Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 1 of 92
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE SOUTHERN DISTRICT OF NEW YORK
`
`
`
`
`CASE NO.:
`
`
`JURY TRIAL DEMANDED
`
`
`COMPLAINT
`
`
`
`
`REGENERON PHARMACEUTICALS, INC.
`
`
`Plaintiff,
`
`
`
`v.
`
`
`NOVARTIS PHARMA AG, NOVARTIS
`TECHNOLOGY LLC, NOVARTIS
`PHARMACEUTICALS CORPORATION,
`VETTER PHARMA INTERNATIONAL
`GMBH
`
`
`Defendants.
`
`Plaintiff Regeneron Pharmaceuticals, Inc. (“Regeneron”) files this Complaint against
`
`Defendants, Novartis Pharma AG, Novartis Technology LLC, and Novartis Pharmaceuticals
`
`Corporation (collectively, “Novartis”) and Vetter Pharma International GmbH (“Vetter”), and
`
`alleges, upon knowledge as to itself and otherwise upon information and belief, as follows:
`
`NATURE OF ACTION
`
`1.
`
`Plaintiff Regeneron’s EYLEA® (aflibercept) injection (“EYLEA”) is an innovative
`
`biologic drug for the treatment of a variety of severe eye diseases.
`
`2.
`
`Defendant Novartis developed and recently launched BEOVU® (brolucizumab-
`
`dbll) injection (“BEOVU”), which competes against EYLEA to treat a certain eye disease.
`
`Novartis, together with Genentech, Inc. (“Genentech”), also co-developed LUCENTIS®
`
`(ranibizumab) injection (“LUCENTIS”), which competes against EYLEA to treat most of the
`
`same eye diseases. Novartis markets LUCENTIS outside of the United States, and benefits from
`
`the sales of LUCENTIS in the United States through its significant financial stake in Roche
`
`
`
`
`Novartis Exhibit 2057.001
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 2 of 92
`
`
`
`Holding AG (“Roche”), the parent company of Genentech, which markets LUCENTIS in the
`
`United States.1 Defendant Vetter is an essential supply chain provider of drug “filling” services
`
`and is the exclusive filler for Novartis’s LUCENTIS prefilled syringe (“PFS”) product. Upon
`
`information and belief, Vetter will be the filler for Novartis’s BEOVU PFS once it launches in the
`
`United States. Vetter also has a longstanding relationship with Regeneron, both as a filler for
`
`EYLEA vials and as a prior development partner for an EYLEA PFS.
`
`3.
`
`Defendant Novartis, unwilling to compete on the clinical merits of LUCENTIS or
`
`BEOVU against EYLEA, has done everything in its power to try to stop EYLEA through
`
`anticompetitive means. BEOVU’s launch has been riddled with serious safety issues, and
`
`LUCENTIS is a less effective treatment than EYLEA for certain diabetic eye diseases and requires
`
`more frequent injections (per the FDA-approved label) at a time when in-patient trips to medical
`
`doctors are difficult with the COVID-19 pandemic.2 Novartis has therefore resorted to various
`
`unlawful means, including the enforcement of a fraudulently procured United States patent and an
`
`anticompetitive licensing and settlement agreement with Vetter, all as part of a scheme to attempt
`
`to monopolize the market and/or unreasonably restrain competition for PFS ophthalmic drug
`
`treatments. Defendants’ purpose and intent throughout this scheme has been to prevent, deter, or
`
`at least delay the competitive launch of EYLEA PFS for years, to artificially inflate Regeneron’s
`
`costs of entry, and now to stop Regeneron altogether from competing in the U.S. market with
`
`
`1
`All references to LUCENTIS refer to the product that was co-developed by Novartis and is
`marketed by Novartis outside the United States and by Genentech inside the United States.
`
`2
`Compare U.S. Food and Drug Administration, Lucentis® (ranibizumab injection), “Highlights of
`Prescribing
`Information,
`available
`at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125156s111lbl.pdf with U.S. Food and Drug
`Administration, Eylea®
`(aflibercept), “Highlights of Prescribing
`Information, available at
`https://www.regeneron.com/sites/default/files/EYLEA_FPI.pdf.
