Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 1 of 53
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`UNITED STATES DISTRICT COURT
`DISTRICT OF MASSACHUSETTS
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`Civil Action No. 18-cv-12029-ADB
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`**********
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`Plaintiffs,
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`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBH and
`TEVA PHARMACEUTICALS
`USA, INC.,
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`v.
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`ELI LILLY AND COMPANY,
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`Defendant.
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`MEMORANDUM & ORDER ON CROSS-MOTIONS FOR SUMMARY JUDGMENT
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`Plaintiffs Teva Pharmaceuticals International GmbH and Teva Pharmaceuticals USA,
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`Inc. (collectively, “Teva”) and Defendant Eli Lilly and Company (“Lilly”), competing
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`pharmaceutical companies, have both developed antibodies capable of treating headache
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`disorders associated with calcitonin gene-related peptide (“CGRP”). In the instant case, Teva
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`alleges that Lilly has infringed three of its patents1 (the “Patents-in-Suit”), seeks a declaration
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`that Lilly is judicially estopped from raising arguments that conflict with arguments it made in
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`prior inter partes review (“IPR”) proceedings, and argues that Teva does not have unclean hands
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`or engage in inequitable conduct. Lilly, in turn, seeks declarations that its product, Emgality®,
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`also known as Galcanezumab, does not infringe the patents, willfully or otherwise, and that the
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`asserted patents are invalid under 35 U.S.C. § 112.
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`1 U.S. Patent Nos. 8,586,045 (the “’045 patent”); 9,884,907 (the “’907 patent”); and 9,884,908
`(the “’908 patent”).
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`Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 2 of 53
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`I.
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`FACTUAL BACKGROUND
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`After weeding through the more than 1,296 pages of asserted facts and responses, the
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`following facts are undisputed except where otherwise noted.
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`A. Migraine, Headache Disorders & CGRP
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` “Migraine is a common chronic, recurrent neurological disorder that affects greater than
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`10% of adults globally and approximately 39 million individuals in the United States.” [ECF
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`No. 400 ¶ 106 (citation omitted)].2 It is among the more than 200 classifications of headache
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`disorders listed by the International Classification of Headache Disorders, 2nd edition. [Id. ¶
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`110].
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`CGRP is a neuropeptide that, as of 2005–2006,3 was understood to be involved in head
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`pain in a variety of contexts, including migraine headaches. [ECF No. 400 ¶¶ 114, P47]. At that
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`time, CGRP had been the subject of thousands of peer-reviewed articles, [id. ¶ P46], and drugs
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`affecting the CGRP pathway were used to treat migraine and other forms of headaches, [id. ¶
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`P48]. CGRP has four functional regions: (1) the N-terminal end; (2) the mid-region; (3) a hinge-
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`like region; and (4) the C-terminal end. [Id. ¶ 113].
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`B.
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`Antibodies
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`An antibody, or immunoglobin, is a specialized protein molecule that recognizes and
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`binds to a target molecule known as an antigen. [ECF No. 400 ¶ 26]. “The main function of
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`2 The Court draws the facts primarily from the parties’ Reply Statements of Material Facts, [ECF
`Nos. 387 (Unclean Hands), 389 (Judicial Estoppel), 395 (Willful Infringement), 400 (Written
`Description), 406 (Non Infringement), and 411 (Lack of Enablement)], which contain both
`parties’ positions on the material facts, and the documents referenced therein. The Court further
`notes that citations to specific paragraphs are inclusive of the response to said paragraph.
`3 The Court looks to scientific knowledge as of 2005 to 2006 because the Patents-in-Suit claim
`priority to Provisional Application No. 60/736,623, which was filed on November 14, 2005, and
`to Application No. 12/093,638, which was filed on November 2, 2006. [ECF No. 411 ¶ 142].
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`2
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`Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 3 of 53
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`antibodies is to bind to antigens and neutralize them or to mark them for destruction.” [Id. ¶ 48].
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`The portion of an antigen that is bound by an antibody is called an epitope. [Id. ¶ 27].
