Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 1 of 31 PageID #: 47825
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF WEST VIRGINIA
`AT CLARKSBURG
`
`
`Plaintiff,
`
`
`v.
`
`
`REGENERON PHARMACEUTICALS, INC.,
`
`
`
`
`MYLAN PHARMACEUTICALS INC.,
`
`
`
`
`
`
`Case No. 1:22-cv-00061-TSK
`
`
`OUTSIDE COUNSEL EYES ONLY
`
`FILED UNDER SEAL
`
`
`
`Defendant.
`
`
`
`
`
`DEFENDANT MYLAN PHARMACEUTICALS INC.’S L.R. CIV. P. 7.02 STATEMENT
`OF UNCONTROVERTED FACTS FOR PURPOSES OF MYLAN’S MOTION FOR
`SUMMARY JUDGMENT OR PARTIAL SUMMARY JUDGMENT ON U.S. PATENT
`NOS. 11,104,715 (PROCESS PATENT); 11,084,865 (FORMULATION PATENT); AND
`10,888,601 & 11,253,572 (DOSING PATENTS)
`
`
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 2 of 31 PageID #: 47826
`
`TABLE OF CONTENTS
`
`TABLE OF ABBREVIATIONS ................................................................................................... iii
`
`TABLE OF RECORD CITATIONS ............................................................................................. iv
`
`I.
`
`The Asserted Patents and Claims, and Relevant Regeneron Statements. ........................... 1
`
`A.
`
`The ‘715 manufacturing patent. .............................................................................. 1
`
`1.
`
`2.
`
`The ‘715 patent and claims. ........................................................................ 1
`
`Regeneron has not contested that Mylan’s accused process does
`not infringe the ‘715 patent’s independent claims under Mylan’s
`claim construction, which the Court has now adopted (Dkt. 427,
`Markman Order at 53-54, 75). .................................................................... 2
`
`B.
`
`The ‘865 formulation patent. .................................................................................. 4
`
`1.
`
`2.
`
`The ‘865 patent and claims. ........................................................................ 4
`
`The YESFALI accused product and phosphate content. ............................ 4
`
`C.
`
`The ‘572 and ‘601 dosing patents. .......................................................................... 5
`
`1.
`
`2.
`
`3.
`
`‘572 patent asserted claims. ........................................................................ 6
`
`‘601 patent asserted claims. ........................................................................ 9
`
`Regeneron’s theories of infringement. ...................................................... 12
`
`a.
`
`b.
`
`No evidence of direct infringement by Mylan. ............................. 12
`
`Regeneron’s experts have not performed an element-by-
`element comparison of the Eylea® labeling to the claims............. 12
`
`c.
`
`Statements relating to the issue of inducement. ............................ 13
`
`i.
`
`ii.
`
`iii.
`
`Labeling statements. ......................................................... 13
`
`Performance statements. ................................................... 15
`
`Regeneron expert statements about performing various
`dosing regimens with 2 mg aflibercept. ............................ 16
`
`iv.
`
`Presentations. .................................................................... 17
`
`4.
`
`Anticipation............................................................................................... 18
`
`i
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 3 of 31 PageID #: 47827
`
`a.
`
`b.
`
`Dixon’s disclosures. ...................................................................... 18
`
`Regeneron’s statements regarding anticipation. ........................... 19
`
`i.
`
`ii.
`
`Visual Acuity. ................................................................... 20
`
`Exclusion criteria. ............................................................. 23
`
`
`
`
`
`
`ii
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 4 of 31 PageID #: 47828
`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 4 of 31 PagelD #: 47828
`
`Abbreviation
`“865 patent or the
`Formulation Patent
`‘601 patent
`
`601 Contentions
`
`TABLE OF ABBREVIATIONS
`
`a
`
`U.S. Patent No. 11,084,865
`U.S. Patent No. 10,888,601
`
`Final Infringement Contentions of Plaintiff Regeneron Pharmaceuticals,
`Inc. for U.S. Patent No. 10,888.601
`
`‘572 Contentions
`
`Final Infringement Contentions of Plaintiff Regeneron Pharmaceuticals,
`Inc. for U.S. Patent No. 11,253,572
`Apotex Inc. v. Regeneron Pharms., Inc., IPR2022-01524, Paper 9
`P.T.A.B. Mar. 10, 2023
`
`‘572 patent
`
`‘572 Institution
`Decision
`“715 patent or the
`Manufacturing Patent
`
`715 Contentions
`Albini Opn.