`
`
`
`2
`
`Novartis Exhibit 2057.002
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 3 of 92
`
`
`
`EYLEA PFS. In addition to Regeneron, physicians and patients have been the victims of this
`
`scheme because Novartis’s and Vetter’s actions are aimed at limiting the availability of the most
`
`effective and convenient ophthalmic PFS drug treatment—EYLEA PFS.
`
`4.
`
`By this action for injunctive relief and damages, Regeneron seeks to stop
`
`Defendants Novartis and Vetter from continuing their illegal conduct in violation of Sections 1
`
`and 2 of the Sherman Antitrust Act, 15 U.S.C. §§ 1 and 2.
`
`INTRODUCTION
`
`5.
`
`Regeneron’s EYLEA and Novartis’s LUCENTIS and BEOVU are competing
`
`drugs that treat certain eye diseases involving overproduction of a naturally occurring protein in
`
`the body called vascular endothelial growth factor (“VEGF”). This VEGF overproduction can
`
`cause vision loss and even blindness, and many millions of patients suffer from VEGF-related eye
`
`diseases.
`
`6.
`
`As “anti-VEGF” drugs, EYLEA, LUCENTIS, and BEOVU must be injected with
`
`regular frequency into a patient’s eye. The frequency, manner, and safety of injection are important
`
`factors in the success of treatment, and the method of administration is therefore significant. In
`
`that regard, EYLEA and LUCENTIS were historically sold only in vial form and ultimately loaded
`
`into a separate needle or syringe for injection. Recently, however, the market for anti-VEGFs has
`
`converted from vial to PFS, which is a more accurate and more convenient method of
`
`administration that carries a lower risk of introducing foreign particles into the eye, which can
`
`cause severe complications such as endophthalmitis. LUCENTIS and EYLEA are by far the
`
`primary approved anti-VEGF PFS available in the United States.3
`
`7.
`
`There are numerous challenges associated with commercializing a PFS with a
`
`
`3
`While Macugen received FDA approval in 2004 for a prefilled syringe to treat one VEGF-related
`eye disease only, it is also an older, less effective treatment that is rarely prescribed anymore, if at all.
`3
`
`
`
`Novartis Exhibit 2057.003
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 4 of 92
`
`
`
`complex biologic drug such as EYLEA or LUCENTIS. For example, there are a limited number
`
`of companies that can fill the syringe with the drug in accordance with the required sterile
`
`conditions, and the existing “fillers” have limited capacity. Vetter is the leading PFS filler and is
`
`the exclusive PFS filler for Novartis’s LUCENTIS PFS. Regeneron and Vetter also have had a
`
`long-standing relationship. For many years, Vetter has provided non-exclusive filling services to
`
`Regeneron for EYLEA in vial form. More specifically, starting in 2005, Regeneron and Vetter
`
`also embarked on a collaboration to commercialize an EYLEA PFS. This successful collaboration
`
`led to regulatory approval for EYLEA PFS in Australia in 2012.
`
`8.
`
`Unbeknownst to Regeneron, however, as Regeneron and Vetter were jointly
`
`working to commercialize an EYLEA PFS, Novartis was pursuing its own mission in 2013 to
`
`fraudulently procure a United States patent claiming a PFS containing any anti-VEGF drug,
`
`including EYLEA, which Novartis and Vetter would soon use to unreasonably restrain
`
`Regeneron’s ability to compete. Given that the prior art already described and disclosed such a
`
`PFS, Novartis could secure its patent only by ensuring that the U.S. Patent and Trademark Office
`
`(“USPTO”) was not aware of that prior art. And Novartis did just that. By deliberately withholding
`
`material prior art from the USPTO, Novartis succeeded in obtaining a patent—U.S. Patent No.
`
`9,220,631 (the “’631 Patent”)—broadly claiming a PFS with any anti-VEGF, including EYLEA.4
`
`As pled in detail below, specific Novartis employees involved in the prosecution of the ’631 Patent
`
`knew of the omitted prior art and also knew the omitted prior art was material because of multiple
`
`decisions by a set of USPTO examiners in a separate patent application covering overlapping
`
`subject matter that Novartis ultimately abandoned. In order to gain allowance of the ’631 Patent,
`
`the Novartis employees made a deliberate decision to withhold the prior art from the different
`
`
`4
`The ’631 Patent specifically identifies EYLEA and states that “[a]flibercept is the preferred non-
`antibody VEGF antagonist for use with the invention.” ’631 Patent at Col. 6, ll. 42-43.
