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`25618
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF WEST VIRGINIA
`
`IN RE: AFLIBERCEPT PATENT
`LITIGATION
`
`THIS DOCUMENT RELATES TO
`CASE NO. 1:23-CV-89
`
` MDL NO. 1:24-MD-3103-TSK
`
`** SEALED **
`ORDER GRANTING MOTION FOR PRELIMINARY INJUNCTION
`Pending before the Court is Plaintiff Regeneron’s Motion for
`Preliminary Injunction [ECF Nos. 108, 1311]. The motion is fully
`briefed and ripe for decision. For the reasons set forth herein,
`the motion is GRANTED.
`I.PRELIMINARY STATEMENT
`Plaintiff Regeneron Pharmaceuticals, Inc. (“Regeneron”) filed
`this patent infringement action. Therein, at issue in the
`preliminary injunction is one of those patents: U.S. Patent No.
`11,084,865 (the “Product Patent”). The asserted patent claims are
`associated with Regeneron’s product Eylea® and Celltrion’s filing
`of an abbreviated Biologics License Application (“aBLA”) seeking
`to commercially manufacture, use, import, offer to sell, and/or
`sell “CT-P42,” a biosimilar version of Eylea.
`
`1 All docket references are to member case 1:23-CV-89 unless
`otherwise indicated.
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`FACTUAL BACKGROUND
`II.
`1. Regeneron’s Eylea Product
`Regeneron invented and developed Eylea, which the U.S. Food
`and Drug Administration (“FDA”) approved on November 18, 2011.
`The Court has previously addressed the pertinent background and
`development of Eylea. See Regeneron Pharm., Inc. v. Mylan Pharm.
`Inc., --- F. Supp. 3d ---, 2024 WL 382495, at *13-14 (N.D.W. Va.
`Jan. 31, 2024) (“Mylan”) (discussing relevant background of
`Eylea). “Eylea is an ophthalmic drug product invented by Regeneron
`scientists that has been used to treat millions of patients
`suffering from diseases that can cause vision loss or even
`blindness.” Id. at *13. The active ingredient in Eylea is the
`fusion protein now referred to as aflibercept. Aflibercept was
`initially developed as a cancer therapeutic and Regeneron later
`discovered that aflibercept could be used to treat angiogenic eye
`diseases—eye diseases caused by uncontrolled blood vessel growth
`in the retina—through intravitreal injections (injection into the
`vitreous of the eye). Id. at *13-14.
`After more than a decade of development and multiple clinical
`trials, Regeneron achieved an Eylea formulation that improved on
`the leading treatment for one angiogenic disease—wet Age-Related
`Macular Degeneration (“AMD”). Id. at *13 (quoting Trial Tr.
`
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`172:16-24 (Yancopoulos)). The Eylea formulation contains 40 mg/ml
`aflibercept, 10 mM sodium phosphate, 40 mM sodium chloride, 0.03%
`polysorbate 20, and 5% sucrose, pH 6.2. Id. at *14. Following
`its initial FDA approval, Regeneron tested Eylea effectiveness in
`patients with other angiogenic eye disorders, ultimately obtaining
`approval for Eylea’s use to treat those conditions as well. Id.
`Soon, Eylea “became the new gold standard of care” for treating
`such eye disorders. Mylan Trial Tr. at 172:19-20 (ECF No. 108-
`27, Sheridan Ex. 51).
`Following the success of Regeneron’s Eylea vial formulation,
`Regeneron developed and obtained approval in November 2011 for
`Eylea in a pre-filled syringe (“PFS”). See Sheridan Decl. ¶ 48
`(ECF No. 108-21). Then in August 2023, Regeneron received approval
`to sell Eylea HD, an 8 mg formulation that requires less frequent
`injections and provides improved anatomical outcomes in the form
`of drier retinas. Id.; Clark Decl. ¶ 3 (ECF No. 108-34). Eylea
`HD is currently approved to treat wet AMD, Diabetic Macular Edema
`(“DME”), and Diabetic Retinopathy (“DR”). Clark Decl. ¶ 3.
`2. Other Anti-VEGF Treatments
`For the past five years, Eylea has maintained its place as
`the “category leader” in anti-VEGF treatments,
`
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` The second
`most popular anti-VEGF agent, Avastin (bevacizumab),
` Avastin is an
`oncology drug for metastatic colorectal cancer (among other
`cancers), but ophthalmologists sometimes use it off-label (i.e.,
`for diseases for which it does not have FDA approval) to treat
`angiogenic eye disorders. Sheridan Decl. ¶ 55 (ECF No. 108-21).
