Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 1 of 150 PageID #:
`
`13855
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`v.
`
`
`AMGEN INC.,
`
`Defendant and Counterclaim Plaintiff.
`
`v.
`
`SAMSUNG BIOEPIS CO., LTD,
`
`C.A. No. 18-924-CFC
`
`C.A. No. 18-1363-CFC
`
`
`GENENTECH, INC. and CITY OF HOPE, )
`)
`Plaintiffs and Counterclaim Defendants, )
`)
`)
`)
`)
`)
`)
`)
`
`GENENTECH, INC. and CITY OF HOPE, )
`)
`Plaintiffs and Counterclaim Defendants, )
`)
`)
`)
`)
`)
`)
`)
`
`Defendant and Counterclaim Plaintiff.
`
`REVISED JOINT CLAIM CONSTRUCTION BRIEF
`
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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 2 of 150 PageID #:
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`13856
`
`TABLE OF CONTENTS
`
`
`Page
`
`AGREED-UPON CONSTRUCTIONS ..................................................................... 1
`
`DISPUTED CONSTRUCTIONS ............................................................................23
`
`I.
`
`U.S. PATENT NOS. 6,627,196, 7,371,379, AND 10,160,811 ....................... 3
`
`1.
`
`2.
`
`Plaintiffs’ Introduction ................................................................ 3
`
`Defendants’ Introduction ............................................................ 4
`
`A.
`
`“An Initial Dose” (’196 Claims 11, 22; ’379 Claims 11, 21;
`’811 Claims 6, 7) .................................................................................45
`
`1.
`
`2.
`
`Plaintiffs’ Opening Position ......................................................45
`
`Defendants’ Answering Position ..............................................67
`
`a.
`
`Amgen’s Answering Position .........................................67
`
`i.
`
`ii.
`
`“An initial dose” means “the first dose.” .............78
`
`The specification distinguishes between (1)
`“an initial dose” and (2) “initial doses” or
`“series of doses.” .................................................... 9
`
`iii. Amgen’s construction is tied to the asserted
`claims, which cover only the single initial
`dose embodiment. .................................................11
`
`iv.
`
`v.
`
`Claim 16 affirms the distinction between “an
`initial dose” and “plurality of initial doses.” ....1213
`
`Extrinsic evidence confirms Amgen’s
`construction. .....................................................1415
`i
`
`
`
`
`

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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 3 of 150 PageID #:
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`13857
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`vi. Genentech’s construction is unworkable. ............15
`
`b.
`
`Samsung’s Answering Position ......................................16
`
`3.
`
`Plaintiffs’ Reply Position ..........................................................19
`
`a.
`
`Defendants’ Construction Of “An Initial Dose” Is
`Inconsistent With The Intrinsic Evidence. .....................19
`
`i.
`
`ii.
`
`The Intrinsic Record Makes Clear That “An
`Initial Dose” Can Be A Plurality Of Doses. .........20
`
`The Intrinsic Record Does Not Require “An
`Initial Dose” To Be A “First Dose.” ....................23
`
`Extrinsic Evidence Does Not Support Amgen’s
`Construction Of “An Initial Dose.” ............................2425
`
`Defendants’ Arguments Regarding Indefiniteness
`Are Flawed And Premature. ...........................................26
`
`Samsung’s Construction Of “An Initial Dose”
`Impermissibly Narrows The Claims To One
`Embodiment. ...................................................................26
`
`b.
`
`c.
`
`d.
`
`4.
`
`Defendants’ Sur-Reply Position ...............................................27
`
`a.
`
`Amgen’s Sur-Reply Position ..........................................27
`
`i.
`
`ii.
`
`Genentech’s construction ignores the
`specification’s teaching of two distinct
`alternatives ............................................................28
`
`“Initial dose” is synonymous with “first
`dose” .....................................................................30
`
`iii. Genentech did not counter Amgen’s
`extrinsic evidence .............................................3132
`
`iv. Genentech does not address indefiniteness
`
`
`
`ii
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 4 of 150 PageID #:
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`13858
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`problems caused by its construction ....................32
`
`b.
