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`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF WEST VIRGINIA
`
`REGENERON PHARMACEUTICALS, INC.,
`
`Plaintiff,
`
`v.
`
`MYLAN PHARMACEUTICALS INC.,
`
`Defendant.
`
`Case No. 1:22-cv-00061-TSK
`
`OUTSIDE COUNSEL EYES ONLY
`
`FILED UNDER SEAL
`
`DEFENDANT MYLAN PHARMACEUTICALS INC.’S REPLY MEMORANDUM
`IN SUPPORT OF MYLAN’S MOTION FOR SUMMARY JUDGMENT
`
`

`

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`TABLE OF CONTENTS
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`TABLE OF AUTHORITIES ......................................................................................................... iii
`
`TABLE OF ABREVIATIONS ....................................................................................................... v
`
`TABLE OF RECORD CITATIONS ........................................................................................... viii
`
`I.
`
`II.
`
`INTRODUCTION. ............................................................................................................. 1
`
`CLAIM 18 OF THE ‘865 PATENT SAYS, “DOES NOT CONTAIN
`PHOSPHATE” WITHOUT EQUIVOCATION; REGENERON DOES NOT
`DISPUTE THAT PHOSPHATE EXISTS IN THE ACCUSED YESAFILITM
`PRODUCT. ......................................................................................................................... 1
`
`A.
`
`The record nowhere supports Regeneron’s new claim construction that the
`‘865 patent’s “formulation” differs from the contents of the vial. ......................... 2
`
`1.
`
`2.
`
`A new “formulation” claim construction is unnecessary and
`untimely. ..................................................................................................... 2
`
`The component list is not a representation that no other compounds
`exist in the listed components. .................................................................... 4
`
`B.
`
`C.
`
`D.
`
`Regeneron’s effort to distinguish between “purposeful” excipients and
`“unwanted” impurities also fails. ............................................................................ 5
`
`“Does not contain phosphate” should not be construed to have the same
`meaning as “consisting of” to exclude phosphate “impurities.” ............................. 7
`
`The component list in the Summary Table is not a “specification” under
`the FDA regulations for purposes of Sunovion. ...................................................... 7
`
`III. MYLAN SHOULD RECEIVE SUMMARY JUDGMENT ON THE
`REMAINING DOSING PATENT ISSUES. ...................................................................... 9
`
`A.
`
`B.
`
`C.
`
`Regeneron concedes it will not assert direct infringement by Mylan. .................... 9
`
`The ‘601 patent. ...................................................................................................... 9
`
`Regeneron must be clear that it will not dispute for trial that the “visual
`acuity” elements in claims 1 and 16 of the ‘572 patent lack patentable
`weight. ..................................................................................................................... 9
`
`1.
`
`Regeneron must clearly confirm the 52-week visual acuity
`language of claims 1 and 16 lacks patentable weight via the
`Court’s construction. ................................................................................. 10
`
`i
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`

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`49413
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`2.
`
`If the 52-week visual acuity language of claims 1 and 16 has
`patentable weight, then Regeneron cannot meet its burden of proof. ....... 10
`
`a.
`
`b.
`
`Regeneron fails in its burden on divided infringement. ................ 10
`
`Regeneron fails in its burden on induced infringement. ............... 11
`
`D.
`
`Claim elements to DME, or “isotonic solution” and “nonionic surfactant”
`formulation, cannot salvage the claims’ validity. ................................................. 14
`
`IV.
`
`CONCLUSION. ................................................................................................................ 15
`
`ii
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`