`2, 2023 Opening Expert Report of Dr. Thomas A. Albini
`Feb
`BCVA
`Best Corrected Visual Acui
`
`CDM Chemically Defined Media or Chemically Defined Medium
`James A Dixonet al., VEGF Trap-Eyefor the Treatment ofNeovascular
`Age-Related Macular Degeneration, 18 EXPERT OPINION ON
`
`USS. Patent No. 11,104,715
`Inc. for U.S. Patent No. 11,104,715
`Final Infringement Contentions of Plaintiff Regeneron Pharmaceuticals,
`INVESTIGATIONAL Drucs 1573 (2009
`
`Retinopathy Study Letter Score
`
`
`
`March 30, 2023 Supplemental Responsive Expert Report of Gregory
`MacMichael, Ph.D. Regarding the Non-Infringement of Claim 18 of U.S.
`Patent No. 11,084,865
`
`
`
`Dixon
`
`Dosing Patents
`
`ee
`
`Csaky
`
`Csaky
`Csaky
`
`Opn.
`
`Resp.
`Repl
`
`Csaky
`Tr.
`ChuTr.
`
`MacMichael Supp.
`
`Manning Rep.
`
`POSA
`
`PTAB
`
`Retina Society, VEGF Trap-Eye in Wet AMD CLEAR-IT 2: Summary of
`Retina Society Meeting|One-Year Key Results, A Phase 2, Randomized, Controlled Dose- and
`Presentation 2008
`Interval-Ranging Study ofIntravitreal VEGF Trap-Eye in Patients With
`Neovascular, Age-Related Macular Degeneration(Sept. 28, 2008
`February 2, 2023 Opening Expert Report and Declaration of Dr. Franklin
`Swartzwelder Regarding Mylan’s Infringement of U.S. Patent No.
`11,104,715
`2
`,
`
`Swartzwelder Opn.
`
`Trout Opn.
`
`
`
`
`ing Expert Report of Bernhardt L. Trout, Ph.D.
`
`ill
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 5 of 31 PageID #: 47829
`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 5 of 31 PagelD #: 47829
`
`
`
`Trout Repl
`SwartzwelderTr.
`
`March 30, 2023 Reply Expert Report of Bernhardt L. Trout, Ph.D.
`Transcript of April 12, 2023 Deposition of Franklin Swartzwelder
`Transcript of January
`18, 2023 Deposition of George D. Yancopoulos
`YESAFILI™,the accused product, which is the aflibercept-containing
`T™
`productthat is the subject ofBiologics License Application No.
`
`Proposed Prescribing Information for YESAFILI™,last revised August
`2022
`
`YESAFILI
`
`YESAFILI™label
`Abbreviation Dkt. 427, Markm:
`
`TABLE OF RECORD CITATIONS
`
`Order eens
`
`Order on Claim Construction, dated April 19, 2023
`
`}
`
`iv
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 6 of 31 PageID #: 47830
`
`Mylan Pharmaceuticals Inc. (“Mylan”) has moved for summary judgment for multiple
`
`patents that Plaintiff Regeneron Pharmaceuticals, Inc. (“Regeneron”) asserts. Following is
`
`Mylan’s Local Rule of Civil Procedure 7.02 Statement of Uncontroverted Facts.
`
`I.
`
`The Asserted Patents and Claims, and Relevant Regeneron Statements.
`
`A.
`
`The ‘715 manufacturing patent.
`
`1.
`
`The ‘715 patent and claims.
`
`1.
`
`Regeneron accused the process used by Mylan to culture aflibercept, designated
`
`M710, of infringing process claims 2-3, 6, 12-14, and 16 of the ‘715 patent. (Ex. 1, Swartzwelder
`
`Opn. ¶ 2).
`
`2.
`
`Each of claims 2-3, 6, and 12-14 of the ‘715 patent depend upon independent claim
`
`1 of the ‘715 patent. (Ex. 11, ‘715 patent, claims 2-3, 6, 12-14 (claims referencing “The method
`
`of claim 1;” “The method of claim 2,” which in turn references “The method of claim 1;” or “The
`
`method of claim 13,” which in turn references “The method of claim 1”); Ex. 1, Swartzwelder
`
`Opn. ¶¶ 136-38, 147, 152-54, 157).
`
`3.