`The third- and fourth-most popular anti-VEGF agents, Vabysmo
`(faricimab) and Lucentis (ranibizumab), are approved to treat
`angiogenic eye disorders. Id. ¶¶ 57-59. Genentech manufactures
`all three drugs. Id. ¶¶ 55, 57-59.
`Eylea, Avastin, Vabysmo, and Lucentis make up more than
`of anti-VEGF ophthalmic sales. Clark Decl. ¶ 6; Clark Ex. 1 at 3-
`4. Other products on the market—such as Beovu are prescribed less
`frequently. Regeneron Pharms., Inc. v. Mylan Pharms., Inc., C.A.
`No. 1:22-cv-61, ECF No. 571 (Trial Tr.) at 861:6-862:4 (Albini).
`Overall, Eylea has maintained its category leadership due to its
`safety, efficacy, and dosing regimen advantage. Clark Decl. ¶ 7.
`
`3. Aflibercept Biosimilars
`At least nine pharmaceutical companies are developing and
`seeking FDA approval for aflibercept biosimilars, each of which
`contains the same active ingredient as Eylea, also in a 2 mg vial
`
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`and in some cases PFS formulation. Sheridan Decl. ¶ 49. Absent
`injunctive relief, Regeneron expects
`
`4. Celltrion’s aBLA and Proposed Biosimilar Product
`Celltrion is a Korean biopharmaceutical company headquartered
`in Incheon, South Korea and is focused on the development of
`biosimilars to previously licensed “reference products” like
`Regeneron’s Eylea® product. Shin Decl. ¶¶ 2-3 (ECF No. 68-1). On
`June 30, 2023, Celltrion filed aBLA No. 761377 (“Celltrion’s aBLA”)
`with FDA seeking approval under the Biologics Price Competition
`and Innovation Act (“BPCIA”), 42 U.S.C. §§ 262(k)-(l), to market
`and distribute its biosimilar of Eylea, “CT-P42,” throughout the
`United States, including in West Virginia. Shin Decl. ¶¶ 4, 9.
`
`Celltrion’s aBLA specifies
`
`2 CT-P42 is supplied in two presentations: a vial as part of a vial
`kit and a pre-filled syringe. Trout Decl. App. A ¶¶ 1, 10, 109
`(ECF No. 108-4).
`
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` Trout Decl. App. A ¶ 11 (ECF No. 108-4), and is
`
` Id. ¶ 16 (internal quotations
`omitted); Trout Ex. C-2 (ECF No. 108-5). Celltrion’s aBLA also
`specifies the composition of CT-P42.
`
` Trout Decl. App. A ¶¶ 2-3.
`Celltrion’s aBLA also includes a proposed label to be packaged
`along with the marketed CT-P42 product. See Trout Decl. App. A
`¶¶ 12, 111; Trout Ex. C-2. Like the Eylea label, Celltrion’s
`proposed label recommends that doctors use CT-P42 to treat wet
`AMD, Macular Edema Following Retinal Vein Occlusion (“RVO”), DME,
`and DR. Trout Decl. App. A ¶ 12; Trout Ex. C-2.
`In connection with Celltrion’s aBLA request for FDA approval
`to market CT-P42 in the United States,
`
` Celltrion and a U.S. company
`called Celltrion USA, Inc. (“Celltrion USA”) entered into a Master
`Product Supply Agreement to market, promote, distribute, sell, and
`
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`otherwise commercialize CT-P42 in the U.S., among other countries.
`
` Celltrion does not deny that, through Celltrion USA,
`
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`Celltrion will market, sell, and distribute CT-P42 in West
`Virginia.
`
`PROCEDURAL HISTORY
`III.
`Pursuant to 42 U.S.C. § 262(l)(8)(A), an applicant must
`provide notice to the reference product sponsor no later than 180
`days before the date of the first commercial marketing of the
`applicant’s product.
` Celltrion transmitted
`its Notice of Commercial Marketing (“NCM”) to Regeneron,
`
` Subsequently, Regeneron filed this lawsuit against
`Celltrion on November 8, 2023, asserting that Celltrion’s proposed
`
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`CT-P42 product would infringe at least 38 of its patents. ECF No.
`1.
