Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 1 of 39
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF MASSACHUSETTS
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`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBH
`and TEVA
`PHARMACEUTICALS USA,
`INC.,
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`Plaintiffs,
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`v.
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`ELI LILLY AND COMPANY,
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`Defendant.
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`Civil Action No. _______________
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`COMPLAINT FOR PATENT INFRINGEMENT
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`Plaintiffs Teva Pharmaceuticals International GmbH (“Teva GmbH”) and Teva
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`Pharmaceuticals USA, Inc. (“Teva USA”) (collectively, “Plaintiffs” or “Teva”) bring this
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`action for patent infringement and declaratory judgment against Defendant Eli Lilly and
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`Company (“Eli Lilly”).
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`NATURE OF THE ACTION
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`1.
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`Teva brings this action to protect its intellectual property rights covering
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`breakthrough treatments for migraine headaches. Teva has invested heavily in this innovative
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`technology, and the potential benefit to the public is enormous. Over 1 billion people suffer
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`from migraine headaches worldwide. More than 38 million people experience migraine
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`headaches in the United States alone.
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`2.
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`Migraine is a complex, common neurological condition that is characterized by
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`severe, episodic attacks of headache. Migraine can also cause nausea, vomiting, and sensitivity
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`to light, sound, or movement. In the United States and Western Europe, over 10% of the general
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`population suffers from migraine.
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 2 of 39
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`3.
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`Teva’s corporate affiliate, Labrys Biologics, Inc. (“Labrys”), made a major
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`breakthrough in research for migraine treatment. Through years of painstaking study, Labrys
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`made important discoveries concerning the role that calcitonin gene-related peptide (“CGRP”)
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`plays in migraine headaches. Armed with that knowledge, Labrys developed a biologic product
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`with an active ingredient, fremanezumab—a humanized monoclonal antibody that targets
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`CGRP. This new product has been shown to prevent and/or reduce the incidence of migraines.
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`Fremanezumab has the potential to help tens of millions of migraine sufferers in the United
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`States.
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`4.
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`Labrys’ innovations are protected by at least U.S. Patent Nos. 8,586,045;
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`8,597,649; 9,266,951; 9,340,614; 9,346,881; 9,884,907; 9,884,908; 9,890,210; and 9,890,211
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`(“the Patents-in-Suit”). Labrys assigned the Patents-in-Suit to Teva on September 19, 2016.
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`Teva, in turn, has continued to invest in fremanezumab to bring the product to market. On
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`October 16, 2017, Teva Branded Pharmaceutical Products R&D, Inc. submitted a Biologics
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`License Application (“BLA”) to the Food and Drug Administration (“FDA”) seeking
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`approval to market fremanezumab for the treatment of episodic and chronic migraine. On or
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`about March 22, 2018, Teva Branded Pharmaceuticals Products R&D, Inc. transferred the
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`BLA seeking approval to market fremanezumab for the treatment of episodic and chronic
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`migraine to Teva Pharmaceuticals USA, Inc. On September 19, 2018, Teva received FDA
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`approval to market fremanezumab in the United States under the brand name Ajovy™. See
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`Ex. 28. Teva Pharmaceuticals USA, Inc. is the exclusive distributor of Ajovy™ within the
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`United States.
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`5.
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`Eli Lilly is aware of the Patents-in-Suit, but nonetheless is, upon information and
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`belief, in the process of launching its own competing biologic product with the active ingredient
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`galcanezumab, which will undermine the value of Teva’s substantial investment in the Patents-
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 3 of 39
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`in-Suit. This product is also known as LY2951742 (the “Galcanezumab Product”). Like
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`Teva’s patented fremanezumab product, Eli Lilly’s infringing Galcanezumab Product is an
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`antibody that targets CGRP. On October 24, 2017, Eli Lilly publicly stated that it had
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`submitted its own BLA for the Galcanezumab Product. Ex. 1 at 3. Through its public
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`statements and commercial activity, Eli Lilly made clear that it intended to enter the market
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`with its Galcanezumab Product as soon as it received FDA approval.
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`6.