`
`Claim 1 of the ‘715 patent recites:
`
`A method of producing aflibercept harvested from a host cell cultured in a chemically
`defined medium (CDM), comprising:
`(a) providing a host cell genetically engineered to express aflibercept;
`(b) culturing said host cell in said CDM under conditions suitable in which said host cell
`expresses said aflibercept wherein the cumulative concentration of nickel in said CDM is
`less than or equal to 0.4 μM or about 0.4 μM
`and one or more of the following:
`i. the cumulative concentration of iron in said CDM is less than or equal to 55.0 μM;
`ii. the cumulative concentration of copper in said CDM is less than or equal to 0.8 μM;
`iii. the cumulative concentration of zinc in said CDM is less than or equal to 56.0 μM;
`iv. the cumulative concentration of cysteine in said CDM is less than or equal to 10.0
`mM, and
`v. said CDM includes anti-oxidants where the cumulative concentration of an antioxidant
`is about 0.001 mM to about 10.0 mM for any single anti-oxidant; and
`(c) harvesting aflibercept produced by said host cell.
`
`(Ex. 11, 715 patent at claim 1; Ex. 1, Swartzwelder Opn. ¶ 63).
`
`1
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 7 of 31 PageID #: 47831
`
`4.
`
`Claim 16 is also an independent claim in the ‘715 patent. It recites:
`
`A method of producing aflibercept harvested from a host cell cultured in a chemically
`defined medium (CDM), comprising:
`(a) culturing said host cell in said CDM under conditions suitable in which said host cell
`expresses said aflibercept wherein the cumulative concentration of nickel in said CDM is
`less than or equal to 0.4 μM or about 0.4 μM and one or more of the following:
` i. the cumulative concentration of iron in said CDM is less than or equal to 55.0 μM;
` ii. the cumulative concentration of copper in said CDM is less than or equal to 0.8 μM;
` iii. the cumulative concentration of zinc in said CDM is less than or equal to 56.0 μM;
` iv. the cumulative concentration of cysteine in said CDM is less than or equal to 10.0 mM,
`and
`v. said CDM includes anti-oxidants where the cumulative concentration of an antioxidant
`is about 0.001 mM to about 10.0 mM for any single anti-oxidant; and
`(b) harvesting aflibercept produced by said host cell.
`
`
`
`(Ex. 11, 715 patent at claim 16; Ex. 1, Swartzwelder Opn. ¶ 70).
`
`2.
`
`Regeneron has not contested that Mylan’s accused process does not
`infringe the ‘715 patent’s independent claims under Mylan’s claim
`construction, which the Court has now adopted (Dkt. 427, Markman
`Order at 53-54, 75).
`
`5.
`
`Regeneron’s expert Dr. Swartzwelder, offering his opinions in this case, stated that
`
`he “applied Regeneron’s proposed construction of ‘cell(s) cultured in a chemically defined
`
`medium,’” and that he “ha[s] not analyzed whether Mylan’s process is covered by claim 1 were
`
`Mylan’s construction of ‘cell(s) cultured in a chemically defined medium’ to be applied.” (Ex. 1,
`
`Swartzwelder Opn. ¶ 74; id. ¶ 73; id. ¶ 113 (for the term “host cell cultured in a chemically defined
`
`medium (CDM),” Swartzwelder “ha[s] applied Regeneron’s construction” for independent claims
`
`1 and 16 to exclude situations “where the cell is subsequently cultured in a nonchemically defined
`
`medium.”)).
`
`6.
`
`Regeneron’s expert, Dr. Swartzwelder, opined that:
`
`2
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 8 of 31 PageID #: 47832
`
`(Ex. 1, Swartzwelder Opn. ¶ 81).
`
`7.
`
`Regeneron’s expert, Dr. Swartzwelder, has assumed for purposes of his
`
`infringement opinions that “methods are not excluded” from the scope of the claim term “host cell
`
`cultured in a chemically defined medium (CDM)” when “the cell is subsequently cultured in a
`
`non-chemically defined medium.” (Ex. 1, Swartzwelder Opn. ¶ 113).
`
`8.
`
`Regeneron’s expert, Dr. Swartzwelder, opined that:
`
`(Ex. 1, Swartzwelder Opn. ¶ 93).
`
`9.
`
`Regeneron’s expert, Dr. Swartzwelder, opined that:
`
`(Ex. 1, Swartzwelder Opn. ¶ 94).
`
`10.