`

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`TABLE OF AUTHORITIES
`
`Cases
`
`AstraZeneca LP v. Apotex, Inc.,
`633 F.3d 1042 (Fed. Cir. 2010) ................................................................................................ 13
`
`Aventis Pharma Deutschland GmbH v. Lupin Ltd.,
`No. CIV.A. 2:05CV421, 2006 WL 1314413 (E.D. Va. May 11, 2006) ..................................... 7
`
`Bayer AG v. Elan Pharmaceutical Research Corp.,
`212 F.3d 1241 (Fed. Cir. 2000) .................................................................................................. 8
`
`Conoco, Inc. v. Energy & Environmental Intern., L.C.,
`460 F.3d 1349 (Fed. Cir. 2006) .......................................................................................... 5, 6, 7
`
`DSW, Inc. v. Shoe Pavilion, Inc.,
`537 F.3d 1342 (Fed. Cir. 2008) .................................................................................................. 6
`
`Ericsson, Inc. v. D-Link Sys., Inc.,
`773 F.3d 1201 (Fed. Cir. 2014) .......................................................................................... 11, 14
`
`Glaxo Group Ltd. v. Apotex, Inc.,
`376 F.3d 1339 (Fed. Cir. 2004) .................................................................................................. 6
`
`Glaxo, Inc. v. Novopharm, Ltd.,
`110 F.3d 1562 (1997) .................................................................................................................. 2
`
`GlaxoSmithKline v. Teva,
`7 F.4th 1320 (Fed. Cir. 2021) ................................................................................................... 13
`
`HZNP Medicines LLC v. Actavis Laboratories UT, Inc.,
`940 F.3d 680 (Fed. Cir. 2019) .................................................................................................. 12
`
`Otsuka Pharm. Co. v. Lupin Ltd.,
`2022 WL 2952759 (D. Del. July 26, 2002) ............................................................................ 5, 6
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .................................................................................................. 3
`
`Shire LLC v. Amneal Pharms., LLC,
` No. CIV.A. 11-3781 SRC, 2014 WL 2861430 (D.N.J. June 23, 2014) .................................. 11
`
`Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc.,
`731 F.3d 1271 (Fed. Cir. 2013) .......................................................................................... 2, 7, 8
`
`Warner-Lambert Co. v. Apotex Corp.,
`316 F.3d 1348 (Fed. Cir. 2003) .......................................................................................... 11, 12
`
`iii
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`

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`49415
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`Statutes
`
`35 U.S.C. § 271(b) ........................................................................................................................ 11
`
`42 U.S.C. § 262(i)(3) .................................................................................................................... 13
`
`42 U.S.C. § 262(k) ........................................................................................................................ 13
`Regulations
`
`21 C.F.R. § 314.50(d)(1)(i) ............................................................................................................. 8
`
`21 C.F.R. § 320.33 ........................................................................................................................ 13
`
`iv
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`49418
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`49419
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`49420
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`7), to discount phosphates within these same components or excipients. This has the same
`
`infirmities as above;
`
`
`
` (See Section II.B). Regeneron urges construing “does not contain
`
`phosphate” as “consisting of,” to ignore
`
` (Dkt. 443,
`
`Reg. Opp. at 8). Regeneron could have, but didn’t, use “consisting of” claim language, and it can’t
`
`rewrite its claims now. (See Section II.C).
`
`Regeneron also proposes that the summary component list it relies on is akin to a legally
`
`binding “specification” under Sunovion Pharm., Inc. v. Teva Pharm. USA, Inc., 731 F.3d 1271
`
`(Fed. Cir. 2013). It isn’t, rendering its last theory a failure as well. (See Section II.D).
`
`Since Regeneron’s arguments are ultimately legal, and not factual, summary judgment for
`
`Mylan on claim 18 is proper, as discussed in more detail below.
`
`A.
`
`The record nowhere supports Regeneron’s new claim construction that the
`‘865 patent’s “formulation” differs from the contents of the vial.
`
`1.
`
`A new “formulation” claim construction is unnecessary and untimely.
`
`Regeneron states that whether YESAFILITM, when sold, has phosphate is the “wrong
`
`question.” (Dkt. 443, Reg. Opp. at 5). But that is the only relevant question. For a product under
`
`pending FDA review, “[w]hat is likely to be sold, or, preferably, what will be sold, will ultimately
`
`determine whether infringement exists.” Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562, 1570
`
`(Fed. Cir. 1997). Regeneron admits that it never tested the product accused of infringement for
`
`which FDA approval is sought—YESAFILITM—to determine whether it contains phosphate.
`
`(Dkt. 443-1, Reg. SMF Resp. ¶ 23). That justifies summary judgment for Mylan.
`
`Though claim 18 requires the “vial of claim 5, wherein said formulation does not contain
`
`phosphate,” (Dkt. 443-1, Reg. SMF Resp. ¶ 17), Regeneron seeks a new “formulation”
`
`construction that means a component list, not the product in the vial; so that Regeneron can look
`
`2
`
`