`4
`
`
`
`Novartis Exhibit 2057.004
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 5 of 92
`
`
`
`USPTO examiner that was reviewing the application for the ’631 patent.
`
`9.
`
`Further unknown to Regeneron, Novartis and Vetter were vying to control the
`
`patent application underlying the ’631 Patent. Using this dispute as a pretense, Novartis and Vetter
`
`entered into an anticompetitive conspiracy around 2013 to unreasonably restrain competition in
`
`anti-VEGF PFS treatments for ophthalmic diseases. Novartis effectively used the settlement
`
`process for the then-pending application that would become the ’631 Patent to obtain control and
`
`influence over Vetter’s PFS filling services so as to inhibit anti-VEGF rivals like Regeneron. This
`
`“settlement” provided Vetter with a “co-exclusive” license to what would become Novartis’s
`
`fraudulently procured ʼ631 Patent and the exclusive right to grant sublicenses. The quid pro quo
`
`was that Novartis extracted a lucrative economic interest in Vetter’s PFS filling services in the
`
`form of Vetter’s assent to place onerous and anticompetitive restrictions on Novartis’s rivals—like
`
`Regeneron—that had been working with Vetter all along. This anticompetitive agreement co-opted
`
`Vetter and enabled Novartis to exert influence over Vetter’s current and future customer
`
`relationships so that Novartis could undermine competitors’ efforts to develop and sell competing
`
`anti-VEGF PFS drugs. As for Vetter, it stood to benefit from this agreement by becoming the sole
`
`filler for all anti-VEGF PFS drugs—since Novartis would wield its fraudulently procured ʼ631
`
`Patent against any company that tried to compete by using a different PFS filler.
`
`10.
`
`Immediately following
`
`its “settlement” with Novartis, and despite
`
`the
`
`approximately eight year long collaboration with Regeneron to commercialize an EYLEA PFS,
`
`Vetter did just as Novartis had intended. Vetter abruptly reversed course with Regeneron in 2013.
`
`Vetter chose the path of illicit profits by colluding with Novartis to control the supply of anti-
`
`VEGF PFS treatments. Specifically, Vetter contacted Regeneron in October 2013, claimed that
`
`Novartis had a pending patent application, and demanded that Regeneron take a sublicense to the
`
`
`
`5
`
`Novartis Exhibit 2057.005
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 6 of 92
`
`
`
`yet to be issued ’631 Patent before Vetter would continue their collaboration on EYLEA PFS—
`
`even though the ’631 Patent would not even issue for two more years. As a condition of
`
`continuing their work on EYLEA PFS, Vetter also required that Regeneron submit to two
`
`anticompetitive restrictions: (1) Regeneron must use Vetter as its exclusive PFS filler for the next
`
`20 years—i.e., for the entire life of Novartis’s yet to be issued ’631 Patent; and (2) Regeneron
`
`must never challenge the validity or enforceability of Novartis’s yet to be issued ’631 Patent.
`
`11.
`
`Regeneron could not—and did not—accept this offer. First, the unlawful “no
`
`challenge” requirement was unacceptable given Regeneron’s own role in developing EYLEA PFS
`
`and the extensive prior art (including the prior art Novartis deliberately withheld from the USPTO
`
`during prosecution of the ’631 Patent) showing that the claimed PFS in Novartis’s patent was not
`
`patentable. Separately, Regeneron could not agree to be locked into an exclusive supply
`
`arrangement with Vetter for 20 years because it would inhibit the competitiveness of EYLEA PFS.
`
`Vetter is the capacity-constrained exclusive supplier of LUCENTIS PFS and Regeneron had
`
`certain quality concerns about Vetter as its sole PFS filler—two issues that Vetter failed to address.
`
`Consequently, Regeneron had no choice but to decline Vetter’s (and Novartis’s) unlawful
`
`demands.
`
`12.