`
`On December 28, 2023, Regeneron filed an emergency motion
`requesting either a schedule for preliminary injunction
`proceedings or an emergency status conference. ECF No. 45.
`Following the Scheduling Conference in this matter on January
`5, 2024, the Court issued an Order Setting the Briefing Schedule
`on Motions to Dismiss and Setting the Schedule for Preliminary
`Injunction Proceedings (“Scheduling Order”). ECF No. 61. The
`Scheduling Order required Regeneron to identify no more than eight
`patents that may be included in a motion for preliminary
`injunction. Id. at 3. On January 11, 2024 and pursuant to the
`Scheduling Order, Regeneron provided Celltrion a narrowed list of
`patents that may be included in a motion for preliminary
`injunction, see ECF No. 65, and on February 2, 2024, Regeneron
`further narrowed that list of patents that may be included in a
`motion for preliminary injunction, see ECF No. 93.
`On January 17, 2024, Celltrion filed a motion to dismiss for
`lack of personal jurisdiction or alternatively to transfer venue.
`ECF No. 68. Regeneron filed its opposition to that motion on
`February 19, 2024, ECF No. 104, and Celltrion filed a reply on
`February 26, 2024, ECF No. 114.
`
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`Pursuant to the Court’s Scheduling Order, Regeneron filed a
`motion for preliminary injunction against Celltrion on February
`22, 2024, based on the Product Patent and U.S. Patent 11,793,926
`(the “Sterile Barrier Patent”). ECF No. 108. Regeneron presumably
`did so because, pursuant to 42 U.S.C. § 262(k)(7)(A), approval of
`Celltrion’s aBLA may be made effective 180 days after the service
`of Celltrion’s NCM and as soon as Eylea’s regulatory exclusivity
`expires on May 18, 2024. Id. Regeneron’s motion asserted claims
`4, 7, 9, 11, and 14-17 (“Asserted Product Patent Vial Claims”) and
`claims 29, 32, 34, 36, and 39-42 (“Asserted Product Patent PFS
`Claims”) of the Product Patent (collectively, the “Asserted
`Product Patent Claims”) and claims 11-14 and 16-20 of the Sterile
`Barrier Patent (“Asserted Sterile Barrier Patent Claims”). Id.
`On March 7, 2024, Regeneron filed a supplemental motion for
`preliminary injunction as to claim 42 of the Product Patent in
`light of new data produced by Celltrion. Regeneron Suppl. PI Br.
`(ECF No. 129-2). Celltrion filed its opposition to Regeneron’s PI
`motion on March 21, 2024, Opp. (ECF No. 143-2), and Regeneron filed
`a reply on April 18, 2024, Reply (ECF No. 157-2).
`On May 15, 2024, the Court entered a stipulation under which
`Celltrion agreed to maintain the marketplace status quo and not
`launch its CT-P42 product before the Court denies Regeneron’s
`
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`motion for preliminary injunction against Celltrion or
`, whichever is earlier. ECF No. 177. On May 17, 2024, the
`Court held a scheduling conference. ECF No. 178.
`To streamline the issues in dispute in the Preliminary
`Injunction motions, Regeneron moved to withdraw its Motions for
`Preliminary Injunction with respect to the Sterile Barrier Patent
`on May 21, 2024. ECF No. 183.
`The Court has not held an evidentiary hearing on Regeneron’s
`motion for injunctive relief, and one is not necessary here. The
`Court originally scheduled a hearing on Regeneron’s motion for May
`2, 2024. On April 23, 2024, the parties filed a joint motion
`requesting “a status conference to discuss the logistics of the
`injunction hearings scheduled for May 2, 2024, including the length
`of the time of the hearings, and the Court’s preferences for the
`presentation of argument.” Joint Mot. for Status Conf. (MDL No.
`1:24-md-3103, ECF No. No. 9). The parties did not request or
`otherwise discuss the presentation of testimony or other evidence
`during the May 2 hearing in their April 23 submission. Id. On
`April 24, 2024, the Court continued the May 2 hearing in view of
`the multi-district litigation consolidation of this and several
`related proceedings as well as the scheduling of a separate
`criminal trial. Order Continuing May 2, 2024 Preliminary and
`
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`Permanent Injunction Hearings (MDL No. 1:24MD3103, ECF No.