`
`Samsung’s Sur-Reply Position .......................................33
`
`II.
`
`U.S. PATENT NOS. 7,993,834 AND 8,076,066 ..........................................34
`
`1.
`
`2.
`
`Plaintiffs’ Introduction ..............................................................34
`
`Defendants’ Introduction ..........................................................35
`
`A.
`
`“A Method For Increasing Likelihood Of Effectiveness Of
`Breast Cancer Treatment With Humanized Anti-ErbB2
`Antibody huMAb4D5-8” (’834 Claims 2, 5) ..................................3839
`
`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ......................................................39
`
`Defendants’ Answering Position ..............................................40
`
`a.
`
`b.
`
`The preamble of the ’834 patent renders the claims
`indefinite .........................................................................40
`
`Genentech’s proposed construction does not
`resolve indefiniteness .................................................4243
`
`Plaintiffs’ Reply Position ......................................................4344
`
`Defendants’ Sur-Reply Position ...............................................48
`
`B.
`
`“Wherein The Patient’s Cancer Cells Express HER2 At A 0 Or
`1+ Level By Immunohistochemistry” (’066 Claims 2, 6) ..................49
`
`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ..................................................4950
`
`Amgen’s Answering Position ...............................................5152
`
`Plaintiffs’ Reply Position ..........................................................56
`
`Amgen’s Sur-Reply Position ................................................5960
`
`III. U.S. PATENT NO. 8,574,869 ...................................................................6162
`
`
`
`iii
`
`

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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 5 of 150 PageID #:
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`13859
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`1.
`
`2.
`
`Plaintiffs’ Introduction ..........................................................6162
`
`Defendants’ Introduction ......................................................6263
`
`A.
`
`“Following Fermentation” (Claims 5, 8) ............................................63
`
`1.
`
`2.
`
`Plaintiffs’ Opening Position ..................................................6364
`
`Defendants’ Answering Position ..............................................67
`
`a.
`
`b.
`
`Amgen’s Answering Position .....................................6768
`
`Samsung’s Answering Position ......................................72
`
`3.
`
`Plaintiffs’ Reply Position ..........................................................76
`
`a.
`
`b.
`
`Plaintiffs’ Reply to Amgen’s Position ............................76
`
`Plaintiffs’ Reply to Samsung’s Position .....................8081
`
`4.
`
`Defendants’ Sur-Reply Position ...............................................82
`
`a.
`
`b.
`
`Amgen’s Sur-Reply Position ..........................................82
`
`Samsung’s Sur-Reply Position ...................................8384
`
`B.
`
`“Pre-Harvest [Culture Fluid]” (Claims 5, 8) .......................................84
`
`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ..................................................8485
`
`Samsung’s Answering Position ................................................86
`
`Plaintiffs’ Reply Position ..........................................................87
`
`Samsung’s Sur-Reply Position .................................................88
`
`IV. U.S. PATENT NOS. 8,512,983 AND 9,714,293 ......................................8889
`
`1.
`
`2.
`
`Plaintiffs’ Introduction ..........................................................8889
`
`Defendants’ Introduction ..........................................................90
`iv
`
`
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`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 6 of 150 PageID #:
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`13860
`
`A.
`
`“A Glutamine-Free Production Culture Medium” (’983 Claims
`2, 19; ’293 Claims 72, 73) ...................................................................91
`
`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ......................................................91
`
`Defendants’ Answering Position ..............................................95
`
`Plaintiffs’ Reply Position ........................................................102
`
`Defendants’ Sur-Reply Position .............................................110
`
`V. U.S. Patent No. 7,485,704 PATENT ...........................................................113
`
`A.
`
`“About 18°C” (Claims 6, 12) ............................................................113
`
`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ....................................................113
`
`Samsung’s Answering Position ..............................................117
`
`Plaintiffs’ Reply Position ........................................................118
`
`Samsung’s Sur-Reply Position ...............................................120
`
`B.