`
`The overarching goal of Novartis’s and Vetter’s conspiracy has been to control—
`
`and unreasonably restrain—competition in anti-VEGF PFS treatments for certain ophthalmic
`
`diseases. Their initial plan was to have all anti-VEGF PFS drugs run through Novartis and the PFS
`
`filling services for those drugs to run exclusively through Vetter. Regeneron’s EYLEA has been
`
`the only real competitive threat to LUCENTIS PFS, giving both Novartis and Vetter (now as a co-
`
`conspirator) significant economic motives to lock up Regeneron’s EYLEA PFS business by
`
`leveraging Novartis’s fraudulently procured ’631 Patent. To this end, Novartis and Vetter sought
`
`
`
`6
`
`Novartis Exhibit 2057.006
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 7 of 92
`
`
`
`to hold Regeneron captive to Vetter’s limited-supply PFS filling services for 20 years as a
`
`condition of Regeneron obtaining a covenant that Novartis (or Vetter) would not sue Regeneron
`
`on the fraudulently procured ’631 Patent. But when Regeneron rejected Novartis’s and Vetter’s
`
`unlawful efforts to coerce Regeneron into an exclusive arrangement, Novartis and Vetter conspired
`
`to keep EYLEA PFS out of the market altogether.
`
`13.
`
`To Novartis’s benefit, Novartis and Vetter agreed to deny Regeneron access to any
`
`of Vetter’s essential PFS filling services for EYLEA PFS. Not only did this denial represent an
`
`abrupt change in Vetter’s collaboration with Regeneron to commercialize EYLEA PFS, but it also
`
`was in stark contrast to Vetter’s then and current relationship with Regeneron filling EYLEA vials
`
`without exclusivity. As for commercialization of the EYLEA PFS, Novartis and Vetter knew that
`
`Regeneron would need to start over with few to no PFS filler options for this critical aspect of the
`
`supply chain, resulting in years of delay and additional, substantial, and unnecessary costs. And
`
`that is exactly what happened to Regeneron.
`
`14.
`
`Novartis and Vetter did not stop there, however. They doubled down on their
`
`conspiracy to limit competition from EYLEA PFS after the ’631 Patent issued in December 2015.
`
`With the fraudulently procured ’631 Patent in hand by that point, Vetter again demanded the same
`
`anticompetitive terms (an exclusive filling agreement and no challenge clause) from Regeneron in
`
`late 2017. Regeneron again refused. Two and a half years later, after Regeneron had successfully
`
`created a new supply and filler chain for EYLEA PFS and launched it in the United States, and
`
`when Novartis’s BEOVU’s safety problems came to light, Novartis took the next step in this illicit
`
`scheme. On June 19, 2020, Novartis filed a patent infringement complaint at the U.S. International
`
`Trade Commission (“ITC”) asserting its fraudulently procured ’631 Patent and seeking an
`
`exclusion order barring importation of EYLEA PFS components into the United States. Novartis
`
`
`
`7
`
`Novartis Exhibit 2057.007
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 8 of 92
`
`
`
`also filed a companion infringement complaint in the Northern District of New York (“NDNY”)
`
`seeking damages and injunctive relief for alleged infringement of ’631 Patent. Despite knowing
`
`that the ’631 Patent was fraudulently procured and unenforceable, Novartis filed multiple
`
`litigations in yet another attempt to block EYLEA PFS from the U.S. market, or at the very least,
`
`to artificially increase Regeneron’s costs even more by erecting anticompetitive barriers to sale.
`
`15.
`
`Defendants’ anticompetitive conduct has injured and continues to injure patients,
`
`physicians, and Regeneron. Instead of competing on the merits, Novartis and Vetter have
`
`concocted numerous anticompetitive obstacles to initially try to stop Regeneron from launching—
`
`and now from selling—EYLEA PFS. By forcing Regeneron to navigate around artificial and
`
`unlawful barriers, Defendants have delayed EYLEA PFS by years in coming to the U.S. market.