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`Antibodies themselves are made up of amino acids that are connected to each other in linear
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`chains, often referred to as amino acid sequences. [Id. ¶ 29].
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`Typical full-length antibodies have four chains of amino acids: two identical heavy
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`chains and two identical light chains. [ECF No. 400 ¶¶ 30, 32]. Each heavy chain and each light
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`chain has a variable domain and each variable domain has three complementarity determining
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`regions (“CDRs”). [Id. ¶¶ 31–33]. Thus, a typical full-length antibody has six unique CDRs
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`and two unique variable domains. See [id. ¶¶ 32–33, 68, P35, P104]. The CDRs, which combine
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`to form the variable domains, form the primary binding interface between the antibody and the
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`epitope of the antigen, [id. ¶ 37], with the amino acid sequence of each of the CDRs causing the
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`variable domains to adopt unique three-dimensional structures, [ECF No. 406 ¶¶ 17–18]. The
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`amino acid sequence of the variable region differs for each antibody, [ECF No. 400 ¶ 34], and
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`contains approximately 220 amino acid residues, [id. ¶ 35].
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`The number of possible permutations of antibodies is extraordinarily broad. See [ECF
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`No. 400 ¶ 59]. The claims in the Patents-in-Suit, however, do not claim every antibody that
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`could possibly be generated, rather they claim “a specific subset of anti-CGRP antibodies that
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`antagonize CGRP function.” [Id. ¶ 66 (quoting ECF No. 296-64 ¶ 206)]. Lilly argues that this
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`subset of antibodies would nonetheless be extraordinarily hard to identify because “[a]s of 2005–
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`2006 it was not possible to predict an antibody’s function based on its amino acid sequence.”
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`[Id. ¶ 72]. Teva disputes this, arguing that, by that time, “it was well known that antibodies have
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`common amino acid sequences that contribute in known ways to known functions, including
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`antibodies generally and antibodies within particular known classes.” [Id.].
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`3
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`C.
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`Development of Antibodies for Therapeutics
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`To be safe and effective as a treatment for any type of headache disorder, an antibody
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`must share certain general characteristics with naturally occurring human antibodies. See [ECF
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`No. 400 ¶¶ 93–94]. If it does not, the antibody may be recognized by the body as foreign and
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`become the target of a potentially dangerous immune response, resulting in the elimination of the
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`antibody, a loss of therapeutic efficacy, and possibly serious allergic reactions. [Id. ¶ 93].
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`As of 2005–2006, one of the processes used to develop new therapeutic antibodies
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`involved the use of murine (i.e., mouse) antibodies. [ECF No. 400 ¶ 91]. These murine
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`antibodies were generated by injecting mice with an antigen of interest, which caused the mouse
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`to produce a type of white blood cell, referred to as B cells, that, in turn, produced a large variety
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`of antibodies to protect against what the mouse’s immune system perceived as a foreign antigen.
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`See [id. ¶¶ 91–92]. Scientists then could isolate a B cell, fuse it to a cancer cell to form a hybrid
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`cell known as a hybridoma, which then produced antibodies having an identical amino acid
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`sequence (i.e., “monoclonal” antibodies). [Id. ¶ 92]. An antibody produced in this way is not
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`human, however, and to avoid human immune systems rejecting the foreign antibody, it was
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`necessary to use genetic engineering to “humanize” the murine antibodies. [Id. ¶¶ 93–94]. This
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`process involved replacing portions of the genes encoding the murine antibody with portions that
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`encode a human antibody. [Id. ¶ 94]. As of 2005–2006, humanization of murine antibodies was
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`sufficiently established to be considered “conventional” and “routine,” but the parties dispute
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`how labor intensive and time consuming the process was. See [id. ¶¶ 95–98, P8, P54, P64–66].
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`D.
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`Key Antibody Attributes
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`To be effective in treating headache disorders caused by CGRP, an antibody produced by
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`the methods previously described must possess several characteristics. Among the most
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`important is its “affinity” for the target antigen, which refers to how strongly the antibody
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`4
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`attaches to the target. [ECF No. 400 ¶ 42]. One measure of affinity is the dissociation constant
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`of the antibody-antigen interaction, or “KD” value. See [id. ¶ 189]. A related property is an
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`antibody’s “neutralizing” capability, meaning its ability to inhibit the biological activities of the
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`antigen to which it binds. [Id.]. A high affinity is integral to an antibody’s neutralizing
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`capability, otherwise the antibody will not effectively inhibit the target antigen (e.g., CGRP).
