`
`Oatey Co. v. IPS Corp.,
`514 F.3d 1271 (Fed. Cir. 2008)..................................................................................................6
`
`Optis Wireless Tech., LLC v. Apple Inc.,
`No. 2:19-cv-00066-JRG, 2020 WL 1692968 (E.D. Tex. Apr. 7, 2020) ....................................1
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc)..............................................................................3, 4
`
`Renishaw PLC v. Marposs Societa’ per Azioni,
`158 F.3d 1243 (Fed. Cir. 1998)..................................................................................................3
`
`Teva Pharms. USA, Inc. v. Sandoz, Inc.,
`574 U.S. 318 (2015) ...................................................................................................................4
`
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996)....................................................................................................4
`
`Whirlpool Corp. v. Ozcan,
`No. 2:15-cv-2103-JRG, 2016 WL 7474517 (E.D. Tex. Dec. 29, 2016) ..................................18
`
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`Case 2:20-cv-00337-JRG Document 123 Filed 07/19/21 Page 4 of 28 PageID #: 5077
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`I.
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`INTRODUCTION
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`A person of ordinary skill in the art would have no trouble understanding the terms in the
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`asserted claims of U.S. Patent No. 10,808,039 (the ’039 patent) and they require no construction.
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`Given the “heavy presumption” that claim terms carry their plain and ordinary meaning to those
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`skilled in the art, this Court should decline to redefine the claim terms except to the extent
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`necessary to assist the lay jury in understanding the terms. Optis Wireless Tech., LLC v. Apple
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`Inc., No. 2:19-cv-00066-JRG, 2020 WL 1692968, at *1 (E.D. Tex. Apr. 7, 2020) (quoting Azure
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`Networks, LLC v. CSR PLC, 771 F.3d 1336, 1347 (Fed. Cir. 2014), vacated on other grounds).
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`DSC asks the Court to disregard the plain meaning of the claim terms, and proposes
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`constructions that introduce additional limitations into the claims. These proposals conflict with
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`the intrinsic and extrinsic evidence, and hence violate the basic tenets of claim construction. A
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`straightforward application of these tenets favors adoption of Seagen’s proposals, which are
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`consistent with and fully supported by the intrinsic and extrinsic evidence, including the
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`declaration of expert Dr. Pamela A. Trail.
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`II.
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`OVERVIEW OF THE ’039 PATENT
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`The inventions in Seagen’s ’039 patent concern antibody-drug conjugate (“ADC”)
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`technology. (See, e.g., Ex. 11, ’039 patent at 1:58-2:3.) This technology enables the delivery of
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`chemotherapeutic drugs directly to cancer cells by linking them to antibodies. (See id. at
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`1:58-3:14.) The patent claims are directed to ADCs comprising a “protease cleavable linker,”
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`which is a linker that is capable of being cleaved (or cut) by an enzyme called a “protease” to
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`release the drug. (See id. at 66:43-46, 67:56-60, 159:9-13, 160:59-64, 331:35-332:66.)
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`The claims cover ADCs with linkers having a specific formula. Claim 1, with terms at
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`1 All citations to “Ex.” are to the Declaration of Teresa A. MacLean in Support of Plaintiff
`Seagen Inc.’s Claim Construction Brief (“MacLean Decl.”).
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`issue highlighted, recites:
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`(Id. at 331:35-332:40.) In this claim, a maliemidocaproyl or “mc” molecule links to S, a sulfur
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`atom on a cysteine residue of the antibody. (Id. at 331:36-45, 331:49, 332:35-36.) The amino
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`acid unit Ww is a tetrapeptide of four amino acids in length, with each amino acid having the
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`formula shown above in which R19 is either hydrogen or benzyl. (Id. at 331:36-63.) The amino
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`acid glycine (abbreviated “G” or “Gly”) has hydrogen as the R19 group and the amino acid
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`phenylalanine (abbreviated “F” or “Phe”) has benzyl as the R19 group in this formula. (Id.)
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`Thus, the Ww unit in Claim 1 is directed to a tetrapeptide in which each amino acid is either G or
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`F. p is a variable that represents the average number of drugs linked to each antibody, which
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`ranges from 1 to about 20. (Id. at 51:33-41, 331:67.) D is the drug portion attached by the
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`linker. (Id. at 331:66.) Claim 1 provides that the drug is intracellularly cleaved (i.e., separated
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`within a cell) from the antibody portion of the ADC. (Id. at 332:37-40.)