`
`Regeneron’s expert, Dr. Swartzwelder, opined that:
`
`(Ex. 1, Swartzwelder Opn. ¶ 94).
`
`11.
`
`Regeneron’s expert, Dr. Swartzwelder, opined that:
`
`(Ex. 1, Swartzwelder Opn. ¶ 102).
`
`12.
`
`Regeneron’s expert, Dr. Swartzwelder, has not opined that Mylan infringes under
`
`Mylan’s claim construction. (¶¶ 5-11 above).
`
`13.
`
`Regeneron’s expert, Dr. Swartzwelder, provided the following testimony at his
`
`deposition:
`
`3
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 9 of 31 PageID #: 47833
`
`
`
`
`(Ex. 2, Swartzwelder Tr. at 133:6-12).
`
`14.
`
`Regeneron’s infringement contentions did not assert that Mylan infringes under
`
`Mylan’s claim construction. (Ex. 12, ‘715 Contentions at 4-10).
`
`B.
`
`The ‘865 formulation patent.
`
`1.
`
`The ‘865 patent and claims.
`
`15.
`
`The ‘865 patent states that it is directed towards, among other things, “liquid
`
`pharmaceutical formulations having increased stability.” (Ex. 13, ‘865 patent at 1:49-50).
`
`16.
`
`Regeneron asserts that the proposed M710 aflibercept product “infringes at least
`
`claims 4, 7, 9, 11 and 14-18 of the [‘]865 patent.” (Ex. 14, Trout Opn., Section X).
`
`17.
`
`Claim 18 of the ‘865 patent reads as follows: “The vial of claim 5, wherein said
`
`formulation does not contain phosphate.” (Ex. 13, ‘865 patent at claim 18).
`
`2.
`
`The YESFALI accused product and phosphate content.
`
`18.
`
`Regeneron’s expert Dr. Trout offered the following limited opinions regarding
`
`whether Mylan’s aflibercept product (which Dr. Trout refers to as the accused “M710” product in
`
`his report) “does not contain phosphate” for claim 18:
`
`
`
` Accordingly, M710 does not contain phosphate
`and thus falls within the limitation of claim 18…
`
`(Ex. 14, Trout Opn. ¶ 142).
`
`19.
`
`Regeneron’s expert Dr. Trout’s Section X.A.5 is titled “M710 comprises a buffer,”
`
`and states as follows regarding the M710 product:
`
`4
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 10 of 31 PageID #:
`47834
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 11 of 31 PageID #:
`47835
`
`1 [of the Dosing Patents] was referred to as the CLEAR-IT 1 study.” (Ex. 10, Chu Tr. at 169:5-
`
`17).
`
`26.
`
`Regeneron’s 30(b)(6) witness, Ms. Karen Chu, testified that “[t]he study in example
`
`2 was the CLEAR-IT 2 study.” (Ex. 10, Chu Tr. at 169:15-17).
`
`27.
`
`Regeneron’s 30(b)(6) witness, Ms. Karen Chu, testified that “example 4 refers to
`
`two parallel Phase III clinical trials carried out to investigate the use of VEGF-T to treat patients
`
`with the neovascular form of age-related macular degeneration, so this section appears to be
`
`referring to both the VIEW 1 and the VIEW 2 studies.” (Ex. 10, Chu Tr. at 169:23 – 170:5).
`
`28.
`
`Regeneron’s expert, Dr. Csaky, agrees that Example 4 in the ‘601 and ‘572 patents
`
`lists thirty-seven (37) exclusion criteria, including ocular inflammation and active ocular or
`
`periocular infection. (Ex. 4, Csaky Resp. ¶ 388).
`
`1.
`
`‘572 patent asserted claims.
`
`29.
`
`Regeneron is currently asserting claims 1-14, 16-23, and 25-28 of the ‘572 patent
`
`against Mylan. (Ex. 19, Csaky Reply ¶ 3).
`
`30.
`
`The ‘572 patent asserted claims are below in bold, along with the unasserted claims
`
`from which they depend:
`
`1. A method of treating an angiogenic eye disorder in a patient
`in need thereof comprising sequentially administering to the
`patient by intravitreal injection a single initial dose of 2 mg of
`aflibercept, followed by one or more secondary doses of 2 mg of
`aflibercept, followed by one or more tertiary doses of 2 mg of
`aflibercept; wherein each secondary dose is administered
`approximately 4 weeks following the immediately preceding
`dose; and wherein each tertiary dose
`is administered
`approximately 8 weeks following the immediately preceding
`dose; wherein the patient achieves a gain in visual acuity within
`52 weeks following the initial dose.