`13). On May 17, the Court held a status conference in which all
`parties appeared, and no party objected to the cancellation of the
`preliminary injunction hearing, sought its reinstatement,3 or
`otherwise objected to proceeding on the papers. To the extent any
`party now argues that a hearing was necessary, the Court finds
`that the parties waived request to a hearing. See Baxter
`Healthcare Corp. v. Med. Lab'y Automation, Inc., 1994 WL 695521,
`at *2 (N.D. Ill. Dec. 9, 1994) (“Baxter did not request an
`evidentiary hearing or suggest that an evidentiary hearing was
`needed or would be preferable. . . . A party that rests on
`affidavits and other written submissions waives an evidentiary
`hearing.”); Sciele Pharma Inc. v. Lupin Ltd., 2012 WL 113004, at
`*3 (D. Del. Jan. 12, 2012). The Court thus resolves Regeneron’s
`motion for a preliminary injunction based on the parties’ written
`submissions and cited testimony. See Richmond Tenants Org., Inc.
`v. Kemp, 956 F.2d 1300, 1304 (4th Cir. 1992) (affirming preliminary
`injunction
`where
`“the
`district
`court
`issued
`a
`
`3 Even a cursory review of the docket in this and the related cases
`reveals the parties are no stranger to motions practice. The lack
`of a motion to convene an evidentiary hearing is quite telling.
`
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`preliminary injunction prohibiting evictions without prior notice
`and a hearing and enjoining defendants”).
`IV.
`FACTUAL BACKGROUND
`
`A. Declarants
`Regeneron filed declarations from two expert witnesses, Dr.
`Bernhardt Trout and Dr. Sean Sheridan, and two fact witnesses, Mr.
`Kevin Clark and Dr. Kenneth Graham, in support of Regeneron’s
`preliminary injunction motion regarding the Product Patent.
`Celltrion deposed three of Regeneron’s witnesses but declined to
`take the deposition of Dr. Kenneth Graham, a fact witness. See
`Regeneron’s Opp. to Celltrion’s Mot. to Strike at 9-10 (ECF No.
`166). Celltrion presented declarations from three expert
`witnesses relevant to the Product Patent: Dr. Peter Tessier, Dr.
`James Malackowski, and Dr. Christine Kay. Regeneron deposed all
`Celltrion’s witnesses.
`
`1. Regeneron’s Declarants
`Dr. Bernhardt Trout, Ph.D., addressed the infringement and
`validity of the Product Patent. Dr. Trout also provided expert
`testimony about infringement and validity of the Product Patent at
`the Mylan trial. Dr. Trout is a Professor of Chemical Engineering
`at the Massachusetts Institute of Technology and holds a Ph.D. in
`chemical engineering. Trout Decl. ¶¶ 16-17 (ECF No. 108-4). At
`
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`MIT, Dr. Trout performs pharmaceutical development and
`manufacturing research on biopharmaceutical (e.g., protein-based)
`therapeutics and has worked on approximately fifty biologic
`therapeutics. Id. ¶¶ 19-20.
`Dr. Sean Sheridan is a Vice President at Charles River
`Associates, an international business consulting firm, and has a
`Ph.D. in genetics as well as an MBA with concentrations in finance
`and economics from the University of Chicago. Sheridan Decl. ¶¶ 1-
`2.
`Dr. Sheridan’s declaration addressed whether Regeneron would
`be irreparably harmed by market entry of Eylea biosimilars prior
`to expiry of the asserted patents. Dr. Sheridan’s previous
`experience has included the quantification of economic damages,
`and he has experience in modeling and valuation in a variety of
`
`intellectual property matters. Id. ¶¶ 3-5.
`
`Kevin Clark is Vice President of Regeneron’s Ophthalmology
`Commercial Business Unit, a role he has held since 2020. Clark
`Decl. ¶ 1. Mr. Clark’s focus at Regeneron has been on the
`commercialization of Eylea and Eylea HD. Id. ¶ 3. Mr. Clark’s
`declaration addressed the effect of biosimilar entry on Regeneron
`and its Eylea product.
`Dr. Kenneth Graham, Ph.D., is a named inventor on the Product
`Patent. Dr. Graham has worked at Regeneron for over twenty-two
`
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`years and is currently the Executive Director of Formulation
`Development at Regeneron. Graham Decl. ¶ 1 (ECF No. 157-4). He
`joined Regeneron’s Formulation Development group in 2005, when the
`group was engaged in aflibercept formulation stability studies.