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`On September 27, 2018, Eli Lilly obtained FDA approval to market its
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`Galcanezumab Product in the United States under the brand name Emgality™. See Ex. 29. The
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`Eli Lilly press release describing the approval states that “Emgality will be available to patients
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`shortly after approval.” Id. This demonstrates that the commercial launch of Emgality™ is
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`imminent, and upon information and belief, Lilly is offering for sale, selling, manufacturing
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`and/or importing , Emgality™ into the United States.
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`7.
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`Eli Lilly’s commercial manufacture, importation, offers to sell, and sales of its
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`Galcanezumab Product will directly infringe, and/or actively induce and/or contribute to
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`infringement of, claims of each of the Patents-in-Suit. Teva files this action to recover damages
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`suffered as result of Lilly’s infringing conduct, to secure a judicial declaration that Eli Lilly has
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`infringed the Patents-in-Suit, and to prevent Eli Lilly from any future infringement.
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`THE PARTIES
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`8.
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`Teva GmbH is a limited liability company organized and existing under the
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`laws of Switzerland, having its corporate offices and principal place of business at
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`Schlüsselstrasse 12, Jona (SG) 8645, Switzerland. Teva GmbH owns the Patents-in-Suit.
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`9.
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`Teva USA is a Delaware corporation organized and existing under the laws of
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`Delaware, having its place of business at 1090 Horsham Road, North Wales, Pennsylvania
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`19454-1090. Teva USA holds an exclusive license to the Patents-in-Suit.
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 4 of 39
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`10.
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`Upon information and belief, Eli Lilly is a corporation organized and
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`existing under the laws of the State of Indiana. Eli Lilly has corporate offices at Corporate
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`Center, Indianapolis, Indiana 46285. Eli Lilly also has regular and established places of
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`business in other jurisdictions, including in the Commonwealth of Massachusetts.
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`JURISDICTION AND VENUE
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`11.
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`This Court has jurisdiction over the subject matter of this action pursuant to
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`28 U.S.C. §§ 1331 and 1338(a) and the Declaratory Judgment Act, 28 U.S.C. §§ 2201 and 2202.
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`12.
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`This Court has personal jurisdiction over Eli Lilly because Eli Lilly has
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`extensive contacts with the Commonwealth of Massachusetts that directly relate to this suit.
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`13.
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`Venue is proper in this Judicial District pursuant to 28 U.S.C. § 1391(b) because
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`Eli Lilly resides in this District. See 28 U.S.C. § 1391(c)(2). Venue is also proper in this
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`Judicial District pursuant to 28 U.S.C. § 1400(b) because Eli Lilly has a regular and established
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`place of business in Massachusetts and is committing (or will imminently commit) acts of
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`infringement in the Commonwealth based on the FDA approval and commercial launch of its
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`Galcanezumab Product.
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`A.
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`Eli Lilly Has Received FDA Approval, Allowing the Immediate Commercial
`Launch of its Galcanezumab Product.
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`14.
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`There is an actual controversy regarding Eli Lilly’s infringement of the Patents-
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`in-Suit by commercially manufacturing, offering to sell, and selling the Galcanezumab
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`Product. Eli Lilly engaged in extensive preparations to bring its Galcanezumab Product to
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`market in the immediate future, including submitting a BLA to the FDA for approval to market
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`and sell the Galcanezumab Product for the prevention of both episodic and chronic migraine.
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`15.
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`Over the course of the past year, Eli Lilly made many public statements
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`representing that it expected to receive FDA approval of its Galcanezumab Product and
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`indicating that it planned to commercially launch the Galcanezumab Product as soon as the
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 5 of 39
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`FDA approved its BLA.
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`16.
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`Eli Lilly has completed all of the Phase III clinical trials it believes are
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`necessary to support its application for FDA approval to market the Galcanezumab Product in
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`the United States. On October 24, 2017, Eli Lilly confirmed that it submitted a BLA with the
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`FDA to market and sell the Galcanezumab Product for the prevention of both episodic and
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`chronic migraine. This filing signaled a serious commitment by Eli Lilly to imminently launch
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`the Galcanezumab Product, because filing a BLA represents a substantial undertaking and
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`investment.
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`17.
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`Eli Lilly publicly expressed confidence that the FDA would approve its BLA in
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`2018. Eli Lilly made these statements in a special call with investors and at the Annual J.P.