`
`2. The method of claim 1 wherein the patient achieves a gain in
`Best Corrected Visual Acuity (BCVA) according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score.
`
`6
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 12 of 31 PageID #:
`47836
`
`3. The method of claim 2 wherein the patient gains at least 7
`letters Best Corrected Visual Acuity (BCVA) according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score.
`
`4. The method of claim 3 wherein the patient achieves the gain
`in visual acuity within 24 weeks following the initial dose.
`
`5. The method of claim 3 wherein only two secondary doses are
`administered to the patient.
`
`6. The method of claim 3 wherein the aflibercept is formulated
`as an isotonic solution.
`
`7. The method of claim 3 wherein the aflibercept is formulated
`with a nonionic surfactant.
`
`8. The method of claim 2 wherein the patient gains at least 8
`letters Best Corrected Visual Acuity (BCVA) according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score.
`
`9. The method of claim 8 wherein the patient achieves the gain
`in visual acuity within 24 weeks following the initial dose.
`
`10. The method of claim 2 wherein the patient gains at least 9
`letters Best Corrected Visual Acuity (BCVA) according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score.
`
`11. The method of claim 10 wherein only two secondary doses
`are administered to the patient.
`
`12. The method of claim 10 wherein the aflibercept is
`formulated as an isotonic solution.
`
`13. The method of claim 10 wherein the aflibercept is
`formulated with a nonionic surfactant.
`
`14. The method of claim 1 wherein exclusion criteria for the
`patient include both of: (1) active ocular inflammation; and (2)
`active ocular or periocular infection.
`
`15. A method of treating diabetic macular edema in a patient in need
`thereof comprising sequentially administering to the patient a single
`initial dose of 2 mg of aflibercept, followed by one or more
`secondary doses of 2 mg of aflibercept, followed by one or more
`tertiary doses of 2 mg of aflibercept; wherein each secondary dose
`is administered to the patient by intravitreal injection approximately
`4 weeks following the immediately preceding dose; and wherein
`each tertiary dose is administered to the patient by intravitreal
`
`7
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 13 of 31 PageID #:
`47837
`
`injection approximately 8 weeks following the immediately
`preceding dose.
`
`16. The method of claim 15 wherein the patient achieves a gain
`in visual acuity within 52 weeks following the initial dose.
`
`17. The method of claim 16 wherein the patient gains at least 9
`letters Best Corrected Visual Acuity (BCVA) according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score.
`
`18. The method of claim 17 wherein the aflibercept is
`formulated as an isotonic solution.
`
`19. The method of claim 17 wherein the aflibercept is
`formulated with a non-ionic surfactant.
`
`20. The method of claim 17 wherein the patient achieves a gain
`in visual acuity within 24 weeks following the initial dose.
`
`21. The method of claim 16 wherein the patient gains at least 8
`letters Best Corrected Visual Acuity (BCVA) according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score.
`
`22. The method of claim 21 wherein the aflibercept is
`formulated as an isotonic solution.
`
`23. The method of claim 21 wherein the aflibercept is
`formulated with a nonionic surfactant.
`
`25. The method of claim 15 wherein four secondary doses are
`administered to the patient.
`
`26. A method of treating age related macular degeneration in a
`patient in need thereof comprising sequentially administering to
`the patient a single initial dose of 2 mg of aflibercept, followed
`by one or more secondary doses of 2 mg of aflibercept, followed
`by one or more tertiary doses of 2 mg of aflibercept; wherein
`each secondary dose is administered to the patient by
`intravitreal injection approximately 4 weeks following the
`immediately preceding dose; and wherein each tertiary dose is
`administered
`to
`the patient by
`intravitreal
`injection
`approximately 8 weeks following the immediately preceding
`dose; wherein the method is as effective in achieving a gain in
`visual acuity as monthly administration of 0.5 mg of
`ranibizumab by intravitreal injection in human subjects with
`age-related macular degeneration at 52 weeks following the
`initial dose.
`
`8
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 14 of 31 PageID #:
`47838
`
`27. The method of claim 26 wherein only two secondary doses
`are administered to the patient.
`
`28. The method of claim 26 wherein the gain in visual acuity is
`measured using the Early Treatment Diabetic Retinopathy
`Study (ETDRS) letter score.