`
`Defendants imposed additional, substantial, and unnecessary costs on Regeneron to establish a
`
`reliable alternative supply and filler chain in order to commercialize EYLEA PFS. Now
`
`Defendants are forcing Regeneron to spend time and limited resources defending an ITC action
`
`and a patent infringement lawsuit based on a fraudulently procured patent, and would have
`
`Regeneron invest millions of dollars and months attempting to develop a contingent supply of
`
`EYLEA in vial form to hedge against the possibility that Novartis obtains an exclusion order from
`
`the ITC.
`
`16. Worst of all, if Novartis’s unlawful efforts succeed, patients and physicians will be
`
`deprived of EYLEA PFS altogether. Novartis will regain its monopoly over anti-VEGF PFS
`
`treatments for ophthalmic diseases and Vetter will remain the sole PFS filler for those treatments.
`
`Tellingly, in its ITC submissions, Novartis does not even attempt to claim that any alternative anti-
`
`VEGF PFS exists for EYLEA PFS other than LUCENTIS PFS. And the only other potential near-
`
`term PFS entrant is another Novartis drug, BEOVU, which has serious safety issues. Through the
`
`
`
`8
`
`Novartis Exhibit 2057.008
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 9 of 92
`
`
`
`anticompetitive enforcement of the fraudulently procured ’631 Patent, Novartis is trying to force
`
`physicians and patients to make a difficult choice between LUCENTIS PFS, which offers
`
`numerous advantages through its PFS delivery method, and the EYLEA vial, a medication that is
`
`regarded by many physicians and patients as a superior anti-VEGF eye disease treatment but is
`
`administered using a non-preferred method. This is particularly harmful because physicians are
`
`naturally reluctant to switch a patient who is responding well to one anti-VEGF to another anti-
`
`VEGF treatment. In a competitive marketplace, physicians and patients would not have to make
`
`this difficult tradeoff. They should continue to have access to an anti-VEGF PFS that combines all
`
`of these medical advantages in one—Regeneron’s EYLEA PFS.
`
`17.
`
`Regeneron is compelled to bring this lawsuit to stop Defendants’ unlawful behavior
`
`and to hold Defendants accountable in front of a jury in a public court of law for their
`
`anticompetitive conduct.
`
`PARTIES TO ACTION
`
`18.
`
`Plaintiff Regeneron is a corporation organized and existing under the laws of the
`
`State of New York with its principal place of business located at 777 Old Saw Mill River Road,
`
`Tarrytown, New York 10591. Regeneron is in the business of inventing, developing,
`
`manufacturing, and marketing a variety of innovative pharmaceutical products, including EYLEA
`
`and EYLEA PFS.
`
`19.
`
`Defendant Novartis Pharma AG is a corporation organized and existing under the
`
`laws of Switzerland, with an office and a place of business located at Forum 1 Novartis Campus,
`
`CH-4056 Basel, Switzerland.
`
`20.
`
`Defendant Novartis Pharmaceuticals Corporation is a corporation organized and
`
`existing under the laws of the state of Delaware with its principal place of business located at One
`
`
`
`9
`
`Novartis Exhibit 2057.009
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 10 of 92
`
`
`
`Health Plaza, East Hanover, New Jersey 07936. Novartis Pharmaceuticals Corporation is an
`
`affiliate of Novartis Pharma AG.
`
`21.
`
`Defendant Novartis Technology LLC is a corporation organized and existing under
`
`the laws of the state of Delaware with its principal place of business located at One Health Plaza,
`
`East Hanover, New Jersey 07936.
`
`22.
`
`Defendant Vetter is a company organized and existing under the laws of Germany,
`
`with its principal place of business located at Eywiesenstrasse 5, 88212 Ravensburg, Germany.
`
`Vetter also operates facilities located in Des Plaines and Skokie, Illinois.5
`
`JURISDICTION AND VENUE
`
`23.
`
`This Court has subject matter jurisdiction over all claims asserted against
`
`Defendants pursuant to 28 U.S.C. § 1331, 28 U.S.C. § 1337(a), 15 U.S.C. § 4, 15 U.S.C. § 15, and
`
`15 U.S.C. § 26.
`
`24.
`
`This Court has personal jurisdiction over Defendants under the U.S. Constitution
`
`and nationwide contacts under Section 12 of the Clayton Act, 15 U.S.C. § 22.
`
`25.
