UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________
`
`DAIICHI SANKYO, INC. and
`ASTRAZENECA PHARMACEUTICALS, LP
`Petitioner,
`
`v.
`
`SEAGEN INC.
`Patent Owner.
`
`Case No. PGR2021-00030
`Patent 10,808,039
`
`_______________
`
`____________________________________________________________
`
`PATENT OWNER RESPONSE
`
`

`

`PGR2021-00030
`
`
`TABLE OF CONTENTS
`
`
`
`
`
`Page
`TABLE OF AUTHORITIES ................................................................................... iv
`PATENT OWNERS EXHIBIT LIST ....................................................................... x
`I. 
`INTRODUCTION .......................................................................................... 1 
`II. 
`BACKGROUND ............................................................................................ 4 
`A. 
`The Person of Ordinary Skill in the Art ............................................... 4 
`B. 
`Claim Construction .............................................................................. 4 
`C. 
`Scientific Background .......................................................................... 5 
`1. 
`Pre-ADC Cancer Therapies and Their Drawbacks .................... 5 
`2. 
`ADC Linker Structures, Payloads, and Attachment
`Chemistries ................................................................................. 7 
`Seagen’s ADC Technology ...................................................... 12 
`3. 
`Determining Intracellular Cleavage of Drugs from ADCs ...... 14 
`4. 
`The ’039 Patent .................................................................................. 15 
`1. 
`The Applications Preceding the ’039 Patent............................ 15 
`2. 
`The ’039 Patent Specification .................................................. 17 
`3. 
`The Claims at Issue .................................................................. 22 
`III.  ARGUMENT ................................................................................................ 23 
`Petitioner Has Not Shown that the’039 Specification Fails to
`A. 
`Enable the Challenged Claims ........................................................... 24 
`The ’039 Patent Enables a Variety of Drugs and
`1. 
`Attachment Chemistries for Use in the Claimed ADCs .......... 25 
`The Art as of 2004 Taught How to Join a Variety
`a. 
`of Drugs Using a Variety of Attachment
`Chemistries for Making ADCs ...................................... 25 
`Petitioner’s Arguments About “Retaining
`Activity” and Other Unclaimed Features Have No
`Bearing on the Claimed ADCs ...................................... 33 
`Petitioner’s Enablement Analysis Improperly
`Relies on Post-Priority Date Evidence .......................... 37 
`
`D. 
`
`b. 
`
`c. 
`
` SF-4844289
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`i
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`

`

`PGR2021-00030
`
`
`TABLE OF CONTENTS (cont’d)
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`
`
`Page
`
`2. 
`
`2. 
`
`3. 
`
`B. 
`
` SF-4844289
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`b. 
`
`c. 
`
`b. 
`
`c. 
`
`b. 
`
`c. 
`
`Petitioner Has Not Shown that the Intracellular Cleavage
`Limitation Would Require Undue Experimentation ................ 41 
`Numerous art-recognized assays were available in
`a. 
`2004 to assess intracellular cleavage ............................. 41 
`Petitioner Relies on an Impossible Standard for
`Determining Intracellular Cleavage .............................. 45 
`Petitioner’s Own Product Shows that Intracellular
`Cleavage Can be Readily Determined ........................... 47 
`Petitioner Has Not Shown that the Specification Lacks Written
`Description Support for the ’039 Patent Claims ................................ 49 
`Petitioner Has Not Met Its Burden to Show that the ’039
`1. 
`Patent Lacks Support for the Claimed Drug Unit .................... 50 
`The’039 Patent Is Not Limited to ADCs Using
`a. 
`Dolastatin/Auristatin Derivatives .................................. 50 
`The’039 Patent Discloses Chemistries for
`Attaching Different Classes of Drugs That Fall
`Within the Claimed Genus ............................................ 54 
`Petitioner Has Not Shown that the ’039 Patent
`Lacks Written Description Because of “Common
`Structural Features” ....................................................... 57 
`Petitioner Has Not Met Its Burden to Show that the ’039
`Patent Lacks Support for the Claimed Tetrapeptide
`Amino Acid Unit ...................................................................... 60 
`The ’039 Patent Discloses the Precise Chemical
`a. 
`Formula Claimed ........................................................... 60 
`The ’039 Patent Guides a Person of Ordinary Skill
`Toward the Claimed Tetrapeptides ............................... 69 
`The Nature of the Invention Supports Describing
`Each Unit of the Claimed ADC Formula
`Separately ...................................................................... 73 
`Petitioner’s Written Description Arguments Improperly
`Rely on Post-Priority Date Evidence ....................................... 74 
`ii
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`