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`Claim 2, which depends from Claim 1, is also at issue. Claim 2 provides that the spacer
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`unit Yy is a “self-immolative” spacer, meaning it degrades following cleavage of the amino acid
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`unit to release the drug.2 (Id. at 332:41-42.)
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`III. APPLICABLE LEGAL PRINCIPLES
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`This Court is very familiar with claim construction principles. “It is a ‘bedrock principle’
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`of patent law that ‘the claims of a patent define the invention to which the patentee is entitled the
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`right to exclude.’” Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en banc)
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`(quoting Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1115 (Fed.
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`Cir. 2004)). The general rule is that each claim term is construed according to its ordinary and
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`accustomed meaning as understood by one of ordinary skill in the art at the time of the invention
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`in the context of the patent. Phillips, 415 F.3d at 1312–13; Alloc, Inc. v. Int’l Trade Comm’n,
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`342 F.3d 1361, 1368 (Fed. Cir. 2003); Azure Networks, 771 F.3d at 1347 (“There is a heavy
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`presumption that claim terms carry their accustomed meaning in the relevant community at the
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`relevant time.”) (quotations omitted). “[T]he claim construction inquiry … begins and ends in
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`all cases with the actual words of the claim.” Renishaw PLC v. Marposs Societa’ per Azioni, 158
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`F.3d 1243, 1248 (Fed. Cir. 1998). A term’s context in the asserted claim can be instructive.
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`Phillips, 415 F.3d at 1314.
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`The plain and ordinary meaning of claim terms must be used unless one of two limited
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`exceptions apply: “1) when a patentee sets out a definition and acts as his own lexicographer, or
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`2) when the patentee disavows the full scope of the claim term either in the specification or
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`during prosecution.” Golden Bridge Tech., Inc. v. Apple Inc., 758 F.3d 1362, 1365 (Fed. Cir.
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`2014) (citations omitted); see Hill-Rom Servs., Inc. v. Stryker Corp., 755 F.3d 1367, 1371 (Fed.
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`2 While the parties’ June 4, 2021 Joint Claim Construction Statement (Dkt. 106) included terms
`for claims 6 through 8, Seagen is no longer asserting these claims in this dispute. Thus, this brief
`will not address terms that are no longer at issue.
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`Cir. 2014) (citation omitted). When construction is necessary, terms should be construed by
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`examining the intrinsic evidence. Phillips, 415 F.3d at 1313-17.
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`While the claims define the invention and are the primary source of intrinsic evidence,
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`they do not stand alone. Id. at 1315. The patent specification “is always highly relevant to the
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`claim construction analysis.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.
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`Cir. 1996). But it is improper to “read limitations from the embodiments in the specification into
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`the claims” even where there is only one embodiment. Hill-Rom, 755 F.3d at 1371 (citing
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`Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 904 (Fed. Cir. 2004)).
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`The Court may also consult extrinsic evidence to understand “the background science or
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`the meaning of a term in the relevant art during the relevant time period.” Teva Pharms. USA,
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`Inc. v. Sandoz, Inc., 574 U.S. 318, 331 (2015). Technical dictionaries and treatises may help the
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`Court understand the underlying technology and the manner in which one skilled in the art might
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`use a claim term. Phillips, 415 F.3d at 1317-18.
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`DSC argues that certain claim terms are indefinite. A patent is definite when its “claims,
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`viewed in light of the specification and prosecution history, inform those skilled in the art about
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`the scope of the invention with reasonable certainty.” Nautilus, Inc. v. Biosig Instruments, Inc.,
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`572 U.S. 898, 910 (2014). “[A]bsolute precision is unattainable.” Id. Whether a claim is
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`indefinite is determined from the perspective of one of ordinary skill in the art as of the time the
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`application for the patent was filed. Id. at 908. As it is a challenge to the validity of a patent, the
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`failure of any claim in suit to comply with § 112 must be shown by clear and convincing
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`evidence. BASF Corp. v. Johnson Matthey Inc., 875 F.3d 1360, 1365 (Fed. Cir. 2017).
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`IV. ARGUMENT
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`A.
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`“Y is a Spacer unit”
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`Term
`(1.5) “Y is a
`Spacer unit”
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`Plaintiff
`Plain meaning/no construction is
`necessary. Alternatively: “Y is a unit
`that links the amino acid unit to a drug.”
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`Defendant
`“one or more atoms that links
`Ww to a nitrogen atom of D,
`the drug moiety”
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`
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`The term “Y is a Spacer unit” refers to the part of an ADC that links an amino acid unit to
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`a drug unit. It does not require construction. “Spacer unit” is a commonly understood term
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`within the field of ADCs. The placement of Y between the Ww (amino acid) and D (drug) units
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`within Claim 1 also makes its context clear. With this context, a person of ordinary skill would
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`understand that Y is a unit that links the drug unit to the amino acid unit, providing space
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`between them. (See Declaration of Pamela A. Trail (“Trail Decl.”) ¶¶ 16-17, 19-20.)
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`DSC’s construction adds limitations that do not appear in the claim and do not comport
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`with the plain meaning of the term. DSC narrows the genus of covered spacer units to include
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`only those that link to “a nitrogen atom of D, the drug moiety.” A person of ordinary skill would
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`not have understood the term “spacer unit” to be so limited. Linkages to drugs through atoms
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`other than nitrogen exist and were known at the time of the invention. (See id. ¶ 21.)
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`1.
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`DSC’s proposal contradicts the intrinsic evidence
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`The intrinsic evidence does not support the narrowing construction that DSC proposes.
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`Rather, in the section titled “Spacer Unit,” the specification expressly states that the spacer unit
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`Y “links an Amino Acid unit to the Drug moiety when an Amino Acid unit is present.” (Ex. 1,
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`’039 patent at 68:14-16.) This matches the plain meaning and Seagen’s alternative proposal
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`almost verbatim.
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`Nowhere in the specification is there a requirement that the spacer unit must connect to a
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`nitrogen atom on the drug. In fact, the specification provides multiple counter-examples where
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`the spacer unit is connected to groups on a drug that do not contain nitrogen. These include
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`embodiments where the spacer unit is connected to a drug via a “carbonate, carbamate or ether
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`group.” (See id. at 68:51-57 (emphasis added to identify groups that do not contain a nitrogen
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`atom).) Figures 21 and 22 further exemplify these linkages. (Id. at 21:5-10, Figs. 21-22.) In the
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`context of Figure 21, the specification cites Seagen inventor Dr. Brian Toki’s work, where he
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`explains that the spacer can be attached to a drug via linkage to an oxygen rather than a nitrogen-
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`containing group. (Id. at 68:54-57 (citing Ex. 2 (SGIEDTX00040149 at 40150-40153).) DSC’s
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`construction would improperly exclude these embodiments. Courts “normally do not interpret
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`claim terms in a way that excludes embodiments disclosed in the specification.” Oatey Co. v.
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`IPS Corp., 514 F.3d 1271, 1276-77 (Fed. Cir. 2008) (reversing a claim construction that
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`excluded an embodiment).
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`DSC can point to no clear and unmistakable disavowals in the specification or the
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`prosecution history that would support inserting a limitation not found in the claim language.
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`Nor can it show lexicography that restricts the meaning of the term. While the specification
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`describes linkages to a nitrogen-containing “amine” group in a drug, this is only an “exemplary
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`embodiment” of the invention. (Ex. 1, ’039 patent at 146:44-46.) It would be improper to limit
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`the definition of spacer to this exemplary embodiment.3
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`2.
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`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction
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`The concept of a “spacer unit” is well-understood in the field of ADCs. (See Trail
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`Decl. ¶¶ 16, 19-20.) Bristol Myers Squibb (“BMS”) used this term in the 1990s in connection
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`with its ADC development to refer to a unit that separates the drug from other parts of the ADC.
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`(Id. ¶ 19.) In 1981, Carl et al. reported a chemical connector group that solved instability
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`problems by “spacing” the drug away from other parts of a conjugate. (Id. ¶ 20 (citing Ex. 3
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`(SGIEDTX00042264 at 42264)).) Ajaj et al. described a spacer as a unit placed between an
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`amino acid unit and the drug to ensure access to the site of cleavage. (Id. (citing Ex. 4
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`(SGIEDTX00042200 at 42201)).) Many other publications describe a spacer unit in the same
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`way. (See, e.g., Exs. 5-8 (SGIEDTX00042166 at 42177, SGIEDTX00042254 at 42254-42255,
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`and SGIEDTX00042284 at 42285, SGIEDTX00039597 at 39597-39598).) None of these
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`publications limited the concept of ADC spacer units only to units that bond to a nitrogen atom
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`in the drug.
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`3 DSC also proposes that the term be construed to include the limitation “one or more atoms” in
`place of the commonly understood term “unit.” The specification of the patent does not define
`the term “unit” as being “one or more atoms,” so there is no reason to deviate from the plain and
`ordinary meaning. Nor is there any dispute that DSC’s construction of “unit” would resolve.
`Hence, the inclusion of this unnecessary verbiage should be rejected.
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`B.
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`“D is a drug moiety”
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`Terms
`(1.7) “D is a
`drug moiety”
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`Plaintiff
`Plain meaning/no
`construction is
`necessary.
`Alternatively: “D is a
`drug portion.”
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`Defendant
`“a drug of the dolastatin/auristatin-type having a
`nitrogen atom that can form a bond with the
`Spacer unit when y=1 or 2, or with the C-terminal
`carboxyl group of an Amino Acid unit when y=0”
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`The term “D is a drug moiety” is a simple term that would be readily understood by a
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`person of ordinary skill and requires no construction. (See, e.g., Trail Decl. ¶¶ 22-23.) To the
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`extent helpful to lay jurors, the scientific term “moiety” could be construed as “portion,” as D
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`refers to the “drug portion” (or unit) of the ADC. (Id. ¶ 23.)
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`DSC’s proposal takes a simple term and grafts additional limitations to it. First, DSC’s
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`construction would limit the “drug moiety” to drugs “of the dolastatin/auristatin-type.” Second,
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`DSC’s construction would, again, limit drug-linkages to those involving “a nitrogen atom.” A
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`person of ordinary skill would not have understood “drug moiety” to be limited to any particular
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`drug type, as many different drugs could be and were used in ADCs, including by the inventors.
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`(Id. ¶¶ 24-27.) As discussed above, moreover, the inventors described other drug-linkages than
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`those to a nitrogen-containing group. Hence, neither of DSC’s proposed additional limitations
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`comport with the plain meaning of the term.
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`1.
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`DSC’s proposal contradicts the intrinsic evidence
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`The limitations that DSC proposes to add through its construction find no support in the
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`claims. Claim 1 depicts the drug moiety, D, as the drug portion of the claimed ADC. (Ex. 1,
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`’039 patent at 331:36-45, 331:66.) None of the claims limit D to drugs of the
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`“dolastatin/auristatin-type” or drugs having a nitrogen atom that can form a bond with the linker.
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`The specification also is not so limited. Rather, it describes the field of invention broadly
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`as including “Drug-Linker-Ligand Conjugates” without limitation to particular drug types. (Id.
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`at 1:55-63.) In the background, it provides that the “use of antibody-drug conjugates for the
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`local delivery of cytotoxic or cytostatic agents” was known, and explicitly states that the
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`chemotherapeutic drugs that have been used in these methods include: “daunomycin,
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`doxorubicin, methotrexate, and vindesine,” as well as “maytansinoids” and “calicheamicin.” (Id.
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`at 2:43-3:7.) The specification also describes multiple different mechanisms of action for these
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`drugs, including “tubulin binding,” “DNA binding,” and “topoisomerase inhibition.” (Id. at
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`3:7-12.)4 In support, the specification cites a book chapter by Dr. Peter Senter on ADCs where
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`the attached drugs were doxorubicin (a topoisomerase inhibitor), calicheamicin (a DNA binder),
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`and maytansinoids, taxanes, and auristatins (tubulin binders). (Id. (citing Ex. 9
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`(SGIEDTX00041108 at 41109-41113)).) The specification also cites work by inventor Dr. Toki
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`on ADCs with the drug etoposide (a topoisomerase inhibitor). (Ex. 1, ’039 patent at 68:54-57
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`(citing Ex. 2 (SGIEDTX00040149 at 40150-40153)).)
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`Elsewhere, in the section describing some of the patent’s key terms, the specification
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`4 Drugs of the dolastatin/auristatin-type fall in only one of these categories: “tubulin binding”
`agents. (See Ex. 5 (SGIEDTX00042166 at 42180); Ex. 9 (SGIEDTX00041108 at 41113).)
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`states that ADCs are a kind of “prodrug” that are “capable of being enzymatically or
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`hydrolytically activated.” (Ex. 1, ’039 patent at 34:50-55.) The specification then provides that
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`“cytotoxic drugs that can be derivatized into a prodrug form for use in this invention include” a
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`long list of “chemotherapeutic agents.” (Id. at 35:2-5.) This list incorporates all of the agents
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`discussed above, those of the dolastatin/auristatin-type, and many others. (Id. at 31:39-33:31.)
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`These sections of the specification make clear the inventors contemplated that the claimed ADCs
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`may use many different chemotherapeutic drugs—not solely those of the dolastatin/auristatin-
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`type. It would be inconsistent with this intrinsic evidence to limit D to only this single class of
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`chemotherapeutic drugs.
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`While the specification does describe embodiments in which D is a drug of the
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`dolastatin/auristatin-type, including examples where they are linked via a nitrogen atom, these
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`are only an “aspect” of the invention that the specification explains is “illustrative” and
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`“exemplary.” (See, e.g., id. at 44:56-45:7, 74:11-77:15, 146:44-47.) No language restricts the
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`claimed invention to these examples, and other aspects of the invention are not so limited. (See,
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`e.g., id. at 19:4-11 (referring to compositions including drugs with mechanisms of action that
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`differ from tubulin binding, as occurs with the dolastatin/auristatin-type).)
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`Nor can DSC point to a clear and unmistakable disavowal in the specification or the
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`prosecution history that would support limiting the claims only to dolastatin/auristatin-type
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`embodiments of D. In prosecution, the examiner specifically determined that D encompasses
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`non-dolastatin/auristatin-type drugs, including doxorubicin, and Seagen did not disclaim that
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`interpretation. (See Ex. 10, 11-06-2019 Non-Final Rejection at 4 (finding D could be “the drug
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`moiety doxorubicin”) (SGIEDTX00000001 at 00147).)
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`2.
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`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction
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`A “drug moiety” is a well-understood concept in the field of ADCs that is not limited to
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`drugs of the dolastatin/auristatin-type. Within the chemical and biological sciences, “moiety”
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`means: “[a] part or portion of a molecule, generally complex, having a characteristic chemical or
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`pharmacological property.” (See Trail Decl. ¶ 24 (citing Ex. 11 (SGIEDTX00042231 at
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`42237)).) Literature from the 1990s and early 2000s describes many different drug moieties that
`
`could be and were used in ADCs, including a variety of cytotoxic drugs such as calicheamicins,
`
`maytansinoids, auristatins, and duocarmycins. (Trail Decl. ¶¶ 25-26 (citing Ex. 12
`
`(SGIEDTX00042266 at 42266); Ex. 13 (SGIEDTX00042326 at 42331, 42330-42336); Ex. 14
`
`(SGIEDTX00042110 at 42140-42143)).) This broad interpretation is also supported in
`
`contemporaneous articles by Seagen inventor Dr. Senter, whose work has involved many
`
`different types of drugs for use in ADCs. (Trail Decl. ¶ 26 (citing Ex. 15 (SGIEDTX00041635
`
`at 41641)).)
`
`C.
`
`“p ranges from 1 to about 20”
`
`Terms
`(1.8) “p
`ranges from 1
`to about 20”
`
`Plaintiff
`Plain meaning/no construction is necessary. A person of
`ordinary skill in the art would understand with reasonable
`certainty the scope of what is claimed. Alternatively: “The
`drug to antibody ratio ranges from 1 to about 20.” The drug
`to antibody ratio, p, does not need to be an integer.
`
`Defendant
`“p” must be
`an integer.
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`
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`
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`The term “p ranges from 1 to about 20” does not require construction and should be given
`
`its plain and ordinary meaning. “p” is the “drug to antibody ratio” or “DAR” of an ADC. This
`
`commonly understood concept within the field of ADCs refers to the average number of drug
`
`molecules per antibody, and since it is an average, the ratio will often be a non-integer value.
`
`(See Trail Decl. ¶¶ 28-34.) DSC’s proposal to restrict p to integer values conflicts with the plain
`
`meaning of the term as well as the intrinsic and extrinsic evidence.
`
`1.
`
`DSC’s proposal contradicts the intrinsic evidence
`
`DSC’s proposed construction of “p” is inconsistent with the use of the term in the claims.
`
`Claim 1 states that “p ranges from 1 to about 20,” suggesting that p can be a non-integer value
`
`short of 20. (Ex. 1, ’039 patent at 331:67 (emphasis added).) Claims 4 and 5 similarly provide
`
`that “p is about 3 to about 8” and “p is about 8” respectively. (Id. at 332:44-48.) If DSC’s
`
`construction were correct, there would be no need to use the term “about” in the claims.
`
`The specification also expressly contradicts DSC’s proposed construction. It states that
`
`the “drug loading is represented by p, the average number of drug molecules per antibody in a
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`molecule” and describes methods to characterize p. (Ex. 1, ’039 patent at 51:33-47 (emphasis
`
`added).) Nowhere does the specification state that this average must be an integer value, as DSC
`
`proposes. Nor would an average necessarily result in an integer absent rounding, which the
`
`specification does not propose. Rather, the specification describes many ADC preparations
`
`having non-integer p values, including Figure 7 (3.8, 4.1, and 4.8 drug/Ab), Figure 8 (same),
`
`Figure 9 (3.8, 3.9, and 4.1 drug/Ab), and Figure 10 (4.1, 3.3, and 3.7 drug/Ab). (See, e.g., id. at
`
`Figs. 7-10, 19:63-20:19.) DSC’s construction would improperly exclude these embodiments.