`
`Venue is proper in this District under Section 12 of the Clayton Act, 15 U.S.C. §
`
`22, and under 28 U.S.C. § 1391(b) and (c).
`
`26.
`
`For personal jurisdiction and venue purposes, Defendants can be found in, and
`
`transact business in, this District, including through the marketing and sale of LUCENTIS PFS
`
`and BEOVU. Defendants’ unlawful behavior was specifically intended to, has had, and will
`
`continue to have an anticompetitive effect and impact on Regeneron and U.S. consumers in this
`
`District, and elsewhere.
`
`
`5
`Vetter U.S. Locations, available at https://www.vetter-pharma.com/en/about-us/locations/chicago-
`skokie (last visited July 11, 2020).
`
`
`
`10
`
`Novartis Exhibit 2057.010
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 11 of 92
`
`
`
`INTERSTATE COMMERCE
`
`27.
`
`The commercialization, development, manufacturing, marketing, sale, and
`
`distribution of EYLEA, LUCENTIS, and BEOVU occurs in interstate commerce.
`
`FACTUAL BACKGROUND6
`
`Anti-VEGF Drugs for Treating Ophthalmic Diseases
`
`Anti-VEGF drugs, like EYLEA and LUCENTIS, are used to treat certain
`
`A.
`
`28.
`
`ophthalmic diseases that can cause vision loss or blindness, including Wet Age-Related Macular
`
`Degeneration, Diabetic Retinopathy, Diabetic Macular Edema, and Macular Edema following
`
`Retinal Vein Occlusion. Another anti-VEGF drug, BEOVU, was recently approved for the
`
`treatment of Wet Age-Related Macular Degeneration only.
`
`29.
`
`These complex biologics work by targeting over-produced VEGF proteins and
`
`blocking or inhibiting them. This reduces abnormal blood vessel growth and leakage in the eye,
`
`which helps to stabilize vision loss, and in some cases, can even reverse vision loss and restore
`
`sight. Anti-VEGF treatments are only effective at maintaining or improving vision when
`
`administered regularly on a continuing basis.
`
`30.
`
`Patients receive treatment for these ophthalmic diseases in a physician’s office. An
`
`ophthalmologist (typically a retinal specialist) must administer anti-VEGF drugs via syringe with
`
`an injection near the retina in the back of the eye, known as an “intravitreal injection.”
`
`B.
`
`Ophthalmic Diseases that Cause Vision Loss and Blindness
`
`i.
`
`Wet Age-Related Macular Degeneration
`
`31. Wet Age-Related Macular Degeneration (“wet AMD”) is the most severe form of
`
`
`6
`The factual allegations in this Complaint are made based upon Regeneron’s first-hand knowledge
`with the exception of allegations made upon information and belief regarding Defendants’ conduct.
`
`
`
`11
`
`Novartis Exhibit 2057.011
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 12 of 92
`
`
`
`an eye disease that is the leading cause of blindness among older Americans.
`
`32.
`
`An estimated 11 million Americans suffer from some form of AMD, which erodes
`
`central vision. AMD has two forms: wet and dry. While dry AMD leads to a gradual loss of vision,
`
`wet AMD leads to faster vision loss and is the most advanced form of the disease. It is responsible
`
`for 90 percent of all AMD-related blindness.
`
`33. Wet AMD patients see the world as if through distorted lenses: straight lines may
`
`appear bent, central vision may be reduced, colors may be dulled, and patients may see haziness.
`
`Patients may also experience a well-defined blurry or blind spot in their central field of vision:7
`
`
`
`34.
`
`Day-to-day activities, such as reading, writing, driving, or even recognizing faces,
`
`are difficult for patients with wet AMD. The debilitating effects of wet AMD worsen over time
`
`and can be irreversible. If left untreated, wet AMD may cause permanent blindness.
`
`35. Wet AMD is caused by an overproduction of a naturally occurring VEGF protein
`
`in the body. VEGF’s normal role is to trigger formation of new blood vessels supporting the growth
`
`of the human body’s tissues and organs. When cells secrete too much VEGF into the eye, however,
`
`abnormal blood vessels grow underneath the macula and retina. These abnormal blood vessels can
`
`leak blood or fluid, blurring central vision and potentially causing blindness.