`Id. ¶ 2. Dr. Graham’s declaration addresses several internal
`stability studies Regeneron’s scientists conducted on aflibercept.
`
`2. Celltrion’s Declarants
`Celltrion filed an expert declaration from Peter M. Tessier,
`Ph.D. addressing the validity of the Product Patent. Dr. Tessier
`is a Professor in the Departments of Pharmaceutical Sciences and
`Chemical Engineering and Biomedical Engineering at the University
`of Michigan and holds a Ph.D. in chemical engineering. Tessier
`Decl. ¶¶ 10-11 (ECF No. 142-5). At the University of Michigan,
`Dr. Tessier performs research on the formulation of biologics,
`including research on formulations of protein-based biologics.
`Id. ¶ 10.
`Celltrion also filed an expert declaration from James
`Malackowski addressing whether Regeneron would be irreparably
`harmed by the launch of Celltrion’s biosimilar product. Mr.
`Malackowski is the co-founder and Senior Managing Director of Ocean
`Tomo, LLC, which provides consulting and financial expert services
`related to clients’ intellectual property. Malackowski Decl. ¶ 1
`
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`(ECF No. 142-12).
`Celltrion’s third expert declaration was from Dr. Christine
`Kay, M.D. Dr. Kay is a licensed ophthalmologist with experience
`in intravitreal injections, and has performed thousands of such
`injections over her career. Kay Tr. 20:21-21:4 (ECF No. 157-3,
`Ex. 3). Dr. Kay provided testimony regarding ophthalmologists’
`reasons for administering an ophthalmic drug product, which
`include the product’s safety and efficacy. ECF No. 142-22, Kay
`Decl. ¶¶ 39-47 (ECF No. 142-22).
`B. Product Patent
`The United States Patent and Trademark Office (“USPTO”)
`issued the Product Patent, titled “VEGF Antagonist Formulations
`Suitable for Intravitreal Administration,” on August 10, 2021, to
`Regeneron Pharmaceuticals, Inc. upon assignment from inventors
`Eric Furfine, Daniel Dix, Kenneth Graham, and Kelly Frye. Product
`Patent, Cover Page (ECF No. 108-11, Trout Ex. 65). The Product
`Patent claims priority through continuation and divisional
`applications to Provisional Patent Application No. 60/814,484,
`filed June 16, 2006. Id.
`This Court has previously addressed Regeneron’s Eylea product
`and the Product Patent which Regeneron asserts in this preliminary
`injunction proceeding. In Regeneron v. Mylan, this Court
`
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`Claim 1
`(unasserted)
`
`previously held that the Product Patent was not invalid and that
`Mylan’s Eylea biosimilar, “M710,” infringed claims 4, 7, 9, 11,
`and 14-17 of the Product Patent. Mylan, 2024 WL 382495, at *25-
`33, 46-70.
`The following table lists the claims Regeneron contends that
`Celltrion infringes, as well as the claims from which they depend.
`Regeneron PI Br. at 5-8; Regeneron Suppl. PI Br. at 1.
`Claims of the Product Patent
`1. A vial comprising an ophthalmic formulation
`suitable for intravitreal
`administration that comprises:
`a vascular endothelial growth factor (VEGF)
`antagonist
`an organic co-solvent,
`a buffer, and
`a stabilizing agent,
`wherein said VEGF antagonist fusion protein is
`glycosylated and comprises
`amino acids 27-457 of SEQ ID NO:4; and
`wherein at least 98% of the VEGF antagonist is
`present in native
`conformation following storage at 5° C. for two
`months as measured by size
`exclusion chromatography.
`2. The vial of claim 1, wherein the concentration
`of said VEGF antagonist
`fusion protein is 40 mg/ml, and wherein said
`organic co-solvent comprises
`polysorbate.
`4. The vial of claim 2, wherein said organic co-
`solvent comprises about
`0.03% to about 0.1% polysorbate 20.
`5. The vial of claim 2, wherein said organic co-
`solvent comprises 0.01% to
`3% polysorbate 20.
`
`Claim 2
`(unasserted)
`
`Claim 4
`
`Claim 5
`(unasserted)
`
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`Claim 7
`
`Claim 9
`
`Claim 10
`(unasserted)
`
`Claim 11
`
`Claim 14
`
`Claim 15
`
`Claim 16
`
`Claim 17
`
`Claim 26
`(unasserted)
`
`7. The vial of claim 5, wherein said buffer
`comprises 5-25 mM buffer.