`
`(Ex. 18, ‘572 patent at claims; Ex. 3, Csaky Opn. ¶ 67).
`
`2.
`
`‘601 patent asserted claims.
`
`31.
`
`Regeneron is currently asserting claims 5-6, 9, 11-12, 15-17, 19, 21, 23-25, 27-28,
`
`and 31-33 of the ‘601 patent against Mylan. (Ex. 19, Csaky Reply ¶ 3).
`
`32.
`
`The ‘601 patent asserted claims are below in bold, along with the unasserted claims
`
`from which they depend:
`
`1. A method for treating age related macular degeneration in a
`patient in need thereof, comprising intravitreally administering, to
`said patient, an effective amount of aflibercept which is 2 mg
`approximately every 4 weeks for the first 3 months, followed by 2
`mg approximately once every 8 weeks or once every 2 months.
`
`2. The method of claim 1, wherein the age-related macular
`degeneration is neovascular (wet).
`
`5. The method of claim 2 wherein the patient gains at least 15
`letters of Best Corrected Visual Acuity (BCVA) score.
`
`6. The method of claim 5 wherein Best Corrected Visual Acuity
`(BCVA) is according to Early Treatment Diabetic Retinopathy
`Study (ETDRS) letter score.
`
`7. The method of claim 1, wherein approximately every 4 weeks
`comprises approximately every 28 days or approximately monthly.
`
`8. The method of claim 7, wherein the age-related macular
`degeneration is neovascular (wet).
`
`9. The method of claim 8 wherein exclusion criteria for the
`patient include (1) active intraocular inflammation; or (2) active
`ocular or periocular infection.
`
`10. A method for treating diabetic macular edema in a patient in
`need thereof, comprising intravitreally administering, to said
`
`9
`
`

`

`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 15 of 31 PageID #:
`47839
`
`patient, an effective amount of aflibercept which is 2 mg
`approximately every 4 weeks for the first 5 injections followed by 2
`mg approximately once every 8 weeks or once every 2 months.
`
`11. The method of claim 10, wherein approximately every 4
`weeks comprises approximately every 28 days or approximately
`monthly.
`
`12. The method of claim 10, further comprising, after 20 weeks,
`administering, via intravitreal injection, 2 mg of aflibercept
`once every 4 weeks.
`
`15. The method of claim 10 wherein the patient gains at least 15
`letters of Best Corrected Visual Acuity (BCVA) score.
`
`16. The method of claim 15 wherein Best Corrected Visual
`Acuity (BCVA) is according to Early Treatment Diabetic
`Retinopathy Study (ETDRS) letter score.
`
`17. The method of claim 10 wherein exclusion criteria for the
`patient include (1) active intraocular inflammation; or (2) active
`ocular or periocular infection.
`
`18. A method for treating diabetic retinopathy in a patient in need
`thereof, comprising intravitreally administering, to said patient, an
`effective amount of aflibercept which is 2 mg approximately every
`4 weeks for the first 5 injections followed by 2 mg approximately
`once every 8 weeks or 2 months.
`
`19. The method of claim 18, wherein approximately every 4
`weeks comprises approximately every 28 days or approximately
`monthly.
`
`21. The method of claim 18, further comprising, after 20 weeks,
`administering, via intravitreal injection, 2 mg of aflibercept
`once every 4 weeks.
`
`23. The method of claim 18 wherein the patient gains at least 15
`letters of Best Corrected Visual Acuity (BCVA) score.
`
`24. The method of claim 23 wherein Best Corrected Visual
`Acuity (BCVA) is according to Early Treatment Diabetic
`Retinopathy Study (ETDRS) letter score.
`
`25. The method of claim 18 wherein exclusion criteria for the
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`patient include (1) active intraocular inflammation; or (2) active
`ocular or periocular infection.
`
`26. A method for treating diabetic retinopathy in a patient with
`diabetic macular edema, who is in need of such treatment,
`comprising intravitreally administering, to said patient, an effective
`amount of aflibercept which is 2 mg approximately every 4 weeks
`for the first 5 injections followed by 2 mg approximately once every
`8 weeks or 2 months.
`
`27. The method of claim 26, wherein approximately every 4
`weeks comprises approximately every 28 days or approximately
`monthly.
`
`28. The method of claim 26, further comprising, after 20 weeks,
`administering, via intravitreal injection, 2 mg of aflibercept
`once every 4 weeks.