`
`
`7
`National Institutes of Health, https://www.nih.gov/health-information/nih-clinical-research-trials-
`you/age-related-macular-degeneration-amd (last visited July 13, 2020).
`
`
`
`12
`
`Novartis Exhibit 2057.012
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 13 of 92
`
`
`
`ii.
`Diabetic Retinopathy and Diabetic Macular Edema
`Diabetes is the leading cause of new cases of blindness in people 20 to 74 years of
`
`36.
`
`age in the United States.
`
`37.
`
`Diabetic Retinopathy (“DR”) is the most common diabetic eye disease and can lead
`
`to vision loss. DR occurs when too much blood sugar damages the blood vessels in the retina. As
`
`a result, the retina does not receive enough oxygen and nutrients, and blood vessels can leak blood
`
`and fluid into the retina.
`
`38.
`
`If DR progresses into its most advanced stage, an increased growth of new blood
`
`vessels occurs. These new blood vessels are fragile and easily damaged, which adds to the swelling
`
`and leaking in the retina.
`
`39.
`
`Diabetic Macular Edema (“DME”) is a complication of DR that can lead to further
`
`vision problems. DME occurs if the macula, the area of the retina at the back of the eye responsible
`
`for sharp central vision, swells with fluid leaked from those damaged blood vessels. DME can
`
`degrade the patient’s vision and, if left untreated, can cause blindness.
`
`iii. Macular Edema following Retinal Vein Occlusion
`Retinal Vein Occlusion (“RVO”) occurs when a blood vessel in the retina becomes
`
`40.
`
`blocked, often by a blood clot.
`
`41. When fluid leaks into the macula as a result of the blocked blood vessel, it is called
`
`Macular Edema following Retinal Vein Occlusion (“MEfRVO”). Vision loss or blurring occurs
`
`as the macula swells with the fluid.
`
`C.
`
`42.
`
`FDA-Approved Anti-VEGF Drugs
`
`There are several anti-VEGFs approved by the U.S. Food and Drug Administration
`
`(“FDA”) to treat certain ophthalmic diseases in the United States. The two primary approved drug
`
`treatments include EYLEA and LUCENTIS. Recently, FDA approved another anti-VEGF drug
`
`
`
`13
`
`Novartis Exhibit 2057.013
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 14 of 92
`
`
`
`product for the treatment of wet AMD, BEOVU® (brolucizumab-dbll) injection. BEOVU is also
`
`marketed by Defendant Novartis, but it has resulted in a host of severe safety issues for patients.
`
`i.
`
`LUCENTIS
`
`43.
`
`LUCENTIS is the brand name for the anti-VEGF (ranibizumab injection) co-
`
`developed by Defendant Novartis and Genentech, a wholly-owned subsidiary of Roche. Novartis
`
`paid Genentech/Roche an initial milestone fee and shared the cost for the subsequent development
`
`by making additional milestone payments upon the achievement of certain clinical development
`
`points and product approval. Novartis also markets and pays royalties on the net sales of
`
`LUCENTIS outside of the United States.8
`
`44.
`
`FDA first approved LUCENTIS in vial form in the United States in June 2006.
`
`FDA approved LUCENTIS in a PFS in October 2016, and it launched shortly thereafter in early
`
`2017. At this time nearly all LUCENTIS is sold in PFS in the United States.
`
`45.
`
`LUCENTIS is currently indicated for the treatment of patients with certain
`
`ophthalmic diseases, including wet AMD, DR, DME, and MEfRVO. LUCENTIS is recommended
`
`for intravitreal injection once a month.
`
`46.
`
`LUCENTIS is a multi-billion dollar franchise globally. LUCENTIS sales in the
`
`United States in 2018 amounted to approximately $1.6 billion9 while LUCENTIS sales in Europe
`
`
`8
`Form 20-F 2009, Novartis AG, “United States Securities and Exchange Commission Form 20-F
`2009” (Jan. 26, 2010), available at https://www.novartis.com/sites/www.novartis.com/files/Novartis-20-F-
`2009.pdf.