`9. The vial of claim 5, wherein said buffer
`comprises a pH about 6.2-6.3.
`10. The vial of claim 5, wherein said stabilizing
`agent comprises a sugar.
`11. The vial of claim 10, wherein said sugar is
`selected from the group
`consisting of sucrose, sorbitol, glycerol,
`trehalose, and mannitol.
`14. The vial of claim 5, wherein said VEGF
`antagonist fusion protein is
`glycosylated at asparagine residues corresponding
`to asparagine residues
`62, 94, 149, 222 and 308 of SEQ ID NO: 4.
`15. The vial of claim 5, wherein said formulation
`is capable of providing a
`turbidity of 0.01 or lower at OD405 after 2 month
`storage at 5° C.
`16. The vial of claim 5, wherein at least 99% of
`said VEGF antagonist
`fusion protein is present in native conformation
`after 2 month storage at 5°
`C. as measured by size exclusion chromatography.
`17. The vial of claim 5, wherein at least 98% of
`said VEGF antagonist
`fusion protein is present in native conformation
`following storage at 5° C.
`for 24 months as measured by size exclusion
`chromatography.
`26. A pre-filled syringe comprising an ophthalmic
`formulation suitable for intravitreal
`administration comprising:
`a vascular endothelial growth factor ( VEGF )
`antagonist fusion protein,
`an organic co-solvent,
`a buffer, and
`
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`IN RE: AFLIBERCEPT PATENT LITIGATION
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`a stabilizing agent;
`wherein said VEGF antagonist fusion protein is
`glycosylated and comprises amino acids 27-457 of
`SEQ ID NO:4; and
`wherein at least 98 % of said VEGF antagonist
`fusion protein is present in native conformation
`following storage at 5° C. for two months as
`measured by size exclusion chromatography.
`27. The pre-filled syringe of claim 26, wherein
`the concentration of said VEGF antagonist fusion
`protein is 40 mg/ml, and wherein said organic co
`- solvent comprises polysorbate.
`29. The pre-filled syringe of claim 27, wherein
`said organic co - solvent comprises about 0.03 %
`to about 0.1 % polysorbate 20.
`30. The pre - filled syringe of claim 27, wherein
`said organic co-solvent comprises 0.01 % to 3 %
`polysorbate 20.
`32. The pre-filled syringe of claim 30, wherein
`said buffer comprises 5-25 mM buffer.
`34. The pre-filled syringe of claim 30 , wherein
`said buffer comprises a pH about 6.2-6.3.
`35. The pre-filled syringe of claim 30, wherein
`said stabilizing agent comprises a sugar.
`36. The pre-filled syringe of claim 35, wherein
`said sugar is selected from the group consisting
`of sucrose, sorbitol, glycerol, trehalose, and
`mannitol.
`39. The pre-filled syringe of claim 30, wherein
`said VEGF antagonist fusion protein is
`glycosylated at asparagine residues corresponding
`to asparagine residues 62 , 94 , 149 , 222 and
`308 of SEQ ID NO:4.
`40. The pre-filled syringe of claim 30 , wherein
`said formulation is capable of providing a
`turbidity of 0.01 or lower at OD405 after 2 month
`storage at 5° C.
`41. The pre-filled syringe of claim 30, wherein
`at least 99% of said VEGF antagonist fusion
`protein is present in native conformation after 2
`month storage at 5° C. as measured by size
`exclusion chromatography.
`
`Claim 27
`(unasserted)
`
`Claim 29
`
`Claim 30
`(unasserted)
`Claim 32
`Claim 34
`Claim 35
`(unasserted)
`Claim 36
`
`Claim 39
`
`Claim 40
`
`Claim 41
`
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`Claim 42
`
`42. The pre-filled syringe of claim 30, wherein
`at least 98% of said VEGF antagonist fusion
`protein is present in native conformation
`following storage at 5° C. for 24 months as
`measured by size exclusion chromatography.
`The meaning and validity of a patent are evaluated from the
`perspective of a Person of Ordinary Skill in the Art (“POSA”).
`Neither party has advanced a definition of the POSA at this stage
`of litigation and the definition does not seem to be an issue of
`dispute at this time. As such, the Court adopts the definition of
`the POSA in this case that it adopted in Mylan:
`[T]he POSA ‘would be a professional with a master’s
`degree at least in a relevant field, so a technical
`field directly relevant to formulations here.’ Tr.