`
`31. The method of claim 26 wherein the patient gains at least 15
`letters of Best Corrected Visual Acuity (BCVA) score.
`
`32. The method of claim 31 wherein Best Corrected Visual
`Acuity (BCVA) is according to Early Treatment Diabetic
`Retinopathy Study (ETDRS) letter score.
`
`33. The method of claim 26 wherein exclusion criteria for the
`patient include (1) active intraocular inflammation; or (2) active
`ocular or periocular infection.
`
`(Ex. 17, ‘601 patent at claims; Ex. 3, Csaky Opn. ¶ 319).
`
`*
`
`*
`
`*
`
`33.
`
`Several asserted claims in the ‘572 and ‘601 patent list “exclusion criteria for the
`
`patient,” namely “active [intra]ocular inflammation” and/or “active ocular or periocular infection.”
`
`(Ex. 18, ‘572 patent at claim 14; Ex. 17, ‘601 patent at claims 9, 17, 25, and 33).
`
`34.
`
`Several asserted claims in the ‘572 patent and the ‘601 patent include language
`
`relating to visual acuity. The ‘572 patent’s independent claim 1, and dependent claim 16, include
`
`the following claim language: “wherein the patient achieves a gain in visual acuity within 52
`
`weeks following the initial dose.” (Ex. 18, ‘572 patent at claims 1 and 16). The ‘572 patent’s
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`independent claim 26 includes the following claim language: “wherein the method is as effective
`
`in achieving a gain in visual acuity as monthly administration of 0.5 mg of ranibizumab by
`
`intravitreal injection in human subjects with age-related macular degeneration at 52 weeks
`
`following the initial dose.” (Id. at claim 26). The ‘572 and ‘601 patents’ dependent claims include
`
`claim language to visual acuity gains within a certain amount of time, letter scores as measured by
`
`BCVA, and/or ETDRS measurements. (See, e.g., Ex. 18, ‘572 patent at claims 2-4, 8-10, 16, 20-
`
`21, 28; Ex. 17, ‘601 patent at claims 5-6, 15-16, 23-24, 31-32; Ex. 3, Csaky Opn. ¶¶ 67, 319).
`
`3.
`
`Regeneron’s theories of infringement.
`
`a.
`
`No evidence of direct infringement by Mylan.
`
`35. Mylan, as a pharmaceutical company, does not prescribe or treat patients with
`
`medication. (See Ex. 19, Csaky Reply ¶¶ 25-26; Ex. 3, Csaky Opn. ¶¶ 63-65; Ex. 20, ‘572
`
`Contentions at 4; Ex. 21, ‘601 Contentions at 4).
`
`36.
`
`Regeneron’s expert Dr. Csaky did not opine that Mylan would directly infringe any
`
`claim of the ‘572 or ‘601 patents. (Ex. 3, Csaky Opn. ¶¶ 8, 54-55; Ex. 19, Csaky Reply ¶¶ 25-26).
`
`b.
`
`Regeneron’s experts have not performed an element-by-element
`comparison of the Eylea® labeling to the claims.
`
`37.
`
`Regeneron’s expert Dr. Csaky has not in his expert report performed an element-
`
`by-element comparison of the Eylea® labeling to each and every claim element in the Dosing
`
`Patent asserted claims. (See generally Ex. 3, Csaky Opn.; Appendix C; Appendix D).
`
`38.
`
`Regeneron’s expert Dr. Manning has not in his expert report performed an element-
`
`by-element comparison of the Eylea® labeling to each and every element in the Dosing Patent
`
`asserted claims. (See generally Ex. 22, Manning Rep.; Attachments B-Y).
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`c.
`
`Statements relating to the issue of inducement.
`
`i.
`
`Labeling statements.
`
`39.
`
`Regeneron’s expert Dr. Csaky has opined that Mylan will encourage direct
`
`infringement through “YESAFILITM’s proposed labeling and other conduct.” (Ex. 3, Csaky Opn.
`
`¶ 8; see also id. ¶¶ 54-55).
`
`40.
`
`Regeneron’s expert Dr. Csaky opines that statements in the YESAFILITM labeling
`
`“will [] instruct physicians that YESAFILITM is a biosimilar ‘interchangeable’ with Eylea®” such
`
`that “it can be expected to produce the same clinical result” as Eylea® “in any given patient.” (Ex.
`
`3, Csaky Opn. ¶¶ 69-70).
`
`41.