`
`9
`2018”
`Report
`“Finance
`Roche,
`2018,
`Report
`Finance
`at
`available
`https://www.roche.com/dam/jcr:933329c4-4564-4b17-a29b-246ac7e617d5/en/fb18e.pdf (last visited July
`13, 2020).
`
`
`
`14
`
`Novartis Exhibit 2057.014
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 15 of 92
`
`
`
`and the rest of the world in 2018 amounted to $2 billion.10
`
`47.
`
`Under the terms of their commercial agreement, Genentech has marketing rights
`
`for LUCENTIS in North America (United States, Canada, and Mexico) while Novartis has
`
`exclusive commercialization rights to sell LUCENTIS in Europe and the rest of the world.11
`
`48.
`
`Novartis has multiple economic interests in the LUCENTIS franchise. Novartis not
`
`only has 100% of the commercial rights for LUCENTIS outside of North America, but it also owns
`
`a 33.3% stake in Roche—the parent company of Genentech that sells LUCENTIS PFS in the
`
`United States. Novartis has had an ownership in Roche dating back to 2001.12 Indeed, Novartis’s
`
`current 33.3% stake in Roche is worth approximately $12.9 billion.13 Novartis has received
`
`dividend payments from Roche in excess of CHF 4 billion (approximately $4.3 billion USD) since
`
`2001.14 Novartis accordingly benefits from LUCENTIS’ sales outside of the U.S. as well as
`
`LUCENTIS’ U.S. sales through its 33.3% ownership stake in Roche.
`
`49.
`
`In addition, Novartis licensed its ’631 Patent to Genentech for LUCENTIS PFS in
`
`the United States.15 According to Novartis, the “LUCENTIS PFS uses Novartis’s PFS technology
`
`
`10
`Form 20-F 2018, Novartis AG, “United States Securities and Exchange Commission Form 20-F
`2018” (Jan. 30, 2019), available at https://www.novartis.com/sites/www.novartis.com/files/novartis-20-f-
`2018.pdf.
`
`11
`Press Release, Genentech, “Genentech and Novartis Ophthalmics Announce Development and
`Commercialization Agreement for Age-Related Macular Degeneration Treatment, Lucentis” (June 24,
`2003), available at https://www.gene.com/media/press-releases/6327/2003-06-24/genentech-and-novartis-
`ophthalmics-annou.
`
`12
`Investors, Frequently Asked Questions, Major Shareholders, available at
`Roche,
`https://www.roche.com/investors/faq_investors/major_shareholders.htm (last visited July 13, 2020).
`
`13
`Report,
`Annual
`2018
`Novartis,
`available
`https://www.novartis.com/sites/www.novartis.com/files/novartis-annual-report-2018-en.pdf.
`
`at
`
`14
`Novartis Delays Sale of Roche Stake, SeeNews Switzerland (Oct. 24, 2016), available at
`https://advance.lexis.com/api/permalink/8b30d1d6-ccfd-4f0d-bed0-1c5bd7708fee/?context=1000516.
`
`See Certain Pre-Filled Syringes for Intravitreal Injection and Components Thereof, DN 3460,
`15
`
`15
`
`
`
`Novartis Exhibit 2057.015
`Regeneron v. Novartis, IPR2020-01317
`
`

`

`Case 1:20-cv-05502-AJN Document 1 Filed 07/17/20 Page 16 of 92
`
`
`
`including the inventions recited in the ’631 patent. Genentech’s commercialization of the
`
`LUCENTIS PFS in the United States is pursuant to a license to that technology, including the ’631
`
`[P]atent.”16
`
`ii.
`
`EYLEA
`
`50.
`
`EYLEA (aflibercept) is a novel and groundbreaking anti-VEGF developed by
`
`Regeneron. EYLEA is an entirely different biologic than LUCENTIS. EYLEA is currently
`
`indicated for the treatment of patients with the following ophthalmic diseases: wet AMD, DR,
`
`DME, and MEfRVO.
`
`51.
`
`Regeneron’s EYLEA provides substantial benefits to patients compared to
`
`LUCENTIS because it requires less frequent injections. EYLEA is recommended for intravitreal
`
`injection once a month for the first three months, but then—unlike LUCENTIS—EYLEA can be
`
`injected once every two months