`
`2.
`
`The extrinsic evidence confirms the plain meaning and Seagen’s
`alternative proposed construction
`
`In the ADC field, the concept to which “p” is directed—the drug to antibody ratio—is
`
`well-understood and is not considered to be limited to integer values. (Trail Decl. ¶¶ 30-34.)
`
`For example, Walker et al. (2002) reported the synthesis of camptothecin immunoconjugates
`
`with drug to antibody ratios of 7.51 and 5.26. (Ex. 7 (SGIEDTX00042284 at 42285-86).)
`
`Hamblett et al. (2004) reported methods to create partially loaded ADC populations with drug to
`
`antibody ratios of “4.0 to 4.2.” (Ex. 16 (SGIEDTX00042158 at 42161).) Even DSC’s
`
`publications describe non-integer drug to antibody ratios. (Exs. 17-18 (SGIEDTX00008257 at
`
`8258, 8260; SGIEDTX00008240 at 8242).)
`
`D.
`
`“wherein the S is a sulfur atom on a cysteine residue of the antibody”
`
`Terms
`(1.9)
`“wherein the
`S is a sulfur
`atom on a
`cysteine
`residue of the
`antibody”
`
`Plaintiff
`Plain meaning/no
`construction is
`necessary. A person of
`ordinary skill in the art
`would understand with
`reasonable certainty the
`scope of what is claimed.
`Alternatively: “wherein
`S is a sulfur atom on a
`cysteine amino acid in
`the antibody.”
`
`Defendant
`Indefinite (the claim does not provide reasonable
`certainty at least regarding how the POSA would
`understand the scope of “a sulfur atom on a
`cysteine residue of the antibody” given that “p
`ranges from 1 to about 20”)
`
`Alternatively, each of the p
`
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`Terms
`
`
`
`
`Plaintiff
`
`Defendant
`
`are attached to a single sulfur atom.
`
`
`
`
`This term “S is a sulfur atom on a cysteine residue of the antibody” would be
`
`straightforward to a person of ordinary skill and does not require construction. This term refers
`
`to the way each drug-linker unit (the part shown in parentheses in the formula of Claim 1) is
`
`attached to the antibody. Skilled artisans would understand that this formula and the
`
`accompanying text describe attachment of each drug-linker unit to its own “cysteine residue” in
`
`the antibody, and that each individual cysteine residue would have a “sulfur atom” (denoted as
`
`an “S”) available for creating the bond between the antibody and drug-linker unit. (See Trail
`
`Decl. ¶¶ 35-36, 38-40.) The words “sulfur” and “cysteine residue” are commonly used within
`
`the chemical and biologic sciences. And it is black letter law that the reference to “a sulfur
`
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`atom” in Claim 1 would include “one or more” sulfur atoms. 01 Communique Lab’y, Inc. v.
`
`LogMeIn, Inc., 687 F.3d 1292, 1297 (Fed. Cir. 2012) (“As a general rule, the words ‘a’ or ‘an’ in
`
`a patent claim carry the meaning of ‘one or more’. . . The exceptions to this rule are extremely
`
`limited: a patentee must evince a clear intent to limit ‘a’ or ‘an’ to ‘one.’”) (quotations omitted).
`
`Thus, if p is “about 8” as in Claim 5, there would need to be eight cysteine residues in the
`
`antibody with sulfur atoms available for bonding. Most antibodies have eight naturally occurring
`
`cysteines, and they can be engineered to include additional accessible cysteines. (See Trail Decl.
`
`¶¶ 39, 62.)
`
`In contrast, DSC would have the Court insert limitations into the term so that every drug-
`
`linker unit, “p,” must bond with a “single sulfur atom.” This construction would mean that, in
`
`Claim 5, all “about 8” drug-linker units would have to be bonded to the same sulfur atom. As
`
`sulfur can only support six bonds maximum (as opposed to “about 8”), the construction would
`
`result in a scientific impossibility that DSC asserts renders the claim indefinite. Yet DSC
`
`presents no evidence that this is how one of ordinary skill would interpret the claims, and the
`
`inoperabil