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`Morgan Healthcare Conference. See Ex. 2 at 19-20; Ex. 3 at 19. Several of these statements
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`were made by C-level executives at Eli Lilly. In its June 28, 2017 Form 10-Q submitted to the
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`U.S. Securities and Exchange Commission, Eli Lilly identified the Galcanezumab Product as
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`being in Eli Lilly’s “late-stage pipeline.” Ex. 4 at 38.
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`18.
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`Eli Lilly publicly confirmed that it had incorporated the expected launch of its
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`Galcanezumab Product into its long-term revenue growth guidance for investors. For example,
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`during the question and answer portion of a July 25, 2017 Eli Lilly earnings call, Eli Lilly CFO
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`and Executive VP of Global Services, Derica Rice, responded to the question “[o]n
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`galcanezumab . . . is the launch reflected in your long-term revenue growth guidance?” by
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`saying “[y]es, the simple answer is yes.” Ex. 5 at 20, 21.
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`19.
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`Eli Lilly’s expectation that it would receive FDA approval to market the
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`Galcanezumab Product in the very near future was consistent with the FDA’s practice for
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`reviewing and approving BLAs. In 2016, the median total approval time for BLAs from the
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`date of filing was just 10.1 months. See Ex. 6 at 1. In fact, the FDA has established a goal of
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 6 of 39
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`acting on 90% of BLAs within 10 months of the 60-day filing date (the 60-day filing date is the
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`window of time in which the FDA decides whether to accept an application for substantive
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`review). See Ex. 7 at 4.
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`20.
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`On September 21, 2018, Eli Lilly issued a press release announcing that “the
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`European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use
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`(CHMP) has issued a positive opinion for Emgality™ (galcanezumab) for the prophylaxis of
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`migraine in adults who have at least four migraine days per month.” Ex. 36 at 1. Eli Lilly
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`characterized this result as “the first regulatory step toward approval for Emgality in Europe.”
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`Id. This press release also addressed the FDA approval process for Emgality™ in the United
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`States and stated that “a decision regarding approval is expected by the end of September
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`2018.” Id.
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`21.
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`Eli Lilly’s efforts culminated in the announcement on September 27, 2018 that
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`FDA had approved Eli Lilly’s BLA, clearing the way for the commercial launch of the
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`Galcanezumab Product in the United States. See Ex. 29.
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`B.
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`22.
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`Commercial Sales of The Galcanezumab Product Are Imminent.
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`Even before receiving FDA approval, Eli Lilly engaged in extensive
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`preparations to allow for an immediate commercial launch of its Galcanezumab Product
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`following FDA approval. For example, Eli Lilly instituted substantial marketing efforts
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`directed at healthcare providers to raise awareness of migraine treatment, developed education
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`materials about migraine, and built a sales force to launch the Galcanezumab Product. These
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`activities are generally undertaken by a pharmaceutical company when a product’s launch is
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`imminent. Eli Lilly engaged in these efforts in the United States generally and in
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`Massachusetts specifically.
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`23.
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`Eli Lilly invested heavily in developing an online presence directed to healthcare
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 7 of 39
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`providers, in the United States and Massachusetts, to promote migraine treatments and CGRP’s
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`role in migraine. For example, Eli Lilly established a Twitter account named
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`@LillyMigraine in June 2017. See Ex. 8 at 1 (“Lilly Migraine U.S. @LillyMigraine,”
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`TWITTER, https://twitter.com/lillymigraine (last visited Oct. 24, 2017)).
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`24.
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`As early as October 2017, Eli Lilly was building a sales force to support the
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`launch of its Galcanezumab Product, including in Massachusetts specifically. Eli Lilly’s job
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`board listed open positions for twenty-five sales representative positions who would be
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`assigned to market the Galcanezumab Product once it is approved by the FDA. At least one
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`of those positions was in Massachusetts. For example, Eli Lilly advertised a “Sales
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`Representative—Neuroscience” position for “Boston, Massachusetts.” Eli Lilly’s job board
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`stated that “[u]pon the anticipated approval of Galca [i.e., the Galcanezumab Product], this
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`position will primarily focus on the successful launch of Galca.” See Ex. 10 at 2.
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`25.