`

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`only at what it calls the “operative document governing the infringement inquiry,” to the exclusion
`
`of the product to be sold. (Dkt. 443, Reg. Opp. at 5-6).
`
`First, the ‘865 patent does not limit the term “formulation” to a component list—it uses
`
`“formulation” broadly, including to describe the contents of a vial for intravitreal injection into the
`
`eye. (See Dkt. 432-16, ‘865 patent at Abstract (“Ophthalmic formulations” of the drug “are
`
`provided suitable for intravitreal administration to the eye”); id. at col. 1, ll. 45-46 (same); id. at
`
`col. 5, ll. 23-25 (“The invention further features ophthalmic formulations provided in a pre-filled
`
`syringe or vial, particularly suitable for intravitreal administration”)). Regeneron’s new claim
`
`construction cannot be right, because it directly conflicts with the intrinsic record. Phillips v. AWH
`
`Corp., 415 F.3d 1303, 1324 (Fed. Cir. 2005) (en banc) (noting that a court’s construction may not
`
`“contradict claim meaning that is unambiguous in light of the intrinsic evidence”).
`
`Second, Regeneron did not limit the term “formulation” this way in its prior discovery
`
`responses, infringement contentions, or expert reports—it instead applied the “formulation” term
`
`to mean the substance injected into the eye. (Dkt. 432-30, Regeneron’s Responses to Mylan’s
`
`Interrogatories at No. 2 (in “developing the drug product formulation for EYLEA—it sought to
`
`develop a formulation that stabilized aflibercept and that was suitable for intravitreal injection”);
`
`Ex. 28, Regeneron ‘865 Contentions at 4 (alleging YESAFILITM is a “formulation” because it “is
`
`being developed as a biosimilar product to Eylea®” and is a “sterile solution intended for
`
`intravitreal administration supplied in a single-use vial”); 25 (same)); Dkt. 432-17, Trout Opening
`
`¶ 49 (“M710 comprises ‘an ophthalmic formulation suitable for intravitreal injection’ because it is
`
`‘a sterile solution intended for intravitreal administration.’”) (emphasis in original)).
`
`
`
`
`
`3
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`

`

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`
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`Thus, Regeneron has no basis to limit the term “formulation” to just a component list.
`
`2.
`
`The component list is not a representation that no other compounds
`exist in the listed components.
`
`Even assuming that Regeneron’s proffered summary table,
`
`
`
`
`
`
`
`
`
`
`
` (Dkt. 443, Reg. Opp. at 6). That is a strawman choice,
`
`and wrong.
`
`By name and nature, the Summary Table is an “overview” of the top-line ingredients in
`
`YESAFILITM (denoted as M710 DP) and Regeneron’s Eylea®. FDA does not stop its review at
`
`the Summary Table. FDA comprehensively analyzes each component.
`
`
`
`
`
`
`
`1 Regeneron calls this the “operative document,” but it is not the same one cited in its contentions
`and in Dr. Trout’s expert report to describe formulation ingredients. (Ex. 28, Regeneron ‘865
`Contentions at 5-6; Dkt. 432-17, Trout Opening ¶ 42). Mylan nevertheless uses it here.
`
`4
`
`

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`49424
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`
` Regeneron did not craft claim 18 to say the
`
`formulation does not contain “phosphate buffers,” “high phosphate levels,” or “intentional
`
`phosphate.” Regeneron used clear and unequivocal “does not contain phosphate” language that
`
`excludes phosphate, of any kind, source, amount, or purpose. Regeneron may regret this today,
`
`but how patentees claim their invention is the claim drafter’s choice and the Federal Circuit “has
`
`consistently adhered to the proposition that courts cannot alter what the patentee has chosen to
`
`claim as his invention.” DSW, Inc. v. Shoe Pavilion, Inc., 537 F.3d 1342, 1347 (Fed. Cir. 2008).
`
`Regeneron insists that it can construe “does not contain phosphate” to mean, does not
`
`contain intentionally-added phosphates, under Glaxo Grp. Ltd. v. Apotex, Inc., 376 F.3d 1339 (Fed.
`
`Cir. 2004). (Dkt. 443, Reg. Opp. at 7). Not so. In Glaxo, the claims required cefuroxime axetil
`
`with “a purity of at least 95% aside from residual solvents.” Id. at 1343. The excipients-versus-
`
`impurities debate arose because Apotex argued it could avoid the claimed cefuroxime axetil purity
`
`limit by co-precipitating cefuroxime axetil with zinc salts, which then rendered the drug only 90%
`
`“pure.” Id. at 1343, 1346. The Federal Circuit focused on the zinc salt’s purpose because the
`
`specification defined an impurity as “an unwanted reaction product formed during synthesis.” Id.
`
`at 1347. Apotex purposefully adding zinc salts “to enhance the performance” of the drug plainly
`
`could not meet the specification’s “unwanted” impurity definition. Id. The Federal Circuit never
`
`suggested the zinc salts, or impurities in cefuroxime axetil, were not part of the formulation. Thus,
`
`Glaxo does not justify limiting the scope of claim 18 phosphates so it can cover YESAFILITM.
`
`Nor does Conoco, 460 F.3d at 1360; or Otsuka, 2022 WL 2952759 at *3, help Regeneron. As next
`
`discussed, both cases’ claims used “consisting of,” not “does not contain phosphate” like claim 18,
`
`6
`
`