`2092:6-17 (Trout); PDX-9.002 (explaining that the
`POSA ‘would have held an advanced degree, such as
`a Master's in a biopharmaceutical science, or a
`related discipline, such as chemical engineering,
`and several years of experience in the development
`of biologics products. Alternatively, the POSA
`could have a Ph.D. in such discipline and less
`experience. The POSA may collaborate with others,
`including a medical doctor with experience treating
`ophthalmic diseases.’).
`Mylan, 2024 WL 382495, at *22-23.
`C. Prior Claim Constructions
`This Court already construed two claim terms in the earlier
`Mylan litigation. In Mylan, “[t]he Court construed ‘organic co-
`solvent’ to mean ‘an organic substance added to the primary solvent
`to increase the solubility of the solute, here a VEGF
`
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`antagonist’ . . . [and] construed ‘native conformation’ to mean
`‘the original intact form of the VEGF antagonist, which is a form
`that does not exhibit chemical or physical instability.’” Mylan,
`2024 WL 382495, at *17 (quoting Mylan, C.A. No. 1:22-cv-61, ECF
`No. 427 at 20, 25-26). The parties have applied those
`constructions in these preliminary injunction proceedings, and the
`Court applies those constructions here as well.
`D. Infringement
`As detailed below, the Court finds that Celltrion’s CT-P42
`product meets each and every limitation of the Asserted Product
`Patent Claims; thus, Regeneron is likely to succeed on infringement
`of the Asserted Product Patent Claims.
`Only Regeneron submitted an expert declaration on the topic
`of infringement of the Asserted Product Patent Claims. Regeneron’s
`expert, Dr. Trout, explained that CT-P42 infringes all of the
`Asserted Product Patent Claims. Trout Decl. App. A. Celltrion
`did not dispute infringement or submit a declaration from a non-
`infringement expert. Thus, Dr. Trout’s infringement opinion
`remains unrebutted, and all limitations are undisputed between the
`parties. As explained below, the Court credits the opinions of
`Dr. Trout on issues involving infringement of the Asserted Product
`Patent Claims.
`
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`E. Validity
`Celltrion raises two grounds of invalidity with respect to
`the Product Patent: obviousness-type double patenting and written
`description. Opp. at 6-17. Both parties submitted expert
`declarations addressing validity. Dr. Trout submitted an expert
`declaration for Regeneron, and Dr. Tessier submitted an expert
`declaration for Celltrion.
`
`F. Celltrion May Launch CT-P24 in the Absence of an
`Injunction
`Celltrion expects to receive FDA approval for CT-P42 by
`. Sheridan Ex. C-3, at -764. (ECF No. 108-22). If that
`expectation holds, absent an injunction, Celltrion would be
`permitted to launch CT-P42 following the expiration on
`, of the stipulated temporary restraining order entered by
`this Court on May 14. ECF No. 177.
`
`See Malackowski Decl. ¶ 63; Opp. 22. Regeneron has sought a
`preliminary injunction to prevent Celltrion from producing,
`marketing, or selling their allegedly infringing product until
`after a decision after a trial on the merits.
`
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`G. CT-P42’s Launch Will Irreparably Harm Regeneron
`As detailed below, the Court finds that Celltrion’s launch of
`CT-P42 will irreparably harm Regeneron. Regeneron’s expert, Dr.
`Sheridan, submitted a declaration setting forth the anticipated
`harms that Regeneron would face if a biosimilar such as CT-P42
`were to launch, including harm to market share, pricing, payor
`relationships, reputation, and research and development funding
`(which the Court does not find as a basis for irreparable harm
`here). The Vice President of Regeneron’s Ophthalmology Commercial
`Business, Mr. Clark, also submitted a declaration detailing these
`anticipated harms. As explained below, the Court credits the
`opinions of Dr. Sheridan and testimony of Mr. Clark on issues
`involving irreparable harm.
`Regeneron has demonstrated that it will suffer irreparable
`harm that a damages award could not fully remedy. A future damages
`award cannot compensate Regeneron adequately for the harm to its
`sales, price, relationships with payors and reputational harm.
`These harms, while nearly certain to occur, are all but impossible
`to fully quantify. They are also generally impossible to reverse.
`The Court will analyze each type of harm in detail below.
`
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`IN RE: AFLIBERCEPT PATENT LITIGATION
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