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`On June 27, 2018, Eli Lilly announced that the FDA conditionally accepted a
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`brand name for its Galcanezumab Product—Emgality™. Ex. 30 at 1. Eli Lilly has filed
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`trademark applications with the U.S. Patent and Trademark Office to protect the Emgality™
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`name and logo, and received Notices of Allowance for these marks on June 6, 2017, and
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`October 17, 2017, respectively. Ex. 31.
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`C.
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`26.
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`Eli Lilly Knows Its Galcanezumab Product Infringes The Patents-in-Suit.
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`Eli Lilly tracks and follows Teva’s patents related to the treatment of migraine
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`as it relates to CGRP. For that reason, Teva is informed and believes that Eli Lilly knows about
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`the Patents-in-Suit and the barrier that they pose to commercially launching the Galcanezumab
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`Product in the United States.
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`27.
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`On July 16, 2014, Eli Lilly initiated an opposition to European Patent No.
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`1957106 B1, titled “Antagonist antibodies directed against calcitonin gene-related peptide and
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 8 of 39
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`methods using the same” (“EP 1957106”). Ex. 11. Eli Lilly knows that EP 1957106 has
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`important implications for its Galcanezumab Product. The background section of Eli Lilly’s
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`opposition filing describes the role of CGRP in migraine and the history and shortcomings of
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`small molecule (i.e., non-biologic) treatments for migraine. Id. at 4-5. The opposition also
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`notes Eli Lilly’s belief that EP 1957106 “provide[s] a very broad scope of protection” that
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`“encompasses almost all anti-CGRP antagonist antibodies that may have therapeutic utility.”
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`Id. at 9.
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`28.
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`Eli Lilly also knows that there are United States patents in the same family as EP
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`1957106, including the Patents-in-Suit. EP 1957106 claims a related invention to the Patents-
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`in-Suit, and Eli Lilly noted in its opposition papers that EP 1957106 claims priority to
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`provisional U.S. Application No. 60/736,623 (“the ʼ623 application”). Ex. 11 at 2. All of the
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`Patents-in-Suit also claim priority to the ʼ623 application, and several of the applications that
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`issued as the Patents-in-Suit had already been published by the United States Patent Office
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`before Eli Lilly submitted its opposition to EP 1957106. All of the applications that issued as
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`the Patents-in-Suit were published by the end of 2015, before Eli Lilly submitted additional
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`opposition papers throughout 2016 that continued to reference the ʼ623 application. Ex. 12 at
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`9- 10; Ex. 11 at 11. In February 2017, the European Patent Office found that EP 1957106 is
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`entitled to the priority date of the ʼ623 application. Ex. 13 at Sheet 9-11.
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`29.
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`Upon information and belief, Eli Lilly pressed ahead with its BLA filing even
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`though it knows that its Galcanezumab Product infringes the Patents-in-Suit. During a June 19,
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`2017, “special call” with investors, Eli Lilly Global Brand Development Leader for Migraine,
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`Robert Conley, responded to a question asking whether Eli Lilly “intend[s] to file” for approval
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`of its Galcanezumab Product “in Europe given the patent issues” and whether he thought “those
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`patent issues are relevant in the U.S.” by stating that, considering “the specifics of this case,”
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 9 of 39
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`Eli Lilly “certainly [is] planning . . . on FDA submission.” See Ex. 14 at 10-11.
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`30.
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`Eli Lilly also continued to pursue approval of its BLA even after Teva filed
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`actions seeking declaratory relief that Eli Lilly’s planned commercial launch of the
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`Galcanezumab Product would infringe the Patents-in-Suit.
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`31.
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`Eli Lilly has already created a case and controversy regarding the validity of
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`six of the nine patents-in-suit by initiating Inter Partes Review (“IPR”) proceedings against
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`these patents before the Patent Trial and Appeal Board (“PTAB”). Because, as described
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`above, Eli Lilly knows its Galcanezumab Product will infringe these patents, these IPR filings
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`demonstrate that commercial launch of the Galcanezumab Product is imminent.