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`See [id. ¶ P67].4
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`E.
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`The Asserted Patents and Specifications
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`Teva asserts twenty claims from three patents: the ’045, ’907, and ’908 patents. See
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`[ECF No. 400 ¶ 1; ECF No. 298 at 6]. The patents each claim the use of human or humanized
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`anti-CGRP antagonist antibodies5 to treat vasomotor symptoms, such as headaches. [ECF No.
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`400 ¶ 185–86]. The ’045 patent is titled “Methods of Using Anti-CGRP Antagonist Antibodies,”
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`and the ’907, and ’908 patents share the title “Methods for Treating Headache Using Antagonist
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`Antibodies Directed Against Calcitonin Gene-Related Peptide.” [ECF No. 387 ¶¶ 1, 3, 5].
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`Named inventors for all three patents include, among others, Joerg Zeller, Kristian T. Poulsen,
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`Yasmina Noubia Abdiche, and Jaume Pons. [Id. ¶¶ 2, 4, 6]. Each of the Patents-in-Suit claim
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`priority to Provisional Patent Application No. 60/736,623, which was filed on November 14,
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`2005, and to Application No. 12/093,638, which was filed on November 2, 2006, [ECF No. 400
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`¶ 183], and later published on May 18, 2007 as International Publication Number WO
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`2007/054809 (the “’809 application”), [ECF No. 395 ¶ P2].
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`4 Teva objects to Paragraph P67, [ECF No. 400 ¶ P67], but does not dispute that antibodies that
`bind to the C-terminal, mid-, or N-terminal regions of CGRP can all antagonize CGRP if they
`exhibit high enough binding affinity and block CGRP’s interaction with the CGRP receptor.
`5 The Court has construed the term “anti-CGRP antagonist antibody” as “an antibody that is able
`to bind to CGRP and inhibit CGRP biological activity and/or downstream pathway(s) mediated
`by CGRP signaling.” [ECF No. 101 at 11].
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`5
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`i.
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`The ’045 Patent
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`Teva asserts one independent claim from the ’045 patent, which recites as follows:
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`17. A method for reducing incidence of or treating headache in a human,
`comprising administering to the human an effective amount of anti-CGRP
`antagonist antibody, wherein said anti-CGRP antagonist antibody is a human
`monoclonal antibody or a humanized monoclonal antibody.
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`[ECF No. 400 ¶ 251]. The Court has previously construed the term “effective amount” to
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`mean “an amount sufficient to effect beneficial or desired results, including but not
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`limited to clinical results.” [ECF No. 101 at 31]. Teva also asserts seven dependent
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`claims of the ’045 patent, [ECF No. 400 ¶ 252]: claims 18 and 21 recite specific amino
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`acid sequences of portions of the antibodies, [id. ¶¶ 253, 256], claim 19 limits the
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`condition treated to several specific headache disorders, [id. ¶ 254], claim 20 specifies the
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`strength of binding, [id. ¶ 255], claim 24 limits the condition treated to migraine, [id. ¶
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`257], claim 27 limits the routes of administration, [id. ¶ 258], and claim 30 requires that
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`the anti-CGRP antagonist antibody is a humanized monoclonal antibody, [id. ¶ 259].
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`ii.
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`The ’907 and ’908 Patents
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`Teva similarly asserts one independent claim of the ’907 patent, claim 1, which recites as
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`follows:
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`1. A method for 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
`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.
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`[ECF No. 400 ¶ 262]. Teva has asserted five dependent claims from claim 1 of the ’907
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`patent: claim 4 requires that the antibody be administered intravenously or
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`6
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`subcutaneously, [id. ¶ 264], claim 5 limits the condition treated to one of a specific set of
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`headache disorders, [id. ¶ 265], claim 6 limits the condition treated to migraine, [id. ¶
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`266], and claim 15 specifies that the constant regions of the IgG heavy chains are IgG4
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`constant regions, [id. ¶ 267].