`

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`which also changes the analysis.
`
`C.
`
`“Does not contain phosphate” should not be construed to have the same
`meaning as “consisting of” to exclude phosphate “impurities.”
`
`Regeneron’s next claim construction argument is that 1) “does not contain phosphate” is a
`
`“closed” term analogous to “consisting of”; 2) the latter phrase can avoid impurities; thus, 3)
`
` (Dkt.
`
`443, Reg. Opp. at 7-9). Regeneron cannot rewrite its claims. Regeneron chose not to use
`
`“consisting of” language. It cannot now interpret claim 18 as if it did. Aventis Pharma
`
`Deutschland GmbH v. Lupin Ltd., No. CIV.A. 2:05CV421, 2006 WL 1314413, at *7-8 (E.D. Va.
`
`May 11, 2006) (refusing to equate “substantially free” to “consisting essentially of” when
`
`considering isomer and other impurities because patentee chose not to use the latter term).
`
`Moreover, “consisting of” denotes precise ingredients or components to include to meet
`
`the invention’s goals. The routine additive in the accused water-alcohol mixture did not frustrate
`
`them in Conoco. 460 F.3d at 1360. Amorphous composites “consisting of” drug and HPC
`
`excipient could not accept a solvent in the role of excipient; but could if just an impurity. Otsuka,
`
`2022 WL 2952759, at *3. But, “does not contain phosphate” is a negative term of exclusion. The
`
`exclusionary purpose is lost when phosphate of any amount or kind, is present.
`
`D.
`
`The component list in the Summary Table is not a “specification” under the
`FDA regulations for purposes of Sunovion.
`
`Regeneron also proposes that it can ignore
`
`
`
`is a specification under Sunovion, 731 F.3d at 1278. (Dkt. 443, Reg. Opp. at 9). The fatal flaw in
`
`this theory is that the Summary Table is not a “specification” under FDA standards. Legally, they
`
`because the Summary Table
`
`7
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`

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`show the inapplicability of Sunovion, FDA never required Mylan or anyone else to affirm the
`
`YESAFILITM BLA product does not contain phosphate, or risk rejection of the application.
`
`Thus, Mylan’s motion for summary judgment for claim 18 should be granted.
`
`III. MYLAN SHOULD RECEIVE SUMMARY JUDGMENT ON THE REMAINING
`DOSING PATENT ISSUES.
`
`A.
`
`Regeneron concedes it will not assert direct infringement by Mylan.
`
`Regeneron will not contend that Mylan directly infringes, but objects that entering
`
`summary judgment is an improper “advisory” opinion. (Dkt. 443, Reg. Opp. at 3, 12). Mylan’s
`
`Counterclaims seek a declaration of no direct infringement. (Dkt. 435 at ¶¶ 120 (“Mylan … will
`
`not directly … infringe… the ‘601 patent”); 184 (same, for ‘572 patent)). Summary judgment is
`
`appropriate because it resolves live counterclaims.
`
`B.
`
`The ‘601 patent.
`
`Aside from the direct infringement issue above, Regeneron’s invalidity stipulations resolve
`
`Mylan’s summary judgment motion as to the ‘601 patent, leaving for trial just the issue of induced
`
`infringement and invalidity of claims 11, 19, and 27.
`
`C.
`
`Regeneron must be clear that it will not dispute for trial that the “visual
`acuity” elements in claims 1 and 16 of the ‘572 patent lack patentable weight.
`
`Regeneron’s visual acuity arguments wrongly accuse Mylan of construing the claims one
`
`way for induced infringement, and another for invalidity, contrary to the Court’s claim
`
`construction order. (Dkt. 443, Reg. Opp. at 10, 12-15). That is both incorrect, and not even the
`
`issue. Claims 1 and 16 of the ‘572 patent do not use the specific “Best Corrected Visual Acuity”
`
`claim language the Court construed. They state, “wherein the patient achieves a gain in visual
`
`acuity within 52 weeks following the initial dose.” (Dkt. 443-1, Reg. SMF Resp. ¶ 30; see also
`
`id. at ¶ 34). Regeneron does not dispute that asserted claims 6-7, 12-13, 18-19, and 22-23 of the
`
`‘572 patent contain this 52-week “visual acuity” language, “by virtue of dependency” on claims 1
`
`9
`
`

`

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`and/or 16. (See id. at ¶ 34). Regeneron, not Mylan, has been unclear about treating these terms
`
`identically or differently. Regeneron’s experts applied the 52-week visual acuity term of claims 1
`
`and 16, and BCVA, interchangeably. Yet, before the PTAB, Regeneron argued the “visual acuity”
`
`language in claim 1 was an independent efficacy requirement. (Ex. 37, IPR2022-01524, Paper 7
`
`at 18-19). In its brief, Regeneron proclaims that there is a “mountain of evidence” that Mylan
`
`encourages “the visual acuity measurements recited in the asserted claims.” (Dkt. 443, Reg. Opp.
`
`at 12-13). But, Regeneron argues “under the Court’s construction, Regeneron need not prove that
`
`the visual acuity language is performed ….” (Id. at 15). It is Regeneron, not Mylan, seeking to
`
`apply a “heads we win, tails you lose” approach. (Id. at 10).
`
`1.
`
`Regeneron must clearly confirm the 52-week visual acuity language of
`claims 1 and 16 lacks patentable weight via the Court’s construction.
`
`Mylan limited Section VI of its opening brief to the ‘572 patent precisely to target the
`
`language, “wherein the patient achieves a gain in visual acuity within 52 weeks following the
`
`initial dose.” (Dkt. 432-1 at 6, 7, 9-14). So long as everyone agrees that when Regeneron says the
`
`“visual acuity language” is non-limiting (Dkt. 443, Reg. Opp. at 15), this includes the clauses in
`
`claims 1 and 16 of the ‘572 patent which read, “wherein the patient achieves a gain in visual acuity
`
`within 52 weeks following the initial dose,” then Mylan agrees that this Court need not go further
`
`on divided infringement or inducement for the ‘572 patent on summary judgment.
`
`2.
`
`If the 52-week visual acuity language of claims 1 and 16 has patentable
`weight, then Regeneron cannot meet its burden of proof.
`
`a.
`
`Regeneron fails in its burden on divided infringement.
`
`Mylan established that Regeneron failed to meet its burden of proof regarding infringement
`
`of the 52-week visual acuity language in claims 1 and 16 of the ‘572 patent. (Dkt. 432-1 at 2, 6-
`
`16). In response, Regeneron complains Mylan lacks expert testimony on the issue (Dkt. 443, Reg.
`
`Opp. at 16), an argument that improperly tries to shift its burden onto Mylan. Regeneron’s string
`
`10
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`

`

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`cites that a doctor measures visual acuity (Dkt. 443, Reg. Opp. at 17) are irrelevant. What doctors
`
`must “direct or control” is the claimed patient activity—achieving visual acuity gains within 52
`
`weeks. (See id.). Doctors cannot direct, control, or predict this. (Dkt. 443-1, Reg. SMF Resp. ¶
`
`61). Regeneron had its opportunity to provide evidence that they do, but offers none. Summary
`
`judgment on divided infringement is proper.
`
`b.
`
`Regeneron fails in its burden on induced infringement.
`
`The heart of Regeneron’s inducement theory is that once the YESAFILITM label stated it
`
`was interchangeable with Eylea®, Mylan then induced every doctor’s aflibercept use—whether
`
`on-label or off-label; patented or unpatented; effective or ineffective; esoteric or routine. (Dkt.
`
`443, Reg. Opp. at 17-22). That is not how inducement under 35 U.S.C. § 271(b) legally works.
`
`“[M]ere knowledge alone of possible infringement by others is insufficient to prove
`
`inducement.” Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1364 (Fed. Cir. 2003).
`
`Inducement requires that Mylan “knowingly aided and abetted another’s direct infringement.” Id.
`
`at 1363. When “a product has substantial noninfringing uses, intent to induce infringement cannot
`
`be inferred even when the defendant has actual knowledge that some users of its product may be
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`infringing the patent.” Id. at 1365. Inducing instructions also must specifically instruct another
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`party to perform “every single step in the method” that the patent claims require. Ericsson, Inc. v.
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`D-Link Sys., Inc., 773 F.3d 1201, 1219 (Fed. Cir. 2014). If the instructions include some, but not
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`all, method steps claimed, or is indifferent as to which choice a user makes, the label is not
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`inducing. See Shire LLC v. Amneal Pharms., LLC, No. CIV.A. 11-3781 SRC, 2014 WL 2861430,
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`at *5 (D.N.J. June 23, 2014) (“the statement that the medication may be taken with or without food
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`cannot be reasonably understood to be an instruction to engage in an infringing use”; it is
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`“indifferent to which option is selected”).
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`A drug label cannot encourage, recommend, or promote infringement when the acts at
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`Case 1:22-cv-00061-TSK-JPM Document 466 *SEALED* Filed 05/15/23 Page 21 of 25 Case 1:22-cv-00061-TSK-JPM Document 628 Filed 09/01/23 Page 21 of 274 PageID #:
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`PageID #: 3550549431
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`issue, if performed, do not obligate a doctor or patient to actually perform each and every required
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`step of the claims. HZNP Medicines LLC v. Actavis Laboratories UT, Inc., 940 F.3d 680 (Fed.
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`Cir. 2019) confirmed this. The patented method in HZNP required three distinct steps: (1) applying
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`diclofenac, (2) waiting for the treated area to dry and (3) applying, e.g., sunscreen. Id. at 702. The
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`label instructions “only require the first step of this method, nothing else,” and while the label
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`instructions stated, “[w]ait until area is completely dry before covering with clothing or applying
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`sunscreen, insect repellent, cosmetics, … or other substances,” id. at 700, that step was optional,
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`not mandatory. Id. at 702. A label “does not encourage infringement, particularly where the label
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`does not require” using each claimed method step. Id.
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`Regeneron argues it marshalled a “complete arsenal” of undisputed evidence that doctors
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`regularly assess their patients, (Dkt. 443, Reg. Opp. at 17, 19); that the YESAFILITM label instructs
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`“administer[ing] [] YESAFILITM to patients,” (id. at 18); that YESAFILITM is “highly similar” to
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`Eylea® (Dkt. 443-1, Reg. SMF Resp. ¶ 40); that doctors using YESAFILITM will reach similar
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`results as with Eylea®; that YESAFILITM is interchangeable with Eylea®; and that assessing for
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`visual acuity is a routine, common, and desirable physician practice. (Dkt. 443, Reg. Opp. at 18-
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`21; Dkt. 443-1, Reg. SMF Resp. ¶¶ 39-47). Regeneron insists that “physicians overwhelmingly
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`understand” that they should measure visual acuity when they are treating patients with anti-VEGF
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`agents. (Dkt. 443, Reg. Opp. at 19). Even if true, it is irrelevant. The claimed method step is to
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`achieve visual acuity gains in patients. Regeneron argues it “does not matter” that YESAFILITM’s
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`label instructions do not mention visual acuity gains specifically. (Id. at 19, n.8). But that is the
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`only relevant fact that matters—if claims 1 and 16 require patients to achieve a gain in visual
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`acuity, the label must instruct this step to induce. A label that lacks an instruction to the specific
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`element in the method cannot induce. Warner-Lambert, 316 F.3d at 1364-65 (no inducement of
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`12
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`Case 1:22-cv-00061-TSK-JPM Document 466 *SEALED* Filed 05/15/23 Page 22 of 25 Case 1:22-cv-00061-TSK-JPM Document 628 Filed 09/01/23 Page 22 of 274 PageID #:
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`PageID #: 3550649432
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`off-label uses even assuming doctors used the drug for that purpose).
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`Regeneron complains that “Mylan’s Motion asks the Court to credit attorney argument
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`over the sworn testimony of both sides’ experts.” (Dkt. 443, Reg. Opp. at 19). No. Mylan’s
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`Motion asks the Court to look for legally relevant evidence—instructions to perform each and
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`every step in the claimed method. Regeneron lacks a crucial instruction in the YESAFILITM
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`labeling: an instruction that patients achieve the claimed visual acuity gains.
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`Regeneron also complains it is not “credible” for Mylan to state it does not intend for
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`doctors to assess visual acuity, which it calls a “callous disregard for patient care.” (Dkt. 443, Reg.
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`Opp. at 19-20). This is irrelevant hyperbole. “The pertinent question is whether the proposed
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`label instructs users to perform the patented method.” AstraZeneca LP v. Apotex, Inc., 633 F.3d
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`1042, 1060 (Fed. Cir. 2010). Moreover, Mylan has sold its BLA to another company. (Ex. 40, 11-
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`29-22 Viatris Form 8-K at Ex. 99.1) (announcing transaction transferring biosimilar assets to
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`Biocon);
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`
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`Regeneron has yet to explain how Mylan intends to aid and abet infringement via this third party.
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`Regeneron’s final set of specific-letter arguments fare no better.4 Regeneron argues,
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`without citation, that the YESAFILITM label “expressly instructs” administering it “for patented
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`indications.” (Dkt. 443, Reg. Opp. at 21). Regeneron does not offer a label statement that
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`specifies, “go measure” the claimed letter standards; but rather only that doctors “understand” that
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`administering aflibercept may include “measurement of visual acuity gains.” (Id. at 22). Again,
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`whatever doctors do or don’t understand, or are motivated to measure, label inducement requires
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`4 Regeneron mischaracterizes GlaxoSmithKline LLC v. Teva Pharms. USA, Inc., 7 F.4th 1320,
`1326 (Fed. Cir. 2021). (Dkt. 443, Reg. Opp. at 21). Teva had a small molecule ANDA, so the
`therapeutic equivalence regulatory standard is “bioequivalence”; for biological molecules, it is
`“interchangeable.” 21 C.F.R. § 320.33; 42 U.S.C. §§ 262(i)(3), (k). The scientific conferences are
`also not the label; and are irrelevant now that Mylan sold its BLA to a third party.
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`13
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`PageID #: 3550749433
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`the label must instruct to administer aflibercept and measure and achieve the results that the
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`method steps require. Absent label instructions for all claim elements, inducement liability cannot
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`attach as a matter of law. Ericsson, 773 F.3d at 1219.
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`D.
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`Claim elements to DME, or “isotonic solution” and “nonionic surfactant”
`formulation, cannot salvage the claims’ validity.
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`Regeneron now stipulates to the invalidity of claims to, e.g., treating an angiogenic eye
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`disorder by intravitreally dosing aflibercept 2 mg doses via three (3) loading doses, followed
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`thereafter by every 8-week dosing. (Dkt. 433, Reg. Opp. at 1 (conceding, e.g., invalidity of claims
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`5-6 and 9 of the ‘601 patent; and claims 1-5 of the ‘572 patent)). The prior art Dixon publication,
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`among others, expressly disclosed these steps. (Dkt. 432-1 at Section VII).
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`Regeneron argues that claims 18, 19, 22, and 23 are different for being “directed to treating
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`diabetic macular edema” (“DME”). (Dkt. 443, Reg. Opp. at 24). That is not a patentable
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`distinction in the wake of Regeneron’s invalidity stipulation for claim 1 of the ‘572 patent (Dkt.
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`433., Reg. Opp. at 1). Claim 1 covered a “method of treating an angiogenic eye disorder” using
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`the dosing regimen. (Dkt. 432-21, ‘572 patent at col. 23 ll. 2-14). The ‘572 patent’s specification
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`admits that DME is an angiogenic eye disorder. (Id. at Abstract; col. 1, ll. 40-47; col. 5, ll. 35-42).
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`Dixon expressly stated that aflibercept, i.e., “VEGF Trap-Eye,” was already in clinical trial use
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`“for the treatment of diabetic macular edema (DME).” (Dkt. 432-29, Dixon at MYL-
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`AFL0005012).
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`Regeneron also argues that elements in claims 6-7, 12-13, 18-19, 22, and 23 involving
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`aflibercept formulated “as an isotonic solution” (claims 6, 12, 18, 22); or “with a nonionic
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`surfactant” (claims 7, 13, 19