`
`“Performing Subsequent Purification Of Compositions
`Comprising Said Protein By Protein A Affinity
`Chromatography At A [Temperature Range]” (Claims 6, 12) .........120
`
`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ....................................................120
`
`Samsung’s Answering Position ..............................................122
`
`Plaintiffs’ Reply Position ........................................................122
`
`Samsung’s Sur-Reply Position ...............................................123
`
`VI. U.S. PATENT NO. 7,390,660 .....................................................................123
`
`A.
`
`“Wherein Said Citric Acid Or Citrate Is Maintained At A
`Concentration Of About 1 To 50 mmol/L During Cultivation”
`And “Is Not Bound In A Chelate Complex With Iron Or
`Another Transition Metal Ion” (Claim 3, 6) .....................................123
`v
`
`
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`

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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 7 of 150 PageID #:
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`13861
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`1.
`
`2.
`
`3.
`
`4.
`
`Plaintiffs’ Opening Position ....................................................124
`
`Samsung’s Answering Position ..............................................127
`
`a.
`
`b.
`
`“not bound” ...................................................................127
`
`“about 1 to 50 mmol/l” .................................................129
`
`Plaintiffs’ Reply Position ........................................................130
`
`Samsung’s Sur-Reply Position ...............................................133
`
`a.
`
`b.
`
`“not bound” ...................................................................133
`
`“about 1 to 50 mmol/l” .................................................134
`
`
`
`
`
`vi
`
`
`
`
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 8 of 150 PageID #:
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`13862
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Abtox, Inc. v. Exitron Corp.,
`122 F.3d 1019 (Fed. Cir. 1997), opinion amended on reh’g, 131
`F.3d 1009 (Fed. Cir. 1997) ................................................................................. 12
`Alfred E. Mann Found. for Sci. Research v. Cochlear Corp.,
`841 F.3d 1334 (Fed. Cir. 2016) ........................................................... 5960, 60 61
`Allergan Sales, LLC v. Lupin Ltd.,
`2013 WL 4519609 (E.D. Tex. Aug. 21, 2013) ................................................... 31
`Astrazeneca AB, Aktiebolaget Hassle, KBI-E, Inc. v. Mut. Pharm. Co.,
`384 F.3d 1333 (Fed. Cir. 2004) ................................................................ 2021, 29
`August Tech. Corp. v. Camtek, Ltd.,
`655 F.3d 1278 (Fed. Cir. 2011) .......................................................... 1314, 22, 29
`Baran v. Med. Device Techs., Inc.,
`616 F.3d 1309 (Fed. Cir. 2010) .................................................................... 29, 30
`Berkheimer v. HP Inc.,
`881 F.3d 1360 (Fed. Cir. 2018) ................................................................ 41, 4344
`Biogen Idec, Inc. v. GlaxoSmithKline LLC,
`713 F.3d 1090 (Fed. Cir. 2013) ..................................................70, 129, 133, 134
`Boston Sci. Corp. v. Cook Inc.,
`187 F. Supp. 3d 249, 275-76 (D. Mass. 2016) ............................................................ 1516
`C.R. Bard, Inc. v. U.S. Surgical Corp.,
`388 F.3d 858 (Fed. Cir. 2004) ............................................................. 1718, 72 73
`CAE Screenplates Inc. v. Heinrich Fiedler GmbH,
`224 F.3d 1308 (Fed. Cir. 2000) .......................................................................... 51
`Chicago Bd. Options Exch., Inc. v. Int’l Sec. Exch., LLC,
`677 F.3d 1361 (Fed. Cir. 2012) .................................................................... 57, 60
`vii
`
`
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 9 of 150 PageID #:
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`13863
`
`Convolve, Inc. v. Compaq Computer Corp.,
`812 F.3d 1313 (Fed. Cir. 2016) .............................................................. 12, 13, 22
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) ...................................................................................... 114
`Datamize, LLC v. Plumtree Software, Inc.,
`417 F.3d 1342 (Fed. Cir. 2005) .......................................................................... 71
`Depomed, Inc. v. Purdue Pharma L.P.,
`No. 13-571 (MLC)(TJB), 2017 WL 1319818 (D.N.J. Apr. 6, 2017) ................ 1516
`Desenberg v. Google, Inc.,
`392 F. App’x 868 (Fed. Cir. 2010) ...................................................... 5455, 60 61
`Ecolab, Inc. v. FMC Corp.,
`569 F.3d 1335 (Fed. Cir. 2009) ................................................................ 132, 134
`Ferring B.V. v. Watson Labs., Inc.-Fla.,
`764 F.3d 1382 (Fed. Cir. 2014) ................................................................ 115, 125
`Geneva Pharm., Inc. v. GlaxoSmithKline PLC,
`349 F.3d 1373 (Fed. Cir. 2003) ........................................................................................ 7576
`GPNE Corp. v. Apple Inc.,
`830 F.3d 1365 (Fed. Cir. 2016) .......................................................................... 60
`Haemonetics Corp. v. Baxter Healthcare Corp.,
`607 F.3d 776 (Fed. Cir. 2010) ...................................................................... 13, 22
`Halliburton Energy Servs., Inc. v. M-I LLC,
`514 F.3d 1244 (Fed. Cir. 2008) ........................................................................................ 7576
`Int’l Test Sols., Inc. v. Mipox Int’l Corp.,
`No. 16-cv-00791-RS, 2017 WL 1367975 (N.D. Cal. Apr. 10, 2017) ................ 41
`Interval Licensing LLC v. AOL, Inc.,
`766 F.3d 1364 (Fed. Cir. 2014) .......................................................... 46, 4847, 49
`Karlin Tech. Inc. v. Surgical Dynamics, Inc.,
`177 F.3d 968 (Fed. Cir. 1999) .......................................................... 20, 23, 30, 31
`
`
`
`viii
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 10 of 150 PageID #:
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`13864
`
`Kustom Signals, Inc. v. Applied Concepts, Inc.,
`264 F.3d 1326 (Fed. Cir. 2001) ................................................................ 1011, 22
`Liberty Ammunition, Inc. v. United States,
`835 F.3d 1388 (Fed. Cir. 2016) ................................................................ 41, 4344
`Mantech Envtl. Corp. v. Hudson Envtl. Servs., Inc.,
`152 F.3d 1368 (Fed. Cir. 1998) .......................................................................... 55
`Meds. Co. v. Mylan, Inc.,
`853 F.3d 1296 (Fed. Cir. 2017) .......................................................................... 32
`Multiform Desiccants, Inc. v. Medzam, Ltd.,
`133 F.3d 1473 (Fed. Cir. 1998) ........................................................................................ 5556
`Norian Corp. v. Stryker Corp.,
`432 F.3d 1356 (Fed. Cir. 2005) .......................................................................... 12
`Nystrom v. TREX Co.,
`424 F.3d 1136 (Fed. Cir. 2005) .......................................................................... 56
`Omega Eng’g, Inc. v. Raytek Corp.,
`334 F.3d 1314 (Fed. Cir. 2003) ........................................................................................ 5354
`Pall Corp. v. Micron Separations, Inc.,
`66 F.3d 1211 (Fed. Cir. 1995) .......................................................................... 115
`Perfect Surgical Techniques, Inc. v. Olympus Am., Inc.,
`841 F.3d 1004 (Fed. Cir. 2016) .......................................................................... 11
`Pharmastem Therapeutics, Inc. v. Viacell, Inc.,
`No. 02-148-GMS, 2003 WL 124149 (D. Del. Jan. 13, 2003) ............................ 26
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .......................................................... 105106, 109
`Poly-Am., L.P. v. API Indus., Inc.,
`839 F.3d 1131 (Fed. Cir. 2016) .................................................................. 81, 109
`Rexnord Corp. v. Laitram Corp.,
`274 F.3d 1336 (Fed. Cir. 2001) ........................................................... 1920, 28 29
`
`
`
`ix
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 11 of 150 PageID #:
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`13865
`
`Route1 Inc. v. AirWatch LLC,
`2018 WL 3574873 (D. Del. July 25, 2018) ........................................................ 29
`Saffran v. Johnson & Johnson,
`712 F.3d 549 (Fed. Cir. 2013) .......................................................................... 134
`SkinMedica, Inc. v. Histogen Inc.,
`727 F.3d 1187 (Fed. Cir. 2013) .................................................................... 10, 22
`Telcordia Techs., Inc. v. Cisco Sys., Inc.,
`612 F.3d 1365 (Fed. Cir. 2010) .......................................................................... 99
`Texas Instruments Inc. v. ITC,
`988 F.2d 1165 (Fed. Cir. 1993) .......................................................................... 51
`Thorner v. Sony Comput. Entm’t Am. LLC,
`669 F.3d 1362 (Fed. Cir. 2012) .......................................................................... 29
`TIP Systems, LLC v. Phillips & Brooks/Gladwin, Inc.,
`529 F.3d 1364 (Fed. Cir. 2008) ........................................................................ 128
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996) .......................................................................... 103
`Wasica Fin. GmbH v. Cont’l Auto. Sys., Inc.,
`853 F.3d 1272 (Fed. Cir. 2017) ........................................................ 10, 22, 28, 29
`
`
`
`
`x
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 12 of 150 PageID #:
`
`13866
`
`Pursuant to the Court’s Scheduling Order in the above-captioned cases,
`
`Plaintiffs Genentech, Inc. and City of Hope (“Plaintiffs”) and Defendants Amgen
`
`Inc. (“Amgen”) and Samsung Bioepis Co., Ltd. (“Samsung” and collectively with
`
`Amgen, “Defendants”) submit the following Joint Claim Construction Brief.
`
`AGREED-UPON CONSTRUCTIONS
`
`The chart below sets forth the terms and agreed-upon constructions for the
`
`Agreed-Upon Construction
`wherein the breast cancer cells from
`the human subject have been found
`to express ErbB2 protein at a 0 or
`1+ level by any
`immunohistochemistry test
`
`The preamble is limiting
`
`patents asserted in these litigations.
`
`Claim Term and Claim
`“wherein the breast cancer cells from the
`human subject have been found to have a
`0 or 1+ score of ErbB2 protein expression
`by immunohistochemistry”
`
`U.S. Patent No. 7,993,834, Claims 2, 5
`
`“A method of identifying and treating a
`breast cancer patient disposed to respond
`favorably to a HER2 antibody,
`huMAb4D5-8”
`
`U.S. Patent No. 8,076,066, Claims 2, 6
`
`
`
`
`
`1
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 13 of 150 PageID #:
`
`13867
`
`Agreed-Upon Construction
`The preamble is limiting
`
`bubbling of a gas into a liquid
`
`
`culture fluid that has been harvested
`
`eluting the mixture starting at a first
`concentration between 0 and 1 M of
`an elution salt and ending at a
`second higher concentration
`between 0 and 1 M of the elution
`salt
`
`The preamble is limiting
`
`The preamble is limiting
`
`Claim Term and Claim
`“A method for the prevention of the
`reduction of a disulfide bond in an
`antibody expressed in a recombinant host
`cell”
`
`U.S. Patent No. 8,574,869, Claims 5, 8
`
`“sparging”
`
`U.S. Patent No. 8,574,869, Claims 5, 8
`
`“harvested culture fluid”
`
`U.S. Patent No. 8,574,869, Claims 5, 8
`
`“eluting the mixture at a gradient of about
`0-1 M of an elution salt”
`
`U.S. Patent No. 6,620,918, Claims 5, 7
`
`“A method for reducing glucose
`consumption during cultivation”
`
`U.S. Patent No. 7,390,660, Claim 3
`
`“A method for reducing lactate production
`during cultivation”
`
`U.S. Patent No. 7,390,660, Claim 6
`
`
`
`
`
`
`2
`
`
`
`
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 14 of 150 PageID #:
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`13868
`
`DISPUTED CONSTRUCTIONS
`
`The parties’ respective positions on disputed claim terms are set forth below.
`
`In view of the settlement and dismissal of Genentech, Inc. v. Celltrion, Inc., No. 18-
`
`cv-95-CFC (consolidated), certain disputed claim terms specific to that case that
`
`were addressed in the Joint Claim Construction Chart are no longer at issue. In
`
`addition, subsequent to submitting the Joint Claim Construction Chart, the parties
`
`have agreed upon a claim construction for the term “wherein the breast cancer cells
`
`from the human subject have been found to have a 0 or 1+ score of ErbB2 protein
`
`expression by immunohistochemistry” in U.S. Patent No. 7,993,834, as reflected
`
`above.
`
`I.
`
`U.S. PATENT NOS. 6,627,196, 7,371,379, AND 10,160,811
`1.
`
`Plaintiffs’ Introduction
`
`Trastuzumab, the active ingredient in Genentech’s drug Herceptin, was
`
`initially approved by the FDA in August 1998 with a weekly dosing regimen. The
`
`’196, ’379, and ’811 method-of-treatment patents reflect the further discovery that
`
`trastuzumab could be administered less frequently without compromising safety or
`
`
`
`3
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 15 of 150 PageID #:
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`13869
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`efficacy. JA00000012(’196 patent,1 6:20-31).2 In particular, the patents teach how
`
`to administer the drug in ways that allow for longer intervals between doses while
`
`still maintaining efficacy. JA00000012(6:31-46); JA00000026(34:20-23). For
`
`example, claim 7 of the ’811 patent recites a method of administering an initial dose
`
`of 8 mg/kg trastuzumab followed by subsequent doses of 6 mg/kg every three weeks.
`
`JA00005411(57:51-38).
`
`2.
`
`Defendants’ Introduction
`
`These “Dosing Patents” share a specification and describe methods of treating
`
`cancer using an anti-ErbB2 antibody, such as trastuzumab (Herceptin), using a
`
`schedule involving an initial dose followed by maintenance doses administered less
`
`frequently than weekly. Before the original application was filed in August 1999,
`
`trastuzumab was FDA-approved and marketed for administration using an initial
`
`dose of 4 mg/kg followed by weekly maintenance doses of 2 mg/kg. Declaration of
`
`Michelle S. Rhyu in Support of Defendants’ Claim Construction Brief (“Rhyu
`
`Decl.”) Ex. 1 (Herceptin 1998 Label).3
`
`
`1
`The ’196, ’379, and ’811 patents contain identical disclosures. For
`convenience, Plaintiffs cite to the ’196 specification.
`
`“JA000000___” refers to the Joint Claim Construction Chart Appendix C.
`2
`18-cv-924, D.I. 60; 18-cv-1363, D.I. 48.
`
`Although the Herceptin 1998 Label was included in the intrinsic record (file
`4
`
`3
`
`
`
`

`

`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 16 of 150 PageID #:
`
`13870
`
`A.
`
`“An Initial Dose” (’196 Claims 11, 22; ’379 Claims 11, 21; ’811
`Claims 6, 7)
`
`Plaintiffs’ Proposal
`Initial single dose or
`initial series of doses
`
`Amgen’s Proposal
`The first dose of the
`claimed antibody given
`to the patient as part of a
`treatment regimen
`
`
`
`1.
`
`Plaintiffs’ Opening Position
`
`The parties have two key disputes:
`
`Samsung’s Proposal
`The first dose of the
`claimed antibody given
`to the patient as part of a
`treatment regimen, also
`known as the loading
`dose
`
`1.
`
`Can “an initial dose” be a series of doses or a single dose as
`
`Plaintiffs propose, or must it be a single dose as Defendants
`
`propose?
`
`2.
`
`Is “an initial dose” necessarily a “loading dose” as only Samsung
`
`contends?
`
`Each of these disputes should be resolved in Plaintiffs’ favor.
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`First, the claim language of the ’196 patent confirms that “an initial dose” can
`
`include more than one dose, i.e., a series of doses. Specifically, claim 16 of the ’196
`
`patent recites “administering to the patient an initial dose of the antibody, wherein
`
`the initial dose is a plurality of doses.” JA00000038. A “plurality of doses” is more
`
`
`history of the ʼ811 patent), a clean copy is provided as Rhyu Ex. 1 because the copy
`in the file history is not legible.
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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 17 of 150 PageID #:
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`than one dose, which is reflected in Plaintiffs’ construction. In comparison,
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`Defendants’ proposed construction is irreconcilable with how “an initial dose” is
`
`used in the claims themselves, since their construction excludes a plurality of doses.
`
`Moreover, consistent with claim 16’s recitation of a “plurality of doses,” the
`
`patentee defined “an initial dose” to include a “series of doses.” For example, the
`
`specification states that “[t]he initial dose may be one or more administrations of
`
`drug.” JA00000011(4:56-60). The specification also describes embodiments
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`“[w]here the initial dose is a series of doses.” JA00000019(19:34-37). See also
`
`JA00000031(44:57-65) (“[T]he front loading initial dose is a series of intravenous
`
`or subcutaneous injections….”). To encompass the full scope of the term as used in
`
`the patents’ claims and specification, the term “an initial dose” should be construed
`
`to encompass either a single dose or a series of doses.
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`Second, no evidence supports limiting “an initial dose” to a “loading dose,”
`
`as proposed by Samsung (and no other party). “An initial dose” can be a loading
`
`dose, which the specification defines as “an initially higher dose followed by the
`
`same or lower doses at intervals.” JA00000019(19:19-21). But the specification
`
`also makes clear that “an initial dose” need not be a “loading dose”—for example,
`
`where the initial dose amount is lower than the subsequent dose amounts.
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`JA00000031(44:57-65) (total initial dose of more than 4 mg/kg, subsequent doses
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`of 6 mg/kg); JA00000012(5:40-43) (initial dose series of 1 mg/kg a day for three
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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 18 of 150 PageID #:
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`days, subsequent doses of 6 mg/kg). In short, the intrinsic record provides no basis
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`to read the separate concept of a “loading dose” into this claim term. Accordingly,
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`the Court should reject Samsung’s attempt to narrow the claims by requiring that an
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`“initial dose” always be a “loading dose.”
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`2.
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`Defendants’ Answering Position
`a.
`
`Amgen’s Answering Position
`
`Amgen asserts that “an initial dose” means “the first dose” as opposed to a
`
`series of doses. Genentech’s construction is inconsistent with the intrinsic evidence
`
`and the common use of this term by a POSA. To a POSA, “an initial dose” means
`
`a single first dose given to a patient who is beginning new treatment. This first dose
`
`is distinct from subsequent doses because the initial dose is given with the goal of
`
`establishing an efficacious level of the drug in the patient, while subsequent doses
`
`are designed to maintain that level.
`
`The claims and specification repeatedly distinguish treatment regimens
`
`having a single initial dose from those having a series of initial doses. Claim 1 and
`
`its dependent claims cover only the single initial dose embodiment, while claim 16
`
`covers the alternative series of initial doses. Genentech’s insistence that “an initial
`
`dose” must have the same meaning in claims 1 and 16 ignores case law. Where, as
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`here, the specification and claims provide distinct alternative embodiments of a term,
`
`it is proper to construe claim 1 as the single initial dose embodiment and claim 16
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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 19 of 150 PageID #:
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`as the embodiment requiring a series of doses. Finally, Genentech’s construction is
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`indefinite, because it destroys any distinction between the “initial dose” and
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`“subsequent doses” recited in the claims.
`
`i.
`
`“An initial dose” means “the first dose.”
`
`The plain and ordinary meaning of “an initial dose,” consistent with the
`
`teachings of the specification, is a single first dose given to a patient as part of a
`
`treatment regimen. Declaration of John A. Glaspy, M.D. (“Glaspy”) ¶¶33-36,
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`44¶¶33-34. Consistent with this, the specification uses “first dose” synonymously
`
`with “an initial dose.” See also Glaspy ¶36.
`
`JA00000012(6:54-61)
`
`JA00000012(6:22-28)
`
`“the invention provides a method for the
`treatment of cancer in a human patient
`… comprising administering to the
`patient an initial dose of at least
`approximately 5 mg/kg of the anti-ErbB
`antibody; and administering to the
`patient a plurality of subsequent doses
`of the antibody ….” (emphasis added)
`
`“[T]he invention provides a method for
`the treatment of cancer … comprising
`administering to the patient first dose of
`an anti-ErbB2 antibody followed by at
`least one subsequent dose of
`the
`antibody ….”
`
`Other intrinsic evidence also uses “initial” to mean “first.” For example, the
`
`prior art 1998 Herceptin label refers to the first 4 mg/kg dose as “the initial loading
`
`dose.” Rhyu Decl. Ex. 1 (Herceptin 1998 Label)34; Glaspy ¶¶28-29, 34¶28. Indeed,
`
`
`34 This usage persists in the current Herceptin label. Rhyu Decl. Ex. 3 (Herceptin
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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 20 of 150 PageID #:
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`13874
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`the specification and file history both refer to the 4 mg/kg administered in the prior
`
`art dosing regimen as the initial loading dose. See JA00000011(3:61-65) (“The
`
`recommended initial loading dose for HERCEPTIN® is 4 mg/kg .… [t]he
`
`recommended weekly maintenance dose is 2 mg/kg .…”) (emphasis added); see also
`
`JA00000697; see also Glaspy ¶¶28-29JA00000734 (“Each patient received a
`
`loading dose of 250 mg of rhuMAb HER2 on day 0, 34and beginning on day 7, 100
`
`mg weekly for a total of 10 doses.”).
`
`ii.
`
`The specification distinguishes between (1) “an
`initial dose” and (2) “initial doses” or “series of
`doses.”
`
`Dosing regimens in which the initial dose is given to the patient as a single
`
`administration are described throughout the specification. But the specification also
`
`describes regimens in which the initial dose is divided into a series of doses. For
`
`example, where a clinician might be concerned that a single large initial dose could
`
`be toxic, the initial dose might be administered as a series of smaller doses given in
`
`succession. See, e.g., JA00000012(5:40-44) (“In another embodiment, the invention
`
`includes initial doses . . . on each of days 1, 2 and 3 .…”); see also Glaspy ¶40.
`
`Critically for the dispute here, the specification consistently uses the
`
`disjunctive term “or” to distinguish a single initial dose from a series of initial doses:
`
`
`2018 Label).
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`Case 1:18-cv-01363-CFC Document 105 Filed 04/15/19 Page 21 of 150 PageID #:
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`“The present invention concerns the discovery that an early attainment
`of an efficacious target trough serum concentration by providing an
`initial dose or doses of anti-ErbB2 antibodies followed by subsequent
`doses of equal or smaller amounts of antibody (greater front loading) is
`more efficacious than conventional treatments.”
`JA00000011(4:21-26) (emphasis added). This usage pervades the patent:
`
`“[a]ccording to the present invention, front loading is achieved by an initial dose or
`
`doses delivered over three weeks or less that causes the animal’s or patient’s serum
`
`concentration to reach a target serum trough concentration. Preferably, the initial
`
`front loading dose or series of doses.” JA00000019(19:24-29) (emphasis added); see
`
`also JA00000011(4:38-40 (“Preferably, the initial dose (or doses) as well