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`The asserted independent claim from the ’908 patent, claim 1, is identical to claim
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`1 of the ’907 patent, with the following information added to the end: “and wherein the
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`antibody binds to the CGRP with a binding affinity (KD) of about 10 nM or less as
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`measured by surface plasmon resonance at 37° C.” [ECF No. 400 ¶ 269]. Teva asserts
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`five dependent claims from the ’908 patent, which are identical in number and language
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`to the dependent claims asserted in the ’907 patent. [Id. ¶¶ 270–75].
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`iii.
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`The Shared Specification of the Patents-in-Suit
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`The specifications in each of the Patents-in-Suit are substantively identical, [ECF No. 400
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`¶ 184], and describe the claimed invention as “concern[ing] anti-CGRP antagonist antibodies and
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`methods of using anti-CGRP antagonist antibodies for treating or preventing . . . headaches, such
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`as migraine” as well as other types of headaches. [ECF No. 411 ¶ 144]. The specification (1)
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`states that” [a]nti-CGRP antagonist antibodies are known in the art . . . .” [ECF No. 400 ¶ 204
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`(Teva, in response, citing the ’045 patent at 25:59–61)];6 (2) describes a full-length humanized
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`“anti-CGRP antagonist antibody referred to as Antibody G1 and later re-named
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`fremanezumab[,]” [ECF No. 411 ¶ 145 (citations omitted)], as well as 84 humanized anti-CGRP
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`antibody variants of G1 (“M1-M84”), which vary from Antibody G1 by 10 or fewer amino acids,
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`6 Lilly agrees that murine anti-CGRP antibodies were known in the art but disputes that
`humanized or human anti-CGRP antibodies were known in the art. See, e.g., [ECF No. 400 ¶
`P28].
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`7
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`[ECF No. 400 ¶¶ 192, P103];7 (3) discloses the complete amino acid sequence of Antibody G1,
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`including the variable region and CDR portions of the antibody, [id. ¶ P104]; (4) discloses, in
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`addition to the humanized antibodies, 12 murine anti-CGRP antibodies, seven of which were
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`shown to be CGRP antagonists, [id. ¶ P102]; (5) describes “the routine methods for making
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`humanized and human antibodies[,]” [id. ¶ P97 (citation omitted)], but does not disclose how
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`Antibody G1, in particular, was made, [id. ¶ 188]; (6) states that by 2005–2006, methods for
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`humanization of antibodies were well-known, routine, and reliable in the prior art and that
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`conventional humanization techniques were routinely used that preserved the affinity and
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`specificity of the donor antibody, [id. ¶ P64–65]; (7) discloses that there were well-known
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`screening techniques, such as the cAMP activation assay, that allowed researchers to determine
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`whether an antibody antagonized CGRP,8 [id. ¶ P63]; (8) reports that Antibody G1 binds to the
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`C-terminal end of CGRP, [id. ¶ 190]; (9) includes data on antibodies that bind to CGRP’s C-
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`terminal but do not inhibit CGRP’s effects, [ECF No. 387 ¶ 22]; (10) provides instruction about
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`how to formulate antibodies, including anti-CGRP antagonist antibodies, and various modes of
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`administration, [ECF No. 400 ¶ P135]; (11) offers specific examples of formulations for
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`common modes of administration and cites prior art where further detail can be found, [id.];9
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`7 Light chain CDR3, heavy chain CDR1, and heavy chain CDR3 of all 84 variants (M1–M84)
`are identical to those of Antibody G1. [ECF No. 400 ¶ 194]. Additionally, the specification
`does not report in vitro or in vivo experiments evaluating the ability of antibodies M1–M84 to
`inhibit CGRP biological activity. [Id. ¶ 196]
`8 The parties dispute whether the specification disclosed human anti-CGRP antagonist
`antibodies: such antibodies are not explicitly referenced, but the technology to humanize
`antibodies was “routine” and discussed in the specification. Compare [ECF No. 400 ¶ 205] with
`[id. ¶ P66, P96].
`9 Lilly purports to object to Paragraph P135, [ECF No. 400 ¶ 135], however, Lilly does not
`dispute that the specification includes specific examples of formulations for common modes of
`administration. Rather, Lilly argues that the specification “offer[s] no support to show that the
`inventors made anti-CGRP antibody formulations that included all possible routes of
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`8
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`(12) describes how anti-CGRP antagonist antibodies can be used to treat headache by
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`administering an anti-CGRP antagonist antibody to a patient prior to, during and/or after
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`headache, [id. ¶ P134]; and (13) reports activity of Antibody G1 in two assays conducted in rats:
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`a saphenous nerve assay and a closed cranial window assay, [id. ¶ 214].10
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`Teva currently has an antibody product within the scope of its patents called Ajovy®
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`(Fremanezumab), that is prescribed to treat migraine. [ECF No. 400 ¶ 375].
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`iv.
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`Information Omitted from the Specification
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`Lilly alleges that by not disclosing certain information in the shared specification of the
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`Patents-in-Suit, Teva engaged in inequitable conduct. [ECF No. 387 ¶ 13]. In particular, Lilly
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`points to the fact that named inventors, Drs. Zeller and Pons, did not, in the ’045 patent, disclose
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`to the U.S. Patent and Trademark Office (“PTO”) prior art literature of which they were aware,
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`specifically, Shaw et al., The effect of monoclonal antibodies to calcitonin gene-related peptide
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`administration in the art” and claims that “Teva’s inventors testified to not having made any anti-
`CGRP antibody formulations for certain routes of administration known in the art.” [Id.].
`Neither of Lilly’s assertions, however, disputes Teva’s claim that the specification includes
`specific examples of formulations for common modes of administration.
`10 The saphenous nerve assay tests whether an anti-CGRP antibody can inhibit CGRP biological
`function in a live animal at a site of action relevant to migraine, whereas the closed cranial
`window assay measures the effect of an anti-CGRP antagonist antibody on the dilation of dural
`arteries, which is known to be associated with head pain. Teva asserts that a positive result in the
`closed cranial window assay was understood to be predictive of efficacy for treating migraine in
`humans, and although Lilly does not directly dispute this statement, Lilly claims the assertion is
`contradicted by Teva’s expert who testified that “preclinical animal experiments [] will never
`satisfy concerns about efficacy and safety . . . .” [Id. ¶ P79]. Lilly further claims that Teva’s
`statement is unsupported because its specification states that “the precise pathophysiology of
`migraine is not yet well understood.” [Id.]. The Court notes that neither piece of testimony cited
`by Lilly actually contradicts Teva’s statement and therefore finds that the Teva’s assertion—that
`a positive result in the closed cranial window assay was understood to be predictive of
`efficacy—is not disputed. Teva acknowledges that the specification does not disclose any
`experiment involving administration of anti-CGRP antibodies to non-human primates or humans.
`[ECF No. 411 ¶¶ 196–97]. The parties do dispute, however, whether the results from the assay
`address the blood-brain barrier (“BBB”). Cf. [ECF No. 400 ¶ 219] with [id. ¶ 115].
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`9
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`(CGRP) on CGRP-induced vasodilation in pig coronary artery rings, 106 Br. J. Pharmacol. 196,
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`196–98 (1992) (“Shaw”), which taught, in part, that no antibody studied in the paper that bound
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`to the mid-region of CGRP had blocked CGRP activity. [Id.]. Lilly further asserts that Drs.
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`Zeller and Pons committed inequitable conduct by not disclosing to the PTO (1) the results of
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`experiments that showed that some N-terminal antibodies bind to but, nevertheless, do not
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`antagonize CGRP, [ECF No. 348-1 at 9]; see [ECF No. 387 ¶ 40]; (2) certain non-C-terminal
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`binding data that addressed polyclonal antibodies, [ECF No. 387 ¶ 41; ECF No. 348-1 at 9]; and
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`(3) data from a cortical spreading depression (“CSD”) assay, [ECF No. 387 ¶ 15; ECF No. 348 at
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`11]. With regard to this last point, the CSD assay was, at the time, a preferred in vivo test used to
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`evaluate migraine pathophysiology because it allowed researchers to, among other things,
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`evaluate whether a drug could effect a particular migraine symptom. [ECF No. 387 ¶ 53]. Lilly
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`claims that Dr. Pons was on notice of the importance of the test because he was on an email
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`chain in which another scientist stated that if the anti-CGRP antibody “doesn’t work” in the
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`assay, “then the whole concept is questionable.” [Id. ¶ 57 (quoting ECF No. 354-26)]. Lilly’s
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`expert Dr. Charles described the CSD assay results as “material” in his report, which, in his
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`view, meant that the information was “germane to the patent issue.” [Id. ¶ 28 (quoting ECF No.
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`304-18)]. The parties dispute whether the results of the CSD assay were either inconclusive
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`because the experiment lacked a control (Teva’s position) or negative (Lilly’s position), and
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`whether a negative result means that the antibody does not work to treat migraine. [Id. ¶¶ 54–
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`56].
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`F.
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`Lilly’s Development of Emgality® (Galcanezumab) and Knowledge of Teva’s
`Patents
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`In 2004, Lilly began a program to develop an anti-CGRP antagonist antibody for the
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`therapeutic treatment of migraine, which eventually led to the creation of Emgality. [ECF No.
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`10
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`395 ¶ 21]. During this process Lilly successfully generated murine antibodies that bound to the
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`mid-region of CGRP, screened them for CGRP antagonism, and ultimately humanized an
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`antibody that was later named Galcanezumab. [Id. ¶¶ 28–32]. Lilly did not create
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`Galcanezumab, however, until 2008–2009.11 [Id. ¶ P4]. Lilly also applied for and was granted a
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`patent (U.S. Patent No. 9,505,838 (the “’838 patent”)) directed to the use of Galcanezumab to
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`treat migraine. [ECF No. 406 ¶ 125]. Galcanezumab is the only therapeutic antibody approved
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`by the FDA to treat episodic cluster headache. [ECF No. 411 ¶ 311].
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`Lilly had knowledge of the ’045 patent at least as early as October 24, 2017, and
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`knowledge of the ’907 and ’908 patents as early as February 6, 2018. [ECF No. 395 ¶ P1]. As
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`discussed above, the Patents-in-Suit claim priority to the ’809 application, [id. ¶ P2], which
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`shares the same specification as the Patents-in-Suit. [Id. ¶ P3]. Lilly was aware of the ’809
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`application as of June 7, 2011. [Id. ¶ P5].
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`G.
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`Lilly’s Marketing and Sale of Emgality®
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`Lilly has continuously made, marketed, and sold Emgality since October 2018. [ECF
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`No. 395 ¶ P13]. Leading up to the launch in 2018, Lilly undertook a sales and marketing
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`campaign to promote its product. See [id. ¶ P14].12
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`Lilly’s campaign included spending $523.5 million on marketing between 2018 and
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`2020, [ECF No. 395 ¶ P14], and nearly $225 million on its U.S. Emgality sales force in that
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`same time period, [id ¶ P15]. Internal documents also state that Lilly’s focus was on “strategic
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`objectives to ‘Win’ and ‘Grow’ the CGRP class,” [id. ¶ P17 (quoting ECF No. 368-82)], and
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`11 Lilly selected a lead murine antibody for humanization in April 2008, and later decided to
`advance the resulting humanized compound to clinical development in December 2009. [ECF
`No. 395 ¶ P4].
`12 Lilly raises objections to this statement of fact, but does not dispute the underlying assertion
`that it engaged in a marketing campaign to promote Emgality.
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`11
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`describe the U.S. Emgality campaign as having a “land grab” mentality at the time the product
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`launched, [id. ¶ P18 (quoting ECF No. 368-80) (exhibit to witness deposition)]. Lilly’s
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`campaign also involved providing free samples to healthcare providers and offering increased
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`rebates to pharmacy benefits managers to ensure that health insurance formularies would cover
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`Emgality. [Id. ¶ P23–24].
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`H.
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`Procedural Background
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`Teva initiated this lawsuit on September 27, 2018, claiming that Lilly infringed nine of
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`Teva’s patents. [ECF No. 411 ¶ 2]. Soon after, Lilly responded by filing a petition for IPR by
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`the Patent Trial and Appeal Board (“PTAB”) of the three Patents-in-Suit (the “Method of
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`Treatment patents”) as well as an additional six patents (the “Composition of Matter patents”).
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`[Id. ¶¶ 3–4]. The Composition of Matter patents and the Method of Treatment patents are
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`directed at the same type of antibodies. [Id. ¶ P3].13
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`During the Composition of Matter IPR proceedings, Lilly argued that it would have been
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`obvious to make a humanized anti-CGRP antibody within the scope of the claims, [ECF No. 290
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`at 16–17], and that “by 2005, conventional humanization techniques were routinely used that
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`preserved the affinity and specificity of the donor antibody[,]” see [ECF No. 411 ¶ P8]. Lilly
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`further claimed that a person of ordinary skill in the art (“POSA”)14 “would have had a
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`reasonable expectation of successfully making a humanized anti-CGRP antagonist antibody.”
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`13 Although Lilly objects to Teva’s statement of fact, it does not dispute that the type of antibody
`at issue in the Composition of Matter patents (i.e., human and/or humanized anti-CGRP
`antagonist antibodies) are also at issue in the Patents-in-Suit. See [ECF No. 411 ¶ 10].
`14 The parties agree that a person of ordinary skill in the art would have either (1) a Ph.D. in a
`relevant field such as immunology, biochemistry, or pharmacology, with several years of post-
`doctoral experience in antibody engineering, pharmacokinetics, and pharmacodynamics, or (2)
`an M.D. with a residency or specialty in neurology, and several years of experience studying
`CGRP or treating patients with a CGRP-related disease, such as migraine headaches. [ECF No.
`411 ¶¶ 223–24].
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`
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`12
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`

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`Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 13 of 53
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`
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`[Id. ¶ P9 (citing ECF No. 368-2 at 95, 98; ECF No. 368-3 at 104–06)]. During the proceedings,
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`Teva argued that the challenged patents represented “the first time that anyone, anywhere in the
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`world developed a humanized anti-CGRP antibody that could successfully be used as a human
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`therapeutic.” [Id. ¶ 7 (quoting ECF No. 292-15 at 6)]. The PTAB sided with Lilly and found
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`that the six Composition of Matter patents were unpatentable as obvious. [Id. ¶ P4]. In so
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`concluding, it found that “anti-CGRP antagonist antibodies were well known in the art, and that
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`the art encouraged the development of humanized anti-CGRP antibodies.” [Id. ¶ P5 (quoting
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`ECF No. 368-2 at 95)]. Teva appealed the PTAB’s decision, and the Federal Circuit affirmed.
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`[Id. ¶ 16].
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`The Method of Treatment patents, generally speaking, are directed to the treatment of
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`headache disorders with antibodies that bind to CGRP and inhibit its function. [ECF No. 387 ¶
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`8].15 In the Method of Treatment IPR proceedings, Teva argued that the patents were not
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`obvious as a POSA “would not have used a full-length antibody to treat migraine because it
`
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`15 Lilly claims to dispute Paragraph 8 of Teva’s statement of material facts, see [ECF No. 387 at
`3–4], which states, “The patent claims at issue in this case are directed to treating migraines by
`using antibodies that bind to the peptide [CGRP] and inhibit its function.” Upon review,
`however, Lilly’s response does not raise any dispute and merely quibbles about whether CGRP
`is a singular peptide and repeats Lilly’s argument that Teva’s antibodies bind only to the C-
`terminal end of CGRP whereas other antibodies inhibit CGRP by binding to its middle-region or
`N-terminal end. [Id.]. To begin, it is not clear that Teva’s statement asserts that CGRP is
`singular, therefore Lilly’s claim that CGRP “consists of alpha and beta isoforms” does not
`necessarily reflect a dispute. [Id. at 4]. Moreover, even if there was a dispute, “[a] ‘material
`fact’ is one that ‘might affect the outcome’ of the case[,]” Intercontinental Great Brands LLC v.
`Kellogg N. Am. Co., 869 F.3d 1336, 1343 (Fed. Cir. 2017) (quoting Anderson v. Liberty Lobby,
`Inc., 477 U.S. 242, 248 (1986)), and whether CGRP is singular does not impact the Court’s
`analysis of the issues presently before it. Teva’s statement also does not make any claim as to
`which portion of CGRP the antibodies bind, therefore Lilly’s discussion of antibodies that bind
`to the N-terminal and mid-region does not evidence a dispute. Lilly further argues that Teva’s
`statement is disputed because the claims in the Patents-in-Suit are directed towards treating other
`headache conditions in addition to migraine. [Id. at 4]. That assertion, however, does not
`dispute that the facts set forth in Paragraph 8, i.e., that the Patents-in-Suit pertain to the use of
`antibodies to treat migraine by binding and inhibiting CGRP.
`
`
`
`13
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`

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`Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 14 of 53
`Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 14 of 53
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`would not have been expected to cross the [blood brain barrier (“BBB”)].” [ECF No. 400 § P18
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`(quoting ECF No. 296-17 at 9)]. The PTAB agreed, finding that uncertainty about whether
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`antibodies would need to cross the BBB weighedagainst a reasonable expectation of success in
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`using the claimed methods, and therefore weighed against obviousness. [Id. J P20]. Lilly
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`appealed and the Federal Circuit affirmed. [Id. § P17].
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`The parties have now filed six cross-motions for summary judgment. Teva’s motions
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`argue that Lilly should be judicially estopped from raising arguments contrary to the positionsit
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`advanced in the IPR proceedings and that Lilly cannot succeed onits inequitable conduct claims.
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`Lilly’s motions contend that its product, Emgality, does not infringe, willfully or otherwise, the
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`claims of the Patents-in-Suit and, alternatively, that Teva’s patents are invalid for lack of written
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`description and lack of enablement.
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`Il.
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`STANDARD OF REVIEW
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`Summary judgmentis appropriate where the moving party can showthat“there is no
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`genuine dispute as to any material fact and the movantis entitled to judgment as a matter of
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`law.” Fed. R. Civ. P. 56(a). “[A]n issue is ‘genuine’ if it ‘may reasonably be resolved in favor
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`ofeither party.”” Robinson v. Cook, 863 F. Supp. 2d 49, 60 (D. Mass. 2012) (quoting Vineberg
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`v. Bissonnette, 548 F.3d 50, 56 (1st Cir. 2008)). “A fact is material if its resolution might affect
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`the outcome of the case underthe controlling law.” Cochran v. Quest Software, Inc., 328 F.3d 1,
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`6 (Ist Cir. 2003) (citation omitted). By invoking summary judgment, “the movingparty in effect
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`declares that the evidenceis insufficient to support the nonmoving party’s case.” United States
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`v. One Parcel of Real Prop. (Great Harbor Neck, New Shoreham, R.L.), 960 F.2d 200, 204 (1st
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`Cir. 1992) (citing Celotex Corp. v. Catrett, 477 U.S. 317, 325 (1986)).
`
`14
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`

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`Case 1:18-cv-12029-ADB Document 513 Filed 10/03/22 Page 15 of 53
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`
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`“To succeed in showing that there is no genuine dispute of material fact, the moving
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`party must . . . ‘affirmatively produce evidence that negates an essential element of the non-
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`moving party’s claim,’ or, using ‘evidentiary materials already on file . . . demonstrate that the
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`non-moving party will be unable to carry its burden of persuasion at trial.’” Ocasio-Hernández
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`v. Fortuño-Burset, 777 F.3d 1, 4–5 (1st Cir. 2015) (quoting Carmona v. Toledo, 215 F.3d 124,
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`132 (1st Cir. 2000)).
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`Conversely, “[t]o defeat a properly supported motion for summary judgment, the
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`no