`

`PGR2021-00030
`
`
`TABLE OF CONTENTS (cont’d)
`
`
`
`
`
`Page
`
`4. 
`
`C. 
`
`D. 
`
`Petitioner’s Commentary on Seagen’s Prosecution
`Strategy Is Wholly Irrelevant to Written Description .............. 76 
`Petitioner Has Not Shown that the ’039 Patent Claims Are
`Unpatentable for Failing to Set Forth the Subject Matter that the
`Inventors Regarded as Their Invention .............................................. 78 
`Petitioner Has Not Met Its Burden To Show That The
`Challenged Claims Are Anticipated ................................................... 79 
`The ’039 Patent Is Not Eligible for PGR ........................................... 80 
`E. 
`IV.  CONCLUSION ............................................................................................. 82 
`
`
` SF-4844289
`
`iii
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`

`

`PGR2021-00030
`
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`
`
`
`Cases
`Alcon Rsch. Ltd. v. Barr Labs., Inc.,
`745 F.3d 1180 (Fed. Cir. 2014) .......................................................................... 37
`Allen Eng’g Corp. v. Bartell Indus., Inc.,
`299 F.3d 1336 (Fed. Cir. 2002) .......................................................................... 78
`ALZA Corp. v. Andrx Pharms., LLC,
`603 F.3d 935 (Fed. Cir. 2010) ............................................................................ 40
`Amgen Inc. v. Sanofi,
`872 F.3d 1367 (Fed. Cir. 2017) .......................................................................... 75
`Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) (en banc) .................................................... 57, 74
`Atlas Powder Co. v. E.I. du Pont De Nemours & Co.,
`750 F.2d 1569 (Fed. Cir. 1984) .......................................................................... 37
`Blue Calypso, LLC v. Groupon, Inc.,
`815 F.3d 1331 (Fed. Cir. 2016) .......................................................................... 73
`Capon v. Eshhar,
`418 F.3d 1349 (Fed. Cir. 2005) .......................................................................... 57
`Chiron Corp. v. Genentech, Inc.,
`363 F.3d 1247 (Fed. Cir. 2004) .......................................................................... 38
`Concert Pharms., Inc. v. Incyte Corp.,
`No. PGR2017-00034 (P.T.A.B. Jan. 11, 2018) ................................ 34, 35, 37, 48
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`800 F.3d 1375 (Fed. Cir. 2015) .................................................................... 25, 79
`Edwards Lifesciences AG v. CoreValve, Inc.,
`699 F.3d 1305 (Fed. Cir. 2013) .......................................................................... 35
`Fujikawa v. Wattanasin,
`93 F.3d 1559 (Fed. Cir. 1996) ...................................................................... 67, 68
`
` SF-4844289
`
`iv
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`

`

`PGR2021-00030
`
`
`
`
`TABLE OF AUTHORITIES (cont’d)
`
`
`
`Page(s)
`
`Genentech, Inc. v. Novo Nordisk, A/S,
`108 F.3d 1361 (Fed. Cir. 1997) .................................................................... 32, 40
`Heidelberger Druckmaschinen AG v. Hantscho Com. Prods., Inc.,
`21 F.3d 1068 (Fed. Cir. 1994) ............................................................................ 77
`Hybritech, Inc. v. Monoclonal Antibodies, Inc.,
`802 F.2d 1367 (Fed. Cir. 1986) .......................................................................... 24
`Idenix Pharms. LLC v. Gilead Scis. Inc.,
`941 F.3d 1149 (Fed. Cir. 2019) ........................................................ 40, 44, 68, 69
`Immunex Corp. v. Sandoz Inc.,
`964 F.3d 1049 (Fed. Cir. 2020) .............................................................. 51, 52, 55
`In re Alonso,
`545 F.3d 1015 (Fed. Cir. 2008) .......................................................................... 59
`In re Alton,
`76 F.3d 1168 (Fed. Cir. 1996) ............................................................................ 73
`In re Brana,
`51 F.3d 1560 (Fed. Cir. 1995) ............................................................................ 35
`In re Driscoll,
`562 F.2d 1245 (C.C.P.A. 1977) ........................................................ 65, 66, 67, 73
`In re Ruschig,
`379 F.2d 990 (C.C.P.A. 1967) ...................................................................... 66, 67
`In re Wands,
`858 F.2d 731 (Fed. Cir. 1988) ...................................................................... 25, 31
`
`Janssen Pharmaceutica N.V. v. Teva Pharms. USA, Inc. (In re ’318
`Patent Infringement Litig.),
`583 F.3d 1317 (Fed. Cir. 2009) .......................................................................... 37
`Johns Hopkins Univ. v. CellPro, Inc.,
`152 F.3d 1342 (Fed. Cir. 1998) .......................................................................... 24
`
` SF-4844289
`
`v
`
`

`

`PGR2021-00030
`
`
`
`
`TABLE OF AUTHORITIES (cont’d)
`
`
`
`Page(s)
`
`Kingsdown Med. Consultants, Ltd. v. Hollister Inc.,
`863 F.2d 867 (Fed. Cir. 1988) ............................................................................ 77
`Laitram Corp. v. NEC Corp.,
`163 F.3d 1342 (Fed. Cir. 1998) .......................................................................... 55
`Liebel-Flarsheim Co. v. Medrad, Inc.,
`358 F.3d 898 (Fed. Cir. 2004) ............................................................................ 77
`Max Sound Corp. v. Google, Inc.,
`No. 5:14-cv-04412-EJD, 2015 WL 2251060
`(N.D. Cal. May 13, 2015) ................................................................................... 78
`Merck Sharp & Dohme Corp. v. Wyeth LLC,
`No. PGR2017-00016 and No. PGR2017-00017, Paper 9 at 14-15
`(P.T.A.B. Oct. 20, 2017) ..................................................................................... 80
`Mylan Pharms. Inc. v. Yeda Rsch. & Dev. Co.,
`No. PGR2016-00010, Paper 9 (P.T.A.B. Aug. 15, 2016) .................................. 80
`Nautilus, Inc. v. Biosig Instruments, Inc.,
`572 U.S. 898 (2014) ............................................................................................ 78
`Novartis Pharms. Corp. v. Plexxikon Inc.,
`No. PGR2018-00069, Paper 16 (P.T.A.B. Jan. 16, 2019) ...................... 65, 66, 67
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) ........................................................................... 4
`Ricoh Co. v. Nashua Corp.,
`185 F.3d 884 (Fed. Cir. 1999) ............................................................................ 77
`Solomon v. Kimberly-Clark Corp.,
`216 F.3d 1372 (Fed. Cir. 2000) .......................................................................... 78
`Streck, Inc. v. Rsch. & Diagnostic Sys., Inc.,
`665 F.3d 1269 (Fed. Cir. 2012) .......................................................................... 24
`Symantec Corp. v. Finjan, Inc.,
`No. IPR2015-01895, Paper 7 (P.T.A.B. Feb. 26, 2016) ..................................... 17
`vi
`
` SF-4844289
`
`

`

`PGR2021-00030
`
`
`
`
`TABLE OF AUTHORITIES (cont’d)
`
`
`
`Page(s)
`
`Tex. Instruments Inc. v. U.S. Int’l Trade Comm’n,
`871 F.2d 1054 (Fed. Cir. 1989) .......................................................................... 77
`Thorner v. Sony Comput. Ent. Am. LLC,
`669 F.3d 1362 (Fed. Cir. 2012) ............................................................................ 4
`TI Grp. Auto. Sys. (N. Am.), Inc. v. VDO N. Am., L.L.C.,
`375 F.3d 1126 (Fed. Cir. 2004) .......................................................................... 77
`Vas-Cath Inc. v. Mahurkar,
`935 F.2d 1555 (Fed. Cir. 1991) .......................................................................... 74
`Wyeth & Cordis Corp. v. Abbott Lab’ys,
`720 F.3d 1380 (Fed. Cir. 2013) .......................................................................... 40
`Statutes
`35 U.S.C. § 112 .................................................................................................. 24, 60
`35 U.S.C. § 112(b) ............................................................................................... 3, 78
`Other Authorities
`37 C.F.R. § 42.200(b) ................................................................................................ 4
`157 CONG. REC. S1179 (daily ed. Mar. 3, 2011) ..................................................... 81
`157 CONG. REC. S1373 (daily ed. Mar. 8, 2011) ..................................................... 81
`
`
` SF-4844289
`
`vii
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2001
`
`Ex. 2002
`
`Ex. 2003
`
`Ex. 2004
`
`Ex. 2005
`
`Ex. 2006
`
`Ex. 2007
`
`Ex. 2008
`
`PATENT OWNER’S EXHIBIT LIST
`
`
`Description
`Seagen Inc. v. Daiichi Sankyo Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. Feb. 8, 2021), Dkt. 48
`
`Seagen Inc.’s Disclosure of Asserted Claims and
`Infringement Contentions, Seagen Inc. v. Daiichi Sankyo
`Co., Ltd., No. 2:20-cv-00337-JRG (E.D. Tex.), dated Jan. 6,
`2021
`
`Defendant’s Invalidity Contentions, Seagen Inc. v. Daiichi
`Sankyo Co., Ltd., No. 2:20-cv-00337-JRG (E.D. Tex.), dated
`Mar. 3, 2021
`
`Daiichi Sankyo, Inc. v. Seagen Inc., No. 1:20-cv-01524-LPS
`(D. Del. Dec. 18, 2020), Dkt. 11
`
`Daiichi Sankyo, Inc. v. Seagen Inc., No. 1:20-cv-01524-LPS
`(D. Del. Jan. 18, 2021), Dkt. 19
`
`Daiichi Sankyo, Inc. v. Seagen Inc., No. 1:20-cv-01524-LPS
`(D. Del. Jan. 26, 2021), Dkt. 20 (public version)
`
`Argument by Telephone Conference, Daiichi Sankyo, Inc. v.
`Seagen Inc., No. 1:20-cv-01524-LPS (D. Del. Apr. 23, 2021)
`
`Daiichi Sankyo Co., Ltd. v. Seattle Genetics, Inc., No. 1:19-
`cv-02087-CFC (D. Del. Nov. 22, 2019), Dkt. 13
`
`Ex. 2009
`
`Daiichi Sankyo Co., Ltd. v. Seattle Genetics, Inc., No. 1:19-
`cv-02087-LPS (D. Del. Mar. 25, 2020), Dkt. 31
`
`Ex. 2010
`
`Daiichi Sankyo Co., Ltd. v. Seattle Genetics, Inc., No. 1:19-
`cv-02087-LPS (D. Del. Nov. 13, 2020), Dkt. 44
`
` SF-4844289
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`viii
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2011
`
`Ex. 2012
`
`Ex. 2013
`
`Ex. 2014
`
`Ex. 2015
`
`Ex. 2016
`
`Description
`Gene M. Dubowchik and Michael A. Walker, Receptor-
`mediated and enzyme-dependent targeting of cytotoxic
`anticancer drugs, 83 Pharm. & Therapeutics 67-123 (1999)
`
`Franciscus M.H. de Groot et al., Anticancer Prodrugs for
`Application in Monotherapy: Targeting Hypoxia, Tumor-
`Associated Enzymes, and Receptors, 8 Current Med. Chem.
`1093-1122 (2001)
`
`Nitin K. Damle, Tumour-targeted chemotherapy with
`immunoconjugates of calicheamicin, Expert Op. 1445-1452
`(2004)
`
`Franciscus M.H. de Groot et al., Synthesis and Biological
`Evaluation of Novel Prodrugs of Anthracyclines for
`Selective Activation by the Tumor-Associated Protease
`Plasmin, 42(25) J. Med. Chem. 5277-5283 (Dec. 16, 1999)
`
`Damon L. Meyer and Peter D. Senter, Chapter 23. Recent
`Advances in Antibody Drug Conjugates for Cancer Therapy,
`38 Annual Rep. in Med. Chem. 229-237 (2003) (“Meyer &
`Senter 2003”)
`
`Raya Mandler et al., Synthesis and Evaluation of
`Antiproliferative Activity of a Geldanamycin-Herceptin™
`Immunoconjugate, 10 Bioorganic & Med. Chem. Ltrs. 1025-
`1028 (2000)
`
`Ex. 2017
`
`Anna M. Wu and Peter D. Senter, Arming antibodies:
`prospects and challenges for immunoconjugates, 23(9)
`Nature Biotech. 1137-1146 (Sept. 2005)
`
`Ex. 2018
`
`Brian E. Toki et al., Protease-Mediated Fragmentation of p-
`Amidobenzyl Ethers: A New Strategy for the Activation of
`Anticancer Prodrugs, 67 J. Org. Chem. 1866-1872 (2002)
`
` SF-4844289
`
`ix
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2019
`
`Description
`Yelena V. Kovtun and Victor S. Goldmacher, Cell killing by
`antibody–drug conjugates, 255 Cancer Ltrs 232-240 (2007)
`
`Ex. 2020 Michael A. Walker et al., Synthesis of an Immunoconjugate
`of Camptothecin, 12 Bioorganic & Med. Chem. Ltrs. 217-
`219 (2002)
`
`Ex. 2021
`
`Ex. 2022
`
`Ex. 2023
`
`Ex. 2024
`
`Ex. 2025
`
`Requests for Correction of Inventorship in Provisional Patent
`Application for Application Nos. 60/557,116 and
`60/598,899, filed on Nov. 29, 2004
`
`Public Pair Application Data Tab for Provisional Application
`Nos. 60/598,899 and 60/557,116, retrieved from
`https://portal.uspto.gov/pair/PublicPair, on Mar. 8, 2021
`
`Seagen Inc. v. Daiichi Sankyo Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. Jan. 7, 2021), Dkt. 33 (public version)
`
`Lex Machina, Motion Metrics Report for District Judge
`James Rodney Gilstrap (JRG)
`
`Daiichi Sankyo, Inc. v. Seagen Inc., No. 1:20-cv-01524-
`UNA (D. Del. Nov. 13, 2020), Dkt. 4
`
`Ex. 2026
`
`U.S. Patent No. 9,808,537 (Masuda et al.)
`
`Ex. 2027
`
`Ex. 2028
`
`Gene M. Dubowchik and Raymond A. Firestone, Cathepsin
`B-Sensitive Dipeptide Prodrugs. 1. A Model Study of
`Structural Requirements for Efficient Release of
`Doxorubicin, 8 Bioorganic & Med. Chem. Ltrs. 3341-3346
`(1998)
`
`Gene M. Dubowchik et al., Cathepsin B-Sensitive Dipeptide
`Prodrugs. 2. Models of Anticancer Drugs Paclitaxel
`(Taxol®), Mitomycin C and Doxorubicin, 8 Bioorganic &
`Med. Chem. Ltrs. 3347-3352 (1998)
`
` SF-4844289
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`x
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`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2029
`
`Ex. 2030
`
`Description
`Svetlana O Doronina et al., Development of potent
`monoclonal antibody auristatin conjugates for cancer
`therapy, 21(7) Nature Biotech. 778-784, 941 (2003)
`
`Franciscus M.H. de Groot et al., Synthesis and Biological
`Evaluation of 2’-Carbamate-Linked and 2’-Carbonate-
`Linked Prodrugs of Paclitaxel: Selective Activation by the
`Tumor-Associated Protease Plasmin, 43(16) J. Med. Chem.
`3093-3102 (Aug. 10, 2000)
`
`Ex. 2031
`
`Ravi V. J. Chari et al., Immunoconjugates Containing Novel
`Maytansinoids: Promising Anticancer Drugs, 52 Cancer Res.
`127-131 (Jan. 1, 1992)
`
`Ex. 2032
`
`H. Dalton King et al., Monoclonal Antibody Conjugates of
`Doxorubicin Prepared with Branched
`Peptide Linkers: Inhibition of Aggregation by
`Methoxytriethyleneglycol Chains, 45 J. Med. Chem. 4336-
`4343 (2002)
`
`Ex. 2033
`
`Joseph A. Francisco et al., cAC10-vcMMAE, an anti-CD30-
`monomethyl auristatin E conjugate with potent and selective
`antitumor activity, 102(4) Blood 1458-1465 (Aug. 15, 2003)
`
`Ex. 2034
`
`Che-Leung Law et al., Efficient Elimination of B-Lineage
`Lymphomas by Anti-CD20-Auristatin Conjugates, 10 Clin.
`Cancer Res. 7842-7851 (Dec. 1, 2004)
`
`Ex. 2035
`
`157 CONG. REC. S1373 (daily ed. Mar 8, 2011)
`
`Ex. 2036
`
`157 CONG. REC. S1179 (daily ed. Mar. 3, 2011)
`
`Ex. 2037
`
`
`Collection of Judge J. Rodney Gilstrap’s orders granting
`stipulated, unopposed, or patent owner-initiated motions to
`stay after institution of parallel PTAB proceedings.
`
` SF-4844289
`
`xi
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`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2038
`
`
`Ex. 2039
`
`
`Ex. 2040
`
`
`Ex. 2041
`
`
`Ex. 2042
`
`
`Ex. 2043
`
`
`Ex. 2044
`
`
`Ex. 2045
`
`Ex. 2046
`
`Description
`Collection of Judge J. Rodney Gilstrap’s orders granting
`opposed challenger-initiated motions to stay after institution
`of parallel PTAB proceedings.
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 4, 2022), Dkt. 361 (Minutes for Jury
`Selection/Jury Trial Day No. 1 Held Before U.S. District
`Judge Rodney Gilstrap)
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 4, 2022), Dkt. 369 (Verdict Form)
`
`Attorney’s Docket No.: 49223-0019011/1000-00369US,
`Disclaimer Under 35 U.S.C. § 253(A) and 37 C.F.R.
`§ 1.321(A)
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 4-7, 2022), trial transcript excerpts
`addressing written description
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 4-7, 2022), trial transcript excerpts
`addressing enablement
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 4-7, 2022), trial transcript excerpts
`addressing failing to purported failure to particularly point
`out and distinctly claim that which the inventor or a joint
`inventor regards as his or her invention
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 4-7, 2022), trial transcript excerpts
`addressing purported anticipation by Ogitani
`
`Seagen Inc. v. Daiichi Sankyo, Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. April 8, 2022), trial transcript excerpts
`addressing jury instructions
`
` SF-4844289
`
`xii
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2047
`[NEW]
`
`Ex. 2048
`[NEW]
`
`Ex. 2049
`[NEW]
`Ex. 2050
`[NEW]
`
`Ex. 2051
`[NEW]
`
`Ex. 2052
`[NEW[
`Ex. 2053
`[NEW]
`Ex. 2054
`[NEW]
`
`Ex. 2055
`[NEW]
`Ex. 2056
`[NEW]
`
`Description
`Gene M. Dubowchik et al., An acid-cleavable linker stable at
`neutral pH that releases doxorubicin at lysosomal pH,
`Bioorg. Med. Chem. Lett., 3(12) (1993) 2843-2846
`
`Gene M. Dubowchik et al., Doxorubicin Immunoconjugates
`Containing Bivalent, Lysosomally-Cleavable Dipeptide
`Linkages, Bioorg. Med. Chem. Lett., 12(11) (2002) 1529-
`1532
`
`ADCETRIS® (brentuximab vedotin) for Injection, for
`Intravenous use.
`
`Hongsheng Xie et al., Pharmacokinetics and Biodistribution
`of the Antitumor Immunoconjugate, Cantuzumab Mertansine
`(huC242-DM1) and Its Two Components in Mice, J. of
`Pharma. & Experimental Therapeutics, 308(3) (2004) 1073-
`1082
`
`Jason Kantor et al., Antibody Drug Conjugates - Deep dive
`into new technologies and drug candidates, Credit Suisse
`Securities Research & Analytics, May 13, 2014
`
`Seagen Inc. v. Daiichi Sankyo Co., Ltd., No. 2:20-cv-00337-
`JRG (E.D. Tex. Feb. 8, 2021) Dkt. 155
`
`U.S. Patent No. 5,037,883 (Kopecek et al.)
`
`R. Duncan, et al., Anticancer agents coupled to N-(2-
`hydroxypropyl) methacrylamide copolymers. I. Evaluation
`of daunomycin and puromycin conjugates in vitro, Br. J.
`Cancer, 55 (2) (1987) 165-174
`
`Jindřich Kopeček and Ruth Duncan, Targetable Polymeric
`Prodrugs, J. of Controlled Release, 6 (1987) 315-327
`
`D. Putnam and J. Kopecek, Polymer Conjugates with
`Anticancer Activity, Biopolymers II. Advances in Polymer
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`xiii
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2057
`[NEW]
`
`Ex. 2058
`[NEW]
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`Ex. 2062
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`Ex. 2064
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`Ex. 2065
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`Description
`Kazuhiro Inoue, et al., CM-Dextran-Polyalcohol-
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` SF-4844289
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`xiv
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2066
`[NEW]
`
`Ex. 2067
`[NEW]
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`Ex. 2068
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`Ex. 2069
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`Ex. 2071
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`Description
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` SF-4844289
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`xv
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`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2074
`[NEW]
`
`Ex. 2075
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`Ex. 2076
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`Ex. 2077
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`Ex. 2079
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`Ex. 2082
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`Description
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`RESERVED
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`xvi
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`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2083
`[NEW]
`
`Ex. 2084
`[NEW]
`
`Ex. 2085
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`
`Ex. 2086
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`
`Ex. 2087
`[NEW]
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`Ex. 2088
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`
`Ex. 2089
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`Ex. 2090
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`
`Description
`Robert S. Greenfield et al., In Vitro Evaluation of
`Immunoconjugates Prepared by Linking Mitomycin C to
`Monoclonal Antibodies via Polyglutamic Acid Carriers,
`Antibody, Immunoconjugates & Radiopharmaceuticals, 2(3)
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`RESERVED
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`Ex. 2091
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`Paul Wentworth et al., Toward antibody-directed “abzyme”
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` SF-4844289
`
`xvii
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`
`Ex. 2092
`[NEW]
`
`Ex. 2093
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`Ex. 2094
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`
`Ex. 2095
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`Ex. 2096
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`Ex. 2097
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`Ex. 2098
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`Description
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` SF-4844289
`
`xviii
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2099
`[NEW]
`
`Ex. 2100
`[NEW]
`
`Ex. 2101
`[NEW]
`
`Ex. 2102
`[NEW]
`
`Ex. 2103
`[NEW]
`
`Ex. 2104
`[NEW]
`
`Ex. 2105
`[NEW]
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`Ex. 2106
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`Ex. 2107
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` SF-4844289
`
`Description
`Peter D. Senter et al., Anti-tumor effects of antibody-alkaline
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`RESERVED
`
`RESERVED
`
`RESERVED
`
`RESERVED
`
`
`xix
`
`

`

`PGR2021-00030
`
`
`Ex. No.
`Ex. 2108
`[NEW]
`Ex. 2109
`[NEW]
`
`Ex. 2110
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`
`Ex. 2111
`[NEW]
`
`Ex. 2112
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`
`Ex. 2113
`[NEW]
`
`Ex. 2114
`[NEW]
`
`Ex. 2115
`[NEW]
`
`Ex. 2116
`[NEW]
`
` SF-4844289
`
`Description
`John S. Mort et al., Molecules in Focus, Cathepsin B, Int. J.
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`Presentation by Aleix Prat, HER2 metastatic br