`
`Regeneron’s expert Dr. Csaky opines that “ophthalmologists have administered
`
`Eylea®—consistent with Regeneron’s instructions—in a manner that practices the Asserted
`
`Claims [of the Dosing Patents].” (Ex. 3, Csaky Opn. ¶ 77).
`
`42.
`
`Regeneron’s expert Dr. Csaky has not identified any statements in the proposed
`
`“Dosing and Indications” section of YESAFILITM that will induce infringement of claim language
`
`relating to visual acuity or claim language relating to exclusion criteria. (See generally Ex. 3,
`
`Csaky Opn. at Appendix C, Appendix D).
`
`43.
`
`The citations that Regeneron’s expert Dr. Csaky identifies from the labeling
`
`relating to visual acuity of aflibercept as compared to ranibizumab are found in descriptions of
`
`clinical trial reports. (See, e.g., Ex. 3, Csaky Opn. at Appendix C, pp. 31-32 (citing section 14.1
`
`in labeling)).
`
`44.
`
`Regeneron has not identified any label statements that require or encourage a doctor
`
`to test their patients for visual acuity when dosing with aflibercept; or at or for a particular number
`
`of weeks; or until a patient reaches the particular claimed visual acuity outcomes. (See generally
`
`Ex. 3, Csaky Opn., Appendix C, Appendix D).
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`45.
`
`The only citations that Regeneron’s expert Dr. Csaky provides from the labeling
`
`relating to visual acuity (whether for an independent or dependent claim) are found outside the
`
`dosing and indications section of the labeling. (Ex. 3, Csaky Opn. at Appendix C pp. 5-10,12-15,
`
`20-27, 31-34, Appendix D pp. 3-5, 10-13, 17-24).
`
`46.
`
`The only citations that Regeneron’s expert Dr. Csaky provides from the labeling
`
`relating to visual acuity are found in descriptions of clinical trial reports. (See, e.g., Ex. 3, Csaky
`
`Opn. Appendix C pp. 6-9, 12-14, 20-27, 31-34).
`
`47. Mylan’s YESAFILITM label does not require using the drug to target or reach any
`
`particular visual acuity outcome, or require doctors to perform any visual acuity measurements at
`
`any particular point in time. (Ex. 23, YESAFILITM label at 15-26 (YESAFILITM label only reports
`
`visual acuity effects measured in clinical trials)).
`
`48.
`
`Regeneron’s Rule 30(b)(6), Ms. Chu, testified that Eylea®’s dosing instructions do
`
`not instruct doctors to perform visual acuity measurements, or that patients should reach particular
`
`visual acuity outcomes. (Ex. 10, Chu Tr. 115:1 – 118:10).
`
`49.
`
`Regeneron’s expert, Dr. Csaky, opines that the claim language, “wherein exclusion
`
`criteria for the patient include [both of:] (1) active [intra]ocular inflammation; and (2) active ocular
`
`or periocular infection,” found in claim 14 of ‘572 patent and claims 9, 17, 25, and 33 of the ‘601
`
`patent, is induced by “contraindications” statements in the labeling. (Ex. 3, Csaky Opn. pp. 143-
`
`44 ¶ 337, 397, 468, 538 id. at Appendix C pp. 17-18 (characterizing this as something physicians
`
`regularly do; is part of an unspecified treatment protocol); id. at Appendix D pp. 7, 13-14, 19-20,
`
`29-30 (same)).
`
`50.
`
`Regeneron’s expert Dr. Csaky opined
`
`that
`
`the YESAFILITM
`
`label’s
`
`contraindication statements mean that a patient who follows the dosing regimen will be assessed
`
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`Case 1:22-cv-00061-TSK-JPM Document 616 Filed 09/01/23 Page 20 of 31 PageID #:
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`for exclusion criteria. (Ex. 3, Csaky Opn. pp. 143-44 ¶¶ 334-38, 394-400, 466-72, 536-40; id. at
`
`Appendix C pp. 17-18 (characterizing this as something physicians regularly do; is part of an
`
`unspecified treatment protocol); id. at Appendix D pp. 7, 13-14, 19-20, 29-30 (same)).
`
`51.
`
`Regeneron’s Rule 30(b)(6) witness, Ms. Karen Chu, testified that Eylea®’s dosing
`
`instructions do not instruct doctors to impose exclusion criteria. (Ex. 10, Chu Tr. at 120:4 –
`
`121: