Case 1:17-cv-01672-GMS Document 1 Filed 11/17/17 Page 1 of 58 PageID #: 1
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`GENENTECH, INC. and CITY OF HOPE,
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`Plaintiffs,
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`v.
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`PFIZER, INC.,
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`Defendant.
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`
`Civil Action No. ___________
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`
`
`
`
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`COMPLAINT
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`Plaintiffs Genentech, Inc. (“Genentech”) and City of Hope bring this Complaint for
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`declaratory and injunctive relief against Defendant Pfizer, Inc. to address Pfizer’s infringement
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`of 40 patents relating to Genentech’s groundbreaking breast cancer drug Herceptin®.
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`
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`NATURE OF THE CASE
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`1.
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`Breast cancer is a serious disease affecting over 2.8 million women in the United
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`States. Approximately 20-25% of those women suffer from “HER2-positive” breast cancer.
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`This is a particularly aggressive form of the disease characterized by overexpression of human
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`epidermal growth factor receptor 2 (i.e., “HER2”) proteins due to excessive HER2 gene
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`amplification.
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`2.
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`In the early 1990s, a diagnosis of HER2-positive breast cancer was effectively a
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`death sentence: patients had an average life expectancy of only 18 months. The quality of life
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`for those patients was markedly poor—the disease rapidly metastasized (i.e., spread to other
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`parts of the body). The only available treatments were invasive and disfiguring surgery and
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`chemotherapeutic drugs with harsh side effects, and those treatments added little to the patient’s
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`life span.
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`1
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`3.
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`The treatment of HER2-positive breast cancer, and the lives of millions of women
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`suffering from the disease, changed dramatically with Genentech’s development of Herceptin®.
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`Herceptin® was the first drug of its kind—an antibody called trastuzumab that specifically
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`targeted the biological mechanism that makes HER2-positive breast cancer such an aggressive
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`form of the disease.
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`4.
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`Although the scientific community was initially skeptical that such an antibody-
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`based therapy could work, Genentech’s specific methods of using Herceptin® proved remarkably
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`effective. Indeed, after Genentech revealed the results of its clinical studies, the scientific
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`community hailed Herceptin® as “the beginning of a whole new wave of biological drugs that
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`modulate the causes of cancer”1 and a sign that “the whole field of cancer research has turned a
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`corner.”2
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`5.
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`Since FDA approval of Herceptin® in 1998, Genentech has worked diligently to
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`develop new methods of using Herceptin®—including improved dosing schedules and broader
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`indications—to expand access to therapy and improve the quality of life for millions of patients
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`worldwide. This research has greatly expanded the number of patients who are able to benefit
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`from Herceptin®. To further expand access to this lifesaving drug, Genentech also provides
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`Herceptin® free of charge to patients who are uninsured or cannot afford treatment and assists
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`with out-of-pocket prescription-related expenses. All told, Genentech has spent over two
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`decades, and billions of dollars, developing Herceptin® into the life-saving drug it is today.
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`6.
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`Genentech’s groundbreaking work developing Herceptin® was the result of years
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`of research from a group of talented scientists. The United States Patent and Trademark Office
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`1 Gina Kolata and Lawrence M. Fisher, Drugs to Fight Breast Cancer Near Approval, NEW
`YORK TIMES (FRONT PAGE) (Sept. 3, 1998).
`2 Robert Langreth, Breast-Cancer Drug Is Backed by FDA Panel, Wall Street J. (Sept. 3, 1998).
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`2
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`recognized that innovative work by granting Genentech numerous patents claiming Herceptin®,
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`its manufacture, and its use. And as one of the pioneers in the biotechnology field, Genentech
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`collaborated with scientists at research institutions such as the City of Hope to make foundational
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`inventions, such as efficient techniques for making antibodies that can be used as drugs.
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`7.
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`Seeking to profit from the success of Plaintiffs’ innovations, Pfizer is seeking
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`FDA approval of a biosimilar version of Herceptin® called PF-05280014. PF-05280014 is a
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`copycat product for which Pfizer is seeking the same label indications and usage as Herceptin®.
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`In fact, Pfizer is relying upon Genentech’s own studies demonstrating the safety and efficacy of
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`Herceptin® to obtain approval of its biosimilar product.
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`8.
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`
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`In 2010, Congress provided a pathway for resolving patent disputes relating to
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`biosimilar products through the Biologics Price Competition and Innovation Act (“BPCIA”).
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`Pursuant to the process outlined in the BPCIA, biosimilar applicants and innovator companies
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`exchange certain information concerning the biosimilar product and the patents that may be
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`infringed by the manufacture and sale of the biosimilar product. See 42 U.S.C. § 262(l). On
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`November 17, 2017 Pfizer purported to provide Genentech with a notice pursuant to 42 U.S.C.
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`§ 262(l)(8)(A) that it intends to market PF-05280014 in the United States.
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`9.
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`Plaintiffs thus seek a judgment that Pfizer’s submission of the aBLA to obtain
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`approval to engage in the commercial manufacture, use, offer to sell, or sale of the Pfizer aBLA
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`product prior to the expiration of the Genentech patents described below infringes those patents
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`under 35 U.S.C. § 271(e)(2)(C)(i). Plaintiffs also seek a permanent injunction barring Pfizer’s
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`manufacture, use, offer to sell, sale, or importation of its biosimilar product prior to the
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`expiration of those patents. In the event that Pfizer launches its biosimilar product prior to the
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`3
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`expiration of those patents, Plaintiffs also seek monetary damages, including its lost profits, and
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`any further relief as this Court may deem just and proper.
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`PARTIES
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`Plaintiff Genentech, Inc. is a corporation organized and existing under the laws of
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`10.
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`the State of Delaware with its corporate headquarters at 1 DNA Way, South San Francisco,
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`California 94080.
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`11.
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`Genentech was founded in 1976 and for four decades has been at the forefront of
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`innovation in the field of therapeutic biotechnology. Today, Genentech employs a large number
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`of researchers, scientists and post-doctoral staff members who routinely publish in top peer-
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`reviewed journals and are among the leaders in total citations to their work by researchers.
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`Genentech currently markets numerous approved pharmaceutical and biologic drugs for a range
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`of serious or life-threatening medical conditions, including various forms of cancer, heart
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`attacks, strokes, rheumatoid arthritis, and respiratory diseases.
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`12.
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`Plaintiff City of Hope is a California not-for-profit organization, with its principal
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`place of business at 1500 East Duarte Road, Duarte, California 91010.
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`13.
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`Founded in 1913, the City of Hope is a leading research hospital that incorporates
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`cutting-edge research into patient care for cancer, diabetes, and other serious diseases.
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`14.
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`Upon information and belief, Defendant Pfizer, Inc. is a company organized and
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`existing under the laws of the State of Delaware with its principal place of business located at
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`235 East 42nd Street, New York, NY 10017.
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`15.
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`Pfizer, Inc. is, among other things, engaged in the development of biologic drugs,
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`including a proposed biosimilar version of Genentech’s Herceptin® product, PF-05280014
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`4
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`(“Pfizer’s aBLA product”). Upon information and belief, Pfizer’s aBLA product will be
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`distributed and sold in the State of Delaware and throughout the United States.
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`JURISDICTION AND VENUE
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`This action arises under the BPCIA, 42 U.S.C. § 262(l) and the Patent Laws of the
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`16.
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`United States, Title 35, United States Code. This Court has subject matter jurisdiction pursuant
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`to 28 U.S.C. §§ 1331 and 1338.
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`17.
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`Venue is proper with respect to Pfizer, Inc. in this Court pursuant to 28 U.S.C. §
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`1400(b) because Pfizer is incorporated in Delaware.
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`18.
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`
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`This Court has personal jurisdiction over Pfizer because it is incorporated in
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`Delaware. In addition, among other things, Pfizer has filed an Abbreviated Biologics License
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`Application (“aBLA”) No. 761081 with the FDA seeking approval to market its aBLA product,
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`which reliably indicates that it will market its proposed biosimilar product in Delaware if
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`approved.
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`THE PARTIES’ EXCHANGES UNDER THE BPCIA
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`Pfizer submitted aBLA number 761081 to the FDA seeking approval for the
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`19.
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`commercial manufacture, use, offer for sale, or sale of the Pfizer aBLA product, a biosimilar
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`version of trastuzumab, which is subject to BLA No. 103792 to Genentech, Inc.
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`20.
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`21.
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`
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`The FDA accepted Pfizer’s aBLA for review on August 21, 2017.
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`On August 28, 2017, Pfizer’s outside counsel sent a letter to Genentech regarding
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`the provision of a copy of Pfizer’s aBLA for PF-05280014.
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`22.
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`On September 5, 2017, Pfizer provided Genentech with a copy of Pfizer’s aBLA,
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`which included a small amount of manufacturing information.
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`5
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`23.
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`Genentech responded on October 19, 2017 to identify deficiencies in Pfizer’s
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`production of manufacturing information and request specific information concerning the
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`manufacture of Pfizer’s biosimilar product. Pfizer provided some additional manufacturing
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`information on November 1, 2017, but did not satisfy its disclosure obligations. Genentech then
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`responded on November 3, 2017 to explain that Pfizer’s November 1, 2017 production was
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`deficient in that it failed to provide all of the requested information in contravention of 42 U.S.C.
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`§ 262(l)(2).
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`24.
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`Pfizer did not disclose all of the information relevant to establishing whether the
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`manufacture of Pfizer’s aBLA product will infringe each of the patents identified on Genentech’s
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`operative list pursuant to 42 U.S.C. § 262(l)(3)(A), despite Genentech’s request that Pfizer
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`provide “other information that describes the process or processes used to manufacture” as
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`required by 42 U.S.C. § 262(l)(A). Pfizer’s failure to provide sufficient information under those
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`circumstances justifies Genentech’s contention that manufacturing Pfizer’s aBLA product will
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`infringe such patents.
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`25.
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`Despite Pfizer’s non-compliance (and without waiving Genentech’s objection to
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`such non-compliance), Genentech provided its operative list of patents pursuant to 42 U.S.C. §
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`262(l)(3)(A) on November 3, 2017.
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`26.
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`On November 17, 2017, Pfizer notified Genentech pursuant to 42 U.S.C.
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`§ 262(l)(8)(A) that it intends to commence commercial marketing of PF-05280014 in the United
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`States. See Exhibit A. To date, Pfizer has not provided its detailed statement concerning non-
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`infringement and invalidity pursuant to 42 U.S.C. § 262(l)(3)(B) for the patents on Genentech’s
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`patent list.
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`6
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`PFIZER’S aBLA PRODUCT
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`Pfizer has publicly states that its aBLA product is biosimilar to Herceptin®. For
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`27.
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`example, Pfizer has issued press releases claiming that PF-05280014 is “a potential biosimilar to
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`Herceptin®”3 and an “investigational trastuzumab biosimilar,”4 and it has announced the results
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`of a Pfizer study that purports to conclude that “there were no clinically meaningful differences
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`between PF-05280014 and Herceptin.”5 Given Pfizer’s claim of biosimilarity, Pfizer’s aBLA
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`product must “utilize the same mechanism or mechanisms of action [as Herceptin®] for the
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`condition or conditions of use prescribed, recommended, or suggested in the proposed labeling.”
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`42 U.S.C. § 262(k)(2)(A)(i)(II).
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`28.
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`Under 35 U.S.C. § 271(e)(2)(C), Pfizer has committed a statutory act of patent
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`infringement with respect to patents identified by Genentech under 42 U.S.C. § 262(l)(3),
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`through the submission of its aBLA application for PF-05280014.
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`GENENTECH’S ASSERTED PATENTS
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`Genentech has spent over two decades and significant resources developing
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`29.
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`Herceptin®, and the USPTO has awarded to Genentech numerous patents on innovations
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`resulting from this massive undertaking. These patents cover the antibody trastuzumab, along
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`with its manufacture and use.
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`30.
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`Upon information and belief, Pfizer’s aBLA product will infringe at least the
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`following patents, which Genentech has asserted in this lawsuit: U.S. Patent No. 6,331,415, U.S.
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`3 https://www.pfizer.com/news/press-release/press-release-
`detail/pfizer_announces_positive_top_line_results_from_the_pivotal_comparative_reflections_b
`3271002_study_for_pf_05280014_a_potential_biosimilar_to_herceptin_1_trastuzumab
`4 https://investors.pfizer.com/investor-news/press-release-details/2017/Pfizer-Presents-Positive-
`Pivotal-Data-for-PF-05280014-an-Investigational-Biosimilar-to-Herceptin-trastuzumab-at-the-
`European-Society-for-Medical-Oncology-ESMO-2017-Congress/default.aspx
`5 Id.
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`7
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`Patent No. 7,923,221, U.S. Patent No. 6,407,213, U.S. Patent No. 7,846,441, U.S. Patent No.
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`7,892,549, U.S. Patent No. 6,627,196, U.S. Patent No. 7,371,379, U.S. Patent No. 6,339,142,
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`U.S. Patent No. 6,417,335, U.S. Patent No. 6,489,447, U.S. Patent No. 9,249,218, U.S. Patent
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`No. 8,574,869, U.S. Patent No. 6,620,918, U.S. Patent No. 7,485,704, U.S. Patent No. 7,807,799,
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`U.S. Patent No. 8,633,302, U.S. Patent No. 8,691,232, U.S. Patent No. 8,771,988, U.S. Patent
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`No. 8,822,655, U.S. Patent No. 9,428,766, U.S. Patent No. 9,487,809, U.S. Patent No. 9,714,293,
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`U.S. Patent No. 7,449,184, U.S. Patent No. 7,501,122, U.S. Patent No. 7,993,834, U.S. Patent
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`No. 8,076,066, U.S. Patent No. 8,425,908, U.S. Patent No. 8,440,402, U.S. Patent No. 8,460,895,
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`U.S. Patent No. 8,512,983, U.S. Patent No. 6,121,428, U.S. Patent No. 6,242,177, U.S. Patent
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`No. 6,586,206, U.S. Patent No. 6,610,516, U.S. Patent No. 6,716,602, U.S. Patent No. 7,390,660,
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`U.S. Patent No. 8,044,017, U.S. Patent No. 8,314,225, U.S. Patent No. 8,710,196, and U.S.
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`Patent No. 9,493,744.
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`The Cabilly Patents
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`U.S. Patent Nos. 6,331,415 and 7,923,221 (collectively, the “Cabilly Patents”)
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`31.
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`describe and claim a process for producing monoclonal antibodies, such as Herceptin®, from
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`recombinant DNA. This effective and efficient process applies a novel co-expression technique
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`to produce antibody heavy and light chains in a single host cell, and has given rise to an entire
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`industry of therapeutic monoclonal antibodies.
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`32.
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`U.S. Patent No. 6,331,415 (“the ’415 patent”), titled “Methods of Producing
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`Immunoglobulins, Vectors and Transformed Host Cells for Use Therein,” was duly and legally
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`issued by the Patent Office on December 18, 2001. A true and correct copy of the ’415 patent is
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`attached as Exhibit B. Genentech and the City of Hope are the owners by assignment of the ’415
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`patent.
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`8
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`33.
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`U.S. Patent No. 7,923,221 (“the ’221 patent”), titled “Methods of Making
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`Antibody Heavy and Light Chains Having Specificity for a Desired Antigen,” was duly and
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`legally issued by the Patent Office on April 12, 2011. A true and correct copy of the ’221 patent
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`is attached as Exhibit C. Genentech and the City of Hope are the owners by assignment of the
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`’221 patent.
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`The ’213 Patent
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`U.S. Patent No. 6,407,213 (“the ’213 patent”) claims the Herceptin® antibody
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`34.
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`itself, along with other humanized monoclonal antibodies. The inventors of the ’213 patent
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`discovered that by grafting the key parts of a mouse antibody onto a human antibody consensus
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`sequence, they could create antibodies that were both tolerated by the immune system and
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`effective to treat diseases like HER2-positive breast cancer. The techniques described in the
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`’213 patent allowed scientists to efficiently design antibodies for specific disease targets by
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`modifying mouse antibodies produced in the laboratory in specific ways so that they are
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`compatible with a human immune system.
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`35.
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`The ’213 patent, titled “Method for Making Humanized Antibodies,” was duly
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`and legally issued by the Patent Office on June 18, 2002. A true and correct copy of the ’213
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`patent is attached as Exhibit D. Genentech is the owner by assignment of the ’213 patent.
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`The Combination Chemotherapy Patents
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`U.S. Patent No. 7,846,441 (“the ’441 patent”), claims the administration of
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`36.
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`Herceptin® in combination with a chemotherapy agent known as a taxoid, in the absence of an
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`anthracycline derivative (another chemotherapy agent) in an amount effective to extend time to
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`disease progression without overall increase in severe adverse events. This specific method of
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`treatment unexpectedly resulted in a significant improvement in patient outcomes. It nearly
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`9
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`doubled the time until disease progression compared to treatment using a taxoid alone, and it also
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`avoided the serious cardiotoxicity associated with Herceptin® in combination with anthracycline
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`derivatives that unexpectedly presented during the Herceptin® clinical trials.
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`37.
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`The ’441 patent, titled “Treatment with Anti-ErbB2 Antibodies,” was duly and
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`legally issued by the Patent Office on December 7, 2010. A true and correct copy of the ’441
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`patent is attached as Exhibit E. Genentech is the owner by assignment of the ’441 patent.
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`38.
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` U.S. Patent No. 7,892,549 (“the ’549 patent”) is a continuation to the ’441 patent
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`that claims a method of treating a patient with HER2-positive breast cancer by administering
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`Herceptin® in combination with a taxoid and a further growth inhibitory agent or further
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`therