Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 1 of 34
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF MASSACHUSETTS
`
`GENENTECH, INC., HOFFMANN-LA
`ROCHE, INC., and CHUGAI
`PHARMACEUTICAL CO., LTD,
`
`Plaintiffs,
`
`v.
`
`BIOGEN MA INC and BIO-THERA
`SOLUTIONS, LTD.,
`
`Defendants.
`
`Case No.:
`
`JURY TRIAL DEMANDED
`
`COMPLAINT FOR PATENT INFRINGEMENT
`
`Plaintiff Genentech, Inc. (“Genentech”) is licensed by the U.S. Food and Drug
`
`Administration (“FDA”) to make and sell Actemra®, a treatment for rheumatoid arthritis and
`
`other serious inflammatory diseases. Defendant Biogen MA Inc. (“Biogen”) is seeking FDA
`
`approval under the Biologics Price Competition and Innovation Act (“BPCIA”), 42 U.S.C. §§
`
`262(k)-(l), to commercialize “BIIB800,” a proposed biosimilar to Genentech’s drug Actemra®
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`(tocilizumab). To vindicate their patent rights, Plaintiffs bring this Complaint seeking a
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`judgment of patent infringement against Defendants under 35 U.S.C. § 271(e) and the BPCIA.
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`THE PARTIES, JURISDICTION, AND VENUE
`
`1.
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`Genentech is a corporation organized under the laws of the State of Delaware
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`with its principal place of business at 1 DNA Way, South San Francisco, California 94080. The
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`company is dedicated to discovering, developing, and commercializing medicines to treat
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`patients with debilitating and life-threatening diseases.
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`2.
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`Hoffmann-La Roche, Inc. (“HLR”) is a corporation organized under the laws of
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`the State of New Jersey with its principal place of business is 150 Clove Road, Little Falls, New
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`1
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 2 of 34
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`Jersey, 07424.
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`3.
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`Chugai Pharmaceutical Co., Ltd (“Chugai”) is a corporation organized under the
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`laws of Japan. Chugai’s principal place of business is 1-1 Nihonbashi-Muromachi 2-chome,
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`Chuo-ku, Tokyo 103-8324 Japan.
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`4.
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`For ease of reference, Genentech, HLR, and Chugai are referred to herein
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`collectively as “Plaintiffs.”
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`5.
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`Biogen is a corporation organized under the laws of the Commonwealth of
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`Massachusetts with its principal place of business is 225 Binney Street, Cambridge,
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`Massachusetts 02142 United States.
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`6.
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`Biogen develops, manufactures, distributes, sells, and/or imports drug products
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`for the entire United States market and, on information and belief, does business in every state,
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`including Massachusetts, either directly or indirectly.
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`7.
`
`On information and belief, Bio-Thera Solutions, Ltd. (“Bio-Thera”) is a
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`corporation organized and existing under the laws of China, having its corporate offices and
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`principal place of business at Floor 5, Building A6, 11 Kai-Yuan Blvd, Huangpu District,
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`Guangzhou, China.
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`8.
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`On information and belief, Bio-Thera is in the business of, among other things,
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`developing and manufacturing biosimilars of branded pharmaceutical drug products for
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`marketing by others throughout the United States, including Massachusetts.
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`9.
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`On information and belief, Bio-Thera manufactures BIIB800 for Biogen pursuant
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`to the specifications provided in Biogen’s biosimilar application to file a more abbreviated
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`Biologics License Application (“aBLA”) pursuant to 42 U.S.C. § 262(k) and will participate in
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`the importation of BIIB800 into the United States. On information and belief, FDA will inspect
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 3 of 34
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`Bio-Thera’s production facilities as part of FDA’s consideration of Biogen’s aBLA.
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`10.
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`On information and belief, Biogen and Bio-Thera acted in concert to prepare and
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`submit Biogen’s aBLA to FDA. Bio-Thera prepared, created, approved, and/or assembled
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`documentation in support of Biogen’s aBLA. For example, several of the documents included
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`within Biogen’s aBLA indicate that they were generated by Bio-Thera and describe activities
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`performed by Bio-Thera.
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`11.
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`On information and belief, Bio-Thera actively encouraged, recommended, and/or
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`promoted that Biogen prepare and submit Biogen’s aBLA to FDA.
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`12.
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`On information and belief, Biogen and Bio-Thera know and intend that upon
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`FDA approval of Biogen’s aBLA, Bio-Thera will manufacture BIIB800; and Biogen will
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`directly or indirectly market, sell, and distribute BIIB800 throughout the United States, including
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`in Massachusetts.
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`13.
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`On information and belief, following any FDA approval of BIIB800, Biogen and
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`Bio-Thera will act in concert to distribute and sell BIIB800 throughout the United States,
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`including within Massachusetts.
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`14.
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`For ease of reference, Biogen and Bio-Thera are referred to herein collectively as
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`“Defendants.”
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`15.
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`Plaintiffs’ claims for patent infringement arise under the patent laws of the United
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`States, Title 35 of the United States Code, Title 42 of the United States Code, and the
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`Declaratory Judgment Act, 28 U.S.C. §§ 2201-2202. This Court therefore has subject matter
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`jurisdiction pursuant to 28 U.S.C. §§ 1331 and 1338(a).
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`16.
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`This Court has personal jurisdiction over Biogen because it is incorporated in
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`Massachusetts and has its principal place of business in Massachusetts; because Biogen is
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 4 of 34
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`seeking approval to engage in the commercial manufacture, use, offer for sale, sale, and/or
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`importation of BIIB800 in the United States, including in the Commonwealth of Massachusetts;
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`and because, if its product receives FDA approval, Biogen intends to market, distribute, offer for
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`sale, and/or sell it in the United States, including in the Commonwealth of Massachusetts,
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`deriving substantial revenue therefrom.
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`17.
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`Because Biogen has its principal place of business in this District, venue is proper
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`under 28 U.S.C. §§ 1391 and 1400(b).
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`18.
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`This Court has personal jurisdiction over Bio-Thera because, among other things,
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`Bio-Thera, itself and in concert with Biogen, has purposefully availed itself of the benefits and
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`protections of Massachusetts’s laws such that it should reasonably anticipate being haled into
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`court in Massachusetts. On information and belief, Bio-Thera, in concert with Biogen, is seeking
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`approval to engage in the commercial manufacture of BIIB800 for distribution in the United
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`States, including in Massachusetts; and because, if BIIB800 receives FDA approval, Bio-Thera
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`will facilitate Biogen’s marketing, distribution, offer for sale, and/or sale of it in the United
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`States, including in Massachusetts, deriving substantial revenue therefrom.
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`19.
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`Venue is proper in this District under 28 U.S.C. §§ 1391 and 1400(b) with respect
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`to Bio-Thera at least because, on information and belief, Bio-Thera is a foreign corporation that
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`may be sued in any judicial district in which it is subject to the Court’s personal jurisdiction.
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`FACTUAL BASIS FOR RELIEF
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`20.
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`The active ingredient of Actemra®, tocilizumab, is a genetically engineered
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`antibody that inhibits the biological activity of the cytokine interleukin 6 (“IL-6”). Within the
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`human body, IL-6 signaling can lead to chronic inflammation. Tocilizumab treats this
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`inflammation by binding to IL-6 receptors and disrupting this biologic activity.
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`21.
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`Following over a decade of research and development, Genentech filed
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 5 of 34
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`Biologics License Application No. 125276 with FDA with respect to Actemra®. In 2010, FDA
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`approved Actemra® for the treatment of rheumatoid arthritis based on several Phase 3 clinical
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`trials. Those studies demonstrated that unlike conventional therapies for RA that focused on
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`relieving pain, Actemra® was found to inhibit progression of structural joint damage, improve the
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`functionality of joints, as well as improve patients’ pain and quality of life.
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`22.
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`Since then, FDA has approved Actemra® for the treatment of several
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`additional indications including Systemic Juvenile Idiopathic Arthritis, Polyarticular Juvenile
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`Idiopathic Arthritis, Giant Cell Arteritis, CAR T Cell-Induced Cytokine Release Syndrome, and
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`Systemic Sclerosis-Associated Interstitial Lung Disease. Most recently, Actemra® helped to
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`address the COVID-19 pandemic and has been approved to treat COVID-19 in hospitalized
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`adults.
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`23.
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`The BPCIA provides for a substantially abbreviated regulatory approval
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`pathway for biosimilars by allowing applicants rely on the extensive clinical testing previously
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`conducted, at great expense, by the innovator company that developed the medicine the applicant
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`wants to copy. Rather than seeking approval for the drug by filing a traditional Biologics
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`License Application pursuant to 42 U.S.C. § 262(a), the BPCIA permits a biosimilar applicant to
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`file an aBLA pursuant to 42 U.S.C. § 262(k).
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`24.
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`In exchange for this accelerated and less expensive application process, the
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`BPCIA obligates a biosimilar applicant to address a reference product sponsor’s relevant patents
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`in a manner that permits adjudication of patent rights before commercialization of the biosimilar
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`product. The BPCIA does so through its so-called “patent dance.”
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`25.
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`The BPCIA requires (i) the biosimilar applicant to provide its aBLA as well as
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`other information that describes the process or processes used to manufacture the biological
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`product that is the subject of such application to the innovator company (referred to in the statute
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`as the “reference product sponsor,” or “RPS”); (ii) the RPS to identify patents it owns or
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`exclusively licenses that it reasonably believes the biosimilar would infringe; and (iii) both sides
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`prior to any litigation to exchange their respective infringement and validity positions. See 42
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`U.S.C. § 262(l).
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`26.
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`The BPCIA also requires the applicant to provide the reference product sponsor
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`180-days advance notice before commencing sales of any approved biosimilar. This statutory
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`mechanism allows the RPS to file suit and seek a timely and unhurried hearing on a motion to
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`preliminarily enjoin a product launch “until the court decides the issue of patent validity,
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`enforcement, and infringement with respect to any patent” the RPS has identified. 42 U.S.C.
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`§ 262 (l)(8)(A), (B).
`
`27.
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`The first step in the statutory patent dance required Biogen, within 20 days of
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`when FDA accepted its application, to supply Genentech with the aBLA for BIIB800 as well as
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`“such other information that describes the process or processes used to manufacture
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`the biological product that is the subject of such application.” 42 U.S.C. § 262(l)(2)(A).
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`Although Biogen provided Genentech with its aBLA, Biogen failed to provide “such other
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`information.” For example, Biogen failed to identify with particularity the chemicals it provides
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`to its genetically-engineered cells when cultivating those cells to make its tocilizumab. This is
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`precisely the type of information necessary to “describe the process or processes used to
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`manufacture the biological product” and the type of information relevant to assessing whether
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`Biogen infringes various patents, described further below.
`
`28.
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`Biogen’s aBLA does make clear that Biogen itself does not directly make its
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`tocilizumab product. Rather, Bio-Thera Solutions Ltd, a Chinese company, makes BIIB800 at
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`facilities in Guangzhou, China. Based on public statements regarding the contractual
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`relationship between Biogen and Bio-Thera,1 Bio-Thera’s activities are performed on behalf of
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`Biogen, for Biogen’s benefit, and pursuant to the specifications provided in Biogen’s aBLA, and
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`thus Bio-Thera’s manufacturing activities are under Biogen’s direction and control. In exchange,
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`Bio-Thera stands to receive “potential milestone payments” and “tiered royalties” if Biogen
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`commercializes BIIB800 in the United States.
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`29.
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`After receipt of Biogen’s aBLA on December 12, 2022, Genentech complained to
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`Biogen that its production excluded “other information” about the manufacturing process for
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`BIIB800 that was necessary for Genentech to evaluate the full scope of infringement of its
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`patents. Genentech requested that Biogen provide such information, for example, on January 23,
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`2023, February 1, 2023, and February 8, 2023. Biogen declined to provide the requested
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`information. Reserving its rights for that production failure, Genentech supplied Biogen with a
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`list of patents for which “a claim of patent infringement could reasonably be asserted” if Biogen
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`commercialized its product. 42 U.S.C. § 262(l)(3)(A).
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`30.
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`Upon receiving Genentech’s patent lists, Biogen was required by the BPCIA to
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`serve “detailed statements” for the patents on the original list. By statute, a biosimilar
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`applicant’s detailed statements must either represent that it will not begin commercial marketing
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`of its biosimilar product before the patent expires (under 42 U.S.C. § 262(l)(3)(B)(ii)(II)) or
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`allege that the patent is invalid or not infringed (under § 262(l)(3)(B)(ii)(I)). On April 11, 2023,
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`Biogen purported to serve “detailed statements” regarding the listed patents. Biogen’s
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`statements lacked the level of factual detail required by § 262(l)(3)(B).
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`1 For example, Biogen’s press release at: https://investors.biogen.com/news-releases/news-
`release-details/biogen-and-bio-thera-solutions-announce-commercialization-and
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`31.
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`Pursuant to § 262(l)(3)(C), Genentech timely provided its detailed responses to
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`Biogen’s contentions, setting forth particular grounds for infringement based on the confidential
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`information in Biogen’s aBLA and rebutting Biogen’s noninfringement and invalidity
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`allegations. Because Genentech has already served upon Biogen hundreds of pages of detailed
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`(l)(3)(C) contentions setting forth and putting Biogen on notice of the factual and legal basis for
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`the allegations made in this lawsuit, the infringement allegations set forth below do not repeat
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`any specific content of Biogen’s aBLA, which Biogen has designated as confidential under 42
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`U.S.C. § 262(l)(1)(A).
`
`32.
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`Pursuant to § 262(l)(4)(A), the parties negotiated regarding which patents on
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`Genentech’s list should be litigated in a § 271(e) infringement action. On June 27, 2023, Biogen
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`sent Genentech a letter indicating that the parties had failed to agree upon a list of patents and
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`selecting a number of patents as to which the parties would then be required to exchange lists
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`pursuant to § 262(l)(5). The patents that were identified on one or both of the parties’ lists are
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`listed in the next section of the Complaint.
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`PLAINTIFFS’ PATENTS
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`33.
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`Biologic medicines like tocilizumab are complex. The innovative work done to
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`develop tocilizumab has been recognized by the Patent Office with multiple patents covering
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`various aspects of making and using the drug.
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`34.
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`Because Biogen has not complied with its production obligation under 42 U.S.C.
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`§ 262(l), Genentech has been forced to assess Biogen’s infringement based on incomplete
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`information, including, but not limited to, the above-described materials it sent to and received
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`from Biogen. Nevertheless, based on, among other things, such materials, Genentech has reason
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`to believe that the manufacture, use, sale, or offer for sale, or importation of BIIB800 has or will
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`infringe U.S. Patent Nos. 7,332,289; 7,521,052; 8,398,980; 8,512,983; 8,574,869; 8,734,800;
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`8
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 9 of 34
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`9,714,293; 9,902,777; 10,017,732; 10,336,983; 10,501,769; 10,662,237; 10,676,710; 10,744,201;
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`10,829,732; 10,982,003; 11,021,728; 11,078,294; 11,136,610; and 11,377,678. Copies of these
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`patents are attached to this Complaint as Exhibits 1-20.
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`35.
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`The Asserted Patents are each owned by one or more of Plaintiffs, and none of
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`them has yet expired. To the extent that Genentech is not the owner of an Asserted Patent, it is
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`the exclusive licensee of that patent with respect to tocilizumab with the right to enforce that
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`patent against Biogen pursuant to a patent licensing agreement with Chugai Pharmaceutical Co.,
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`Ltd. and Hoffmann-La Roche, Inc.
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`FIRST CAUSE OF ACTION
`(INFRINGEMENT OF THE ’289 PATENT)
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
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`United States Patent No. 7,332,289 (the “’289 patent”) (Exhibit 1), was duly and
`
`36.
`
`37.
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`legally issued on February 19, 2008 and is unexpired.
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`38.
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`The ’289 patent was included on the list of patents provided by Genentech to
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`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`39.
`
`Claim 1 of the ’289 is exemplary. It recites:
`
`A method for removing contaminant DNA in an antibody-
`containing sample, which comprises the followings steps:
`1)
`applying
`the
`antibody-containing
`sample
`to
`chromatography on Protein A or Protein G;
`2) eluting the antibody with an acidic aqueous solution of low
`conductivity having a molarity of 100 mM or less;
`3) neutralizing the eluate from step (2) to form particles by addition
`of a buffer to raise the pH to 4 to 8, wherein the molarity of the
`neutralized eluate is 100 mM or less; and
`4) removing the particles to thereby remove contaminant DNA from
`the antibody-containing sample.
`
`affinity
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`40.
`
`Based on the information presently available to Plaintiffs, including the
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`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2),
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`and on Plaintiffs’ reasonable belief with respect to matters as to which Biogen has elected not to
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`disclose information about its processes, the manufacturing process used by Biogen and Bio-
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`Thera to make its tocilizumab biosimilar is covered by at least Claim 1 of the ’052 patent.
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`41.
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`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to obtain
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`FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale, or
`
`import into the United States, of BIIB800 before the expiration of the ’289 patent is also an act
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`of infringement of one or more claims of the ’289 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`42.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
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`infringing one or more claims of the ’289 patent. Genentech has no adequate remedy at law.
`
`Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and §
`
`271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`SECOND CAUSE OF ACTION
`(INFRINGEMENT OF THE ’052 PATENT)
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
`
`United States Patent No. 7,521,052 (the “’052 patent”) (Exhibit 2), was duly and
`
`43.
`
`44.
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`legally issued on April 21, 2009 and is unexpired.
`
`45.
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`The ’052 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`46.
`
`Claim 1 of the ’052 is exemplary. It recites:
`
`rheumatoid arthritis, comprising
`treating
`for
`A method
`administering an effective amount of an anti-IL-6 receptor antibody
`(anti-IL-6R antibody) and an effective amount of methotrexate
`(MTX) to a patient in need thereof, wherein the anti-IL-6R antibody
`is a humanized PM-1 antibody.
`
`47.
`
`Based on the information presently available to Plaintiffs, including the
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 11 of 34
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`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2),
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`the method of using Biogen’s tocilizumab product instructed by Biogen’s proposed labeling is
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`covered by at least claim 1.
`
`48.
`
`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to obtain
`
`FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale, or
`
`import into the United States, of BIIB800 before the expiration of the ’052 patent is also an act
`
`of infringement of one or more claims of the ’052 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`49.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
`
`infringing one or more claims of the ’052 patent. Genentech has no adequate remedy at
`
`law. Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and §
`
`271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`THIRD CAUSE OF ACTION
`(INFRINGEMENT OF THE ’980 PATENT)
`
`Plaintiffs incorporate paragraph 1-35 as if set forth herein.
`
`United States Patent No. 8,398,980 (the “’980 patent”) (Exhibit 3), was duly
`
`50.
`
`51.
`
`and legally issued on March 19, 2013.
`
`52.
`
`The ’980 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`53.
`
`Claim 1 of the ’980 is exemplary. It recites:
`
`An antibody subtype (1) which is a subtype of the humanized PM-1
`antibody against interleukin-6 receptor (IL-6R) comprising a heavy
`chain that has amino acids 1-448 of the amino acid sequence set
`forth in SEQID NO: 1, a heavy chain that has amino acids 1-447 of
`the amino acid sequence set forth in SEQID NO: 1 and a C-terminal
`that is Pro-NH2 and a light chain that has the amino acid sequence
`set forth in SEQID NO: 2.
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 12 of 34
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`54.
`
`Based on the information presently available to Plaintiffs, including the
`
`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2), the
`
`tocilizumab product made by Biogen and Bio-Thera is covered by at least claim 1.
`
`55.
`
`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to
`
`obtain FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale,
`
`or import into the United States, of BIIB800 before the expiration of the ’980 patent is also an
`
`act of infringement of one or more claims of the ’980 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`56.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
`
`infringing one or more claims of the ’980 patent. Genentech has no adequate remedy at
`
`law. Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and
`
`§ 271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`FOURTH CAUSE OF ACTION
`(INFRINGEMENT OF THE ’983 PATENT)
`
`57.
`
`58.
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
`
`United States Patent No. 8,512,983 (the “’983 patent”) (Exhibit 4), was duly
`
`and legally issued on August 20, 2013.
`
`59.
`
`The ’983 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`60.
`
`Claim 1 of the ’983 is exemplary. It recites:
`
`A process for producing a polypeptide in a mammalian host cell
`expressing said polypeptide, comprising culturing the mammalian
`host cell in a production phase of the culture in a glutamine-free
`production culture medium containing asparagine, wherein the
`asparagine is added at a concentration in the range of 7.5 mM to 15
`mM.
`
`61.
`
`Based on the information presently available to Plaintiffs, including the
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`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 13 of 34
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`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2),
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`and on Plaintiffs’ reasonable belief with respect to matters as to which Biogen has elected not to
`
`disclose information about its processes, the manufacturing process used by Biogen and Bio-
`
`Thera to make its tocilizumab biosimilar is covered by at least claim 1.
`
`62.
`
`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to
`
`obtain FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale,
`
`or import into the United States, of BIIB800 before the expiration of the ’983 patent is also an
`
`act of infringement of one or more claims of the ’983 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`63.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
`
`infringing one or more claims of the ’983 patent. Genentech has no adequate remedy at
`
`law. Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and
`
`§ 271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`FIFTH CAUSE OF ACTION
`(INFRINGEMENT OF THE ’869 PATENT)
`
`64.
`
`65.
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
`
`United States Patent No. 8,574,869 (the “’869 patent”) (Exhibit 5), was duly
`
`and legally issued on November 5, 2013.
`
`66.
`
`The ’869 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`67.
`
`Claim 1 of the ’869 is exemplary. It recites:
`
`A method for the prevention of the reduction of a disulfide bond in
`an antibody expressed in a recombinant host cell, comprising,
`following fermentation, sparging the pre-harvest or harvested
`culture fluid of said recombinant host cell with air, wherein the
`amount of dissolved oxygen (dO2) in the pre-harvest or harvested
`culture fluid is at least 10%.
`
`13
`
`

`

`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 14 of 34
`
`68.
`
`Based on the information presently available to Plaintiffs, including the
`
`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2),
`
`and on Plaintiffs’ reasonable belief with respect to matters as to which Biogen has elected not to
`
`disclose information about its processes, the manufacturing process used by Biogen and Bio-
`
`Thera to make its tocilizumab biosimilar is covered by at least claim 1.
`
`69.
`
`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to
`
`obtain FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale,
`
`or import into the United States, of BIIB800 before the expiration of the ’869 patent is also an
`
`act of infringement of one or more claims of the ’869 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`70.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
`
`infringing one or more claims of the ’869 patent. Genentech has no adequate remedy at
`
`law. Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and §
`
`271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`SIXTH CAUSE OF ACTION
`(INFRINGEMENT OF THE ’800 PATENT)
`
`71.
`
`72.
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
`
`United States Patent No. 8,734,800 (the “’800 patent”) (Exhibit 6), was duly
`
`and legally issued on May 27, 2014.
`
`73.
`
`The ’800 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`74.
`
`Claim 1 of the ’800 is exemplary. It recites:
`
`A method of inhibiting biological activity of interleukin-6 receptor
`(IL-6R) with an antibody subtype against IL-6R, comprising
`contacting the IL-6R with the antibody Subtype, wherein the
`
`14
`
`

`

`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 15 of 34
`
`antibody Subtype comprises a heavy chain that has amino acids 1-
`448 of the amino acid sequence set forth in SEQID NO: 1 in which
`an N-terminal glutamine (Gln) is pyroglutamylated, a heavy chain
`that has amino acids 1-447 of the amino acid sequence set forth in
`SEQID NO: 1 in which an N-terminal glutamine (Gln) is
`pyroglutamylated and a C-terminal that is Pro-NH2, and a light chain
`that has the amino acid sequence set forth in SEQID NO: 2.
`
`75.
`
`Based on the information presently available to Plaintiffs, including the
`
`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2), the
`
`method of using Biogen’s tocilizumab product instructed by Biogen’s proposed labeling is
`
`covered by at least claim 1.
`
`76.
`
`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to
`
`obtain FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale,
`
`or import into the United States, of BIIB800 before the expiration of the ’800 patent is also an
`
`act of infringement of one or more claims of the ’800 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`77.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
`
`infringing one or more claims of the ’800 patent. Genentech has no adequate remedy at
`
`law. Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and
`
`§ 271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`SEVENTH CAUSE OF ACTION
`(INFRINGEMENT OF THE ’293 PATENT)
`
`78.
`
`79.
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
`
`United States Patent No. 9,714,293 (the “’293 patent”) (Exhibit 7), was duly
`
`and legally issued on July 25, 2017.
`
`80.
`
`The ’293 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`15
`
`

`

`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 16 of 34
`
`81.
`
`Claim 1 of the ’293 is exemplary. It recites:
`
`A process for producing a polypeptide in a host cell expressing said
`polypeptide, comprising culturing the host cell in a production phase
`of the culture in a glutamine-free production culture medium
`containing asparagine and aspartic acid, wherein the asparagine is
`added at a concentration in the range of 7.5 mM to 15 mM and
`wherein the aspartic acid is added at a concentration in the range of
`1 mM to 10 mM.
`
`82.
`
`Based on the information presently available to Plaintiffs, including the
`
`confidential information disclosed to Genentech by Biogen pursuant to 42 U.S.C. § 262(l)(2),
`
`and on Plaintiffs’ reasonable belief with respect to matters as to which Biogen has elected not to
`
`disclose information about its processes, the manufacturing process used by Biogen and Bio-
`
`Thera to make its tocilizumab biosimilar is covered by at least claim 1.
`
`83.
`
`The submission of Biogen’s aBLA by Biogen in concert with Bio-Thera to
`
`obtain FDA approval to engage in the commercial manufacture, use, offer for sale, and/or sale,
`
`or import into the United States, of BIIB800 before the expiration of the ’293 patent is also an
`
`act of infringement of one or more claims of the ’293 patent under 35 U.S.C. § 271(e)(2)(C)(i).
`
`84.
`
`Genentech will be irreparably harmed if Defendants are not enjoined from
`
`infringing one or more claims of the ’293 patent. Genentech has no adequate remedy at
`
`law. Genentech is entitled to injunctive relief at least under 35 U.S.C. § 271(e)(4)(B) and
`
`§ 271(e)(4)(D) preventing Defendants from any further infringement, damages or other monetary
`
`relief under 35 U.S.C. § 271(e)(4)(C), and fees under 35 U.S.C. § 271(e)(4) and § 285.
`
`EIGHTH CAUSE OF ACTION
`(INFRINGEMENT OF THE ’777 PATENT)
`
`85.
`
`86.
`
`Plaintiffs incorporate paragraphs 1-35 as if fully set forth herein.
`
`United States Patent No. 9,902,777 (the “’777 patent”) (Exhibit 8), was duly
`
`and legally issued on February 27, 2018.
`
`16
`
`

`

`Case 1:23-cv-11573-LTS Document 1 Filed 07/13/23 Page 17 of 34
`
`87.
`
`The ’777 patent was included on the list of patents provided by Genentech to
`
`Biogen pursuant to 42 U.S.C. § 262(l)(3)(A).
`
`88.
`
`Claim 1 of the ’777 is exemplary. It recites:
`
`A method of producing an antibody subtype 1 comprising culturing
`a host cell comprising at least one nucleic acid encoding for a heavy
`chain and at least one nucleic acid encoding for a light chain of an
`anti-IL-6R antibody, wherein said antibody subtype 1 comprises a
`heavy chain that has amino acids 1-448 of the amino acid sequence
`set forth in SEQ ID NO: 1, a heavy chain that has amino acids 1-447
`of the amino acid sequence set forth in SEQ ID NO: 1 and a C-
`terminal that is Pro-NH2, and a light chain that has the amino acid
`sequence set forth