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`32. On August 8, 2018, Eli Lilly filed six individual IPR petitions alleging that
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`U.S. Patent Nos. 8,597,649, 9,266,951, 9,340,614, 9,266,951, 9,346,881, 9,890,210,
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`9,890,211, are each invalid as obvious. The IPR docket numbers corresponding to Eli Lilly’s
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`filings against each of these Patents-in-Suit are, respectively, IPR2018-01427, IPR2018-
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`01423, IPR2018-01422, IPR2018-01424, IPR2018-01425, and IPR2018-01426. As described
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`in detail below, Teva asserts that Eli Lilly’s Galcanezumab Product infringes each of these six
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`Patents-in-Suit.
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`D.
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`Eli Lilly Has A Substantial And Continuous Presence In This Judicial
`District And Intends To Commit Acts Of Infringement In
`Massachusetts.
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`33.
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`Eli Lilly has extensive contacts with the Commonwealth of Massachusetts and
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`is actively engaged in the business of marketing and selling pharmaceutical products in
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`Massachusetts. Moreover, this suit is directly related to Eli Lilly’s contacts with
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`Massachusetts.
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`1.
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`Eli Lilly Has A Long History Connecting
`Its Business To Massachusetts.
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`34.
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`Eli Lilly is registered to do business in the Commonwealth of Massachusetts
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 10 of 39
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`and has designated National Registered Agents, Inc., 155 Federal Street, Suite 700, Boston,
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`MA 02110 as its registered agent for service of process in Massachusetts. See Ex. 15 at 1.
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`35.
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`Eli Lilly filed a Foreign Corporation Certificate of Registration in the
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`Commonwealth of Massachusetts. As a registered Foreign Corporation, Eli Lilly is required
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`to file Annual Reports with the Commonwealth.
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`36.
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`In its January 24, 2017 Annual Report filed with Massachusetts, Eli Lilly
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`described its business in the Commonwealth as “pharmaceutical manufacturing and sales.”
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`See Ex. 15 at 2.
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`37.
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`Eli Lilly has dozens of pharmaceutical drug products that it currently
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`markets, sells, and distributes in Massachusetts. See Ex. 16 (“Products,” ELI LILLY AND
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`COMPANY, https://www.lilly.com/products (last visited September 27, 2018)).
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`38.
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`Eli Lilly also employs consultants and sales people in Massachusetts to work
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`with Massachusetts healthcare providers.
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`2.
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`Eli Lilly Has A Regular And Established
`Place Of Business In Massachusetts.
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`39.
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`As of October 24, 2017, Eli Lilly’s public website lists the following address
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`as one of its “U.S. Locations:”
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`Cambridge, MA
`Eli Lilly and Company 450 Kendall Street
`Cambridge, MA 02142
`+1-617-225-3226
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`See Ex. 17 at 1.
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`40.
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`The Cambridge, Massachusetts address is home to Eli Lilly’s “Cambridge
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`Innovation Center” (“Innovation Center”). The Innovation Center serves as a location for the
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`company’s research and development efforts with respect to drug delivery and device
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`innovation. This Innovation Center includes research into treatments for pain and biologics
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 11 of 39
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`that require injections.
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`41.
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`In a May 6, 2015 video discussing the Innovation Center, Eli Lilly Vice
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`President of Delivery and Device Research, Divakar Rmakrishnan, explained that the
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`Innovation Center was created to employ “a subset of [Eli Lilly’s] R&D Group.” See Ex. 18
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`(Introducing Lilly’s Cambridge Innovation Center Video, at 0:00 to 0:18, ELI LILLY AND
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`COMPANY, May 6, 2015, available at https://careers.lilly.com/Cambridge-Innovation-Center).
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`42.
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`On May 6, 2015, Eli Lilly issued a press release concerning the Innovation
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`Center. Eli Lilly’s then Chairman, President, and CEO John Lechleiter made numerous
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`public statements about the Innovation Center. Ex. 19.
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`43. Mr. Lechleiter stated that Eli Lilly planned to employ “about 30 scientists and
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`engineers” at the Innovation Center, which would increase Eli Lilly’s “delivery and device
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`research and development space by nearly 50 percent, while increasing its staff by 25
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`percent.” See id. at 1.
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`44. Mr. Lechleiter announced in that press conference that “[n]ew drug delivery
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`and device innovation is critically important to Lilly’s growing portfolio of potential
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`medicines, particularly in our focus areas,” which includes treatments for “pain.” Id. The
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`press release added that “[m]ore than half of the company’s pipeline now comprises biologics
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`that require some type of injection” and that “[t]he company expects its revenues from
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`device-enabled products to double by 2020.” Id.
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`45.
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`The Galcanezumab Product is a biologic product that is administered by
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`injection and, upon information and belief, is part of the Innovation Center’s mandate.
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`THE PATENTS-IN-SUIT
`U.S. Patent No. 8,586,045
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`On November 19, 2013, United States Patent No. 8,586,045 (“the ’045 patent”),
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`A.
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`46.
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 12 of 39
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`titled “Methods of Using Anti-CGRP Antagonist Antibodies,” issued to Labrys Biologics, Inc.
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`as assignee of the named inventors Joerg Zeller, Kristian T. Poulsen, Yasmina N. Abdiche,
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`Jaume Pons, Sierra Leigh Jones Collier, and Arnon Rosenthal. A copy of the ’045 patent is
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`attached as Exhibit 20.
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`47.
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`On July 21, 2014, Labrys Biologics, Inc. was acquired by Teva
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`Pharmaceuticals USA, Inc. A confirmatory assignment of the ’045 patent from Labrys to
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`Teva Pharmaceuticals International GmbH was executed on September 19, 2016. The ’045
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`patent is valid and enforceable.
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`48.
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`The claims of the ’045 patent are directed to methods for reducing incidence of
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`or treating at least one vasomotor symptom including, for example, headache in an individual.
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`These methods comprise administering to the individual an effective amount of a human or
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`humanized anti-CGRP antagonist antibody.
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`49.
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`An anti-CGRP antagonist antibody is able to bind to CGRP and inhibit CGRP
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`biological activity and/or downstream pathway(s) mediated by CGRP signaling.
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`50.
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`B.
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`51.
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`The ’045 patent states that vasomotor symptoms include migraine.
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`U.S. Patent No. 8,597,649
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`On December 3, 2013, United States Patent No. 8,597,649 (“the ’649 patent”),
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`titled “Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide and Methods
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`Using Same,” issued to Labrys Biologics, Inc. as assignee of the named inventors Joerg Zeller,
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`Kristian T. Poulsen, Yasmina N. Abdiche, Jaume Pons, Sierra Leigh Jones Collier, and Arnon
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`Rosenthal. A copy of the ’649 patent is attached as Exhibit 21.
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`52.
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`A confirmatory assignment of the ’649 patent from Labrys to Teva was executed
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`on September 19, 2016. The ’649 patent is valid and enforceable.
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`53.
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`The claims of the ’649 patent are directed to an isolated human or humanized
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 13 of 39
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`anti-CGRP antagonist antibody with a binding affinity (KD) to human α-CGRP of 50 nM or less
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`as measured by surface plasmon resonance at 37º C.
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`C.
`
`54.
`
`U.S. Patent No. 9,266,951
`
`On February 23, 2016, United States Patent No. 9,266,951 (“the ’951 patent”),
`
`titled “Antagonist antibodies directed against calcitonin gene-related peptide and methods using
`
`same,” issued to Labrys Biologics, Inc. as assignee of the named inventors Joerg Zeller,
`
`Kristian T. Poulsen, Yasmina N. Abdiche, Jaume Pons, Sierra Leigh Jones Collier, and Arnon
`
`Rosenthal. A copy of the ’951 patent is attached as Exhibit 22.
`
`55.
`
`A confirmatory assignment of the ’951 patent from Labrys to Teva was executed
`
`on September 19, 2016. The ’951 patent is valid and enforceable.
`
`56.
`
`The claims of the ’951 patent are directed to a human or humanized monoclonal
`
`anti-CGRP antagonist antibody that binds human α-CGRP and inhibits cyclic adenosine
`
`monophosphate (cAMP) activation in cells.
`
`D.
`
`57.
`
`U.S Patent No. 9,340,614
`
`On May 17, 2016, United States Patent No. 9,340,614 (“the ’614 patent”), titled
`
`“Antagonist antibodies directed against calcitonin gene-related peptide and methods using
`
`same,” issued to Labrys Biologics, Inc. as assignee of the named inventors Joerg Zeller,
`
`Kristian T. Poulsen, Yasmina N. Abdiche, Jaume Pons, Sierra Leigh Jones Collier, and Arnon
`
`Rosenthal. A copy of the ’614 patent is attached as Exhibit 23.
`
`58.
`
`A confirmatory assignment of the ’614 patent from Labrys to Teva was executed
`
`on September 19, 2016. The ’614 patent is valid and enforceable.
`
`59.
`
`The claims of the ’614 patent are directed to a human or humanized, monoclonal
`
`anti-CGRP antagonist antibody that preferentially binds to human α-CGRP as compared to
`
`amylin.
`
`13
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 14 of 39
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`
`
`E.
`
`60.
`
`U.S Patent No. 9,346,881
`
`On May 24, 2016, United States Patent No. 9,346,881 (“the ’881 patent”), titled
`
`“Antagonist antibodies directed against calcitonin gene-related peptide and methods using
`
`same,” issued to Labrys Biologics, Inc. as assignee of the named inventors Joerg Zeller,
`
`Kristian T. Poulsen, Yasmina N. Abdiche, Jaume Pons, Sierra Leigh Jones Collier, and Arnon
`
`Rosenthal. A copy of the ’881 patent is attached as Exhibit 24.
`
`61.
`
`A confirmatory assignment of the ’881 patent from Labrys to Teva was executed
`
`on September 19, 2016. The ʼ881 patent is valid and enforceable.
`
`62.
`
`The claims of the ’881 patent are directed to a human or humanized, monoclonal
`
`anti-CGRP antagonist antibody that binds human α-CGRP and inhibits human α-CGRP from
`
`binding to its receptor as measured by a radioligand binding assay in SK-N-MC cells.
`
`
`F.
`
`U.S. Patent No. 9,884,907
`
`63.
`
`On February 6, 2018, United States Patent No. 9,884,907 (“the ’907 patent”),
`
`titled “Methods for treating headache using antagonist antibodies directed against calcitonin
`
`gene-related peptide,” issued to Teva Pharmaceuticals International GmbH as assignee of the
`
`named inventors Joerg Zeller, Kristian T. Poulsen, Yasmina Noubia Abdiche, Jaume Pons,
`
`Sierra Jones Collier, and Arnon Rosenthal. A copy of the ’907 patent is attached as Exhibit
`
`32.
`
`64.
`
`65.
`
`The ’907 patent is valid and enforceable.
`
`The claims of the ’907 patent are directed to a method of treating headache in an
`
`individual, comprising administering to the individual an effective amount of a humanized
`
`monoclonal anti-CGRP antagonist antibody, comprising: two human IgG heavy chains, each
`
`heavy chain comprising three complementarity determining regions (CDRs) and four
`14
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`
`
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`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 15 of 39
`
`framework regions, wherein portions of the two heavy chains together form an Fc region; and
`
`two light chains, each light chain comprising three CDRs and four framework regions; wherein
`
`the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues
`
`1 to 37 of SEQ ID NO:15 or SEQ ID NO:43.
`
`66.
`
`67.
`
`The ’907 patent discloses that headache includes migraine.
`
`The ’907 patent discloses that SEQ ID NO:15 recites the amino acid sequence of
`
`human α-CGRP and SEQ ID NO:43 recites the amino acid sequence of human β-CGRP.
`
`G.
`
`68.
`
`U.S. Patent No. 9,884,908
`
`On February 6, 2018, United States Patent No. 9,884,908 (“the ’908 patent”),
`
`titled “Antagonist antibodies directed against calcitonin gene-related peptide and methods using
`
`same,” issued to Teva Pharmaceuticals International GmbH as assignee of the named inventors
`
`Joerg Zeller, Kristian T. Poulsen, Yasmina Noubia Abdiche, Jaume Pons, Sierra Jones Collier,
`
`and Arnon Rosenthal. A copy of the ’908 patent is attached as Exhibit 33.
`
`69.
`
`70.
`
`The ’908 patent is valid and enforceable.
`
`The claims of the ’908 patent are directed to a method of treating headache in an
`
`individual, comprising: administering to the individual an effective amount of a humanized
`
`monoclonal anti-CGRP antagonist antibody, comprising: two human IgG heavy chains, each
`
`heavy chain comprising three CDRs and four framework regions, wherein portions of the two
`
`heavy chains together form an Fc region; and two light chains, each light chain comprising
`
`three CDRs and four framework regions; wherein the CDRs impart to the antibody specific
`
`binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID
`
`NO:43, and wherein the antibody binds to the CGRP with a binding affinity (KD) of about 10
`
`nM or less as measured by surface plasmon resonance at 37º C.
`
`71.
`
`The ’908 patent discloses that headache includes migraine.
`
`15
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`

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`
`
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`
`
`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 16 of 39
`
`72.
`
`The ’908 patent discloses that SEQ ID NO:15 recites the amino acid sequence of
`
`human α-CGRP and SEQ ID NO:43 recites the amino acid sequence of human β-CGRP.
`
`H.
`
`73.
`
`U.S. Patent No. 9,890,210
`
`On February 13, 2018, United States Patent No. 9,890,210 (“the ’210 patent”),
`
`titled “Antagonist antibodies directed against calcitonin gene-related peptide,” issued to Teva
`
`Pharmaceuticals International GmbH as assignee of the named inventors Joerg Zeller, Kristian
`
`T. Poulsen, Yasmina Noubia Abdiche, Jaume Pons, Sierra Jones Collier, and Arnon
`
`Rosenthal. A copy of the ’210 patent is attached as Exhibit 34.
`
`74.
`
`75.
`
`The ’210 patent is valid and enforceable.
`
`The claims of the ’210 patent are directed to a humanized monoclonal anti-
`
`CGRP antagonist antibody, comprising: two human IgG heavy chains, each heavy chain
`
`comprising three CDRs and four framework regions, wherein portions of the two heavy chains
`
`together form an Fc region; and two light chains, each light chain comprising three CDRs and
`
`four framework regions; wherein the CDRs impart to the antibody specific binding to a CGRP
`
`consisting of amino acid residues 1 to 37 of SEQ ID NO: 15 or SEQ ID NO: 43.
`
`76.
`
`The ’210 patent discloses that SEQ ID NO:15 recites the amino acid sequence of
`
`human α-CGRP and SEQ ID NO:43 recites the amino acid sequence of human β-CGRP.
`
`I.
`
`77.
`
`U.S. Patent No. 9,890,211
`
`On February 13, 2018, United States Patent No. 9,890,211 (“the ’211 patent”),
`
`titled “Antagonist antibodies directed against calcitonin gene-related peptide,” issued to Teva
`
`Pharmaceuticals International GmbH as assignee of the named inventors Joerg Zeller, Kristian
`
`T. Poulsen, Yasmina Noubia Abdiche, Jaume Pons, Sierra Jones Collier, and Arnon Rosenthal.
`
`A copy of the ’211 patent is attached as Exhibit 35.
`
`78.
`
`The ’211 patent is valid and enforceable.
`
`16
`
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`

`
`
`
`
`
`
`Case 1:18-cv-12029-ADB Document 1 Filed 09/27/18 Page 17 of 39
`
`79.
`
`The claims of the ’211 patent are directed to a humanized monoclonal anti-
`
`CGRP antagonist antibody, comprising: two human IgG heavy chains, each heavy chain
`
`comprising three CDRs and four framework regions, wherein portions of the two heavy chains
`
`together form an Fc region; and two light chains, each light chain comprising three CDRs and
`
`four framework regions; wherein the CDRs impart to the antibody specific binding to a CGRP
`
`consisting of amino acid residues 1 to 37 of SEQ ID NO: 15 or SEQ ID NO: 43, and wherein
`
`the antibody binds to the CGRP with a binding affinity (KD) of about 10 nM or less as
`
`measured by surface plasmon resonance at 37°C.
`
`80.
`
`The ’211 patent discloses that SEQ ID NO:15 recites the amino acid sequence of
`
`human α-CGRP and SEQ ID NO:43 recites the amino acid sequence of human β-CGRP.
`
`DEFENDANT’S INFRINGING CONDUCT
`
`81.
`
`On October 24, 2017, Eli Lilly confirmed that it has submitted a BLA
`
`requesting approval of its Galcanezumab Product for the prevention of both episodic and
`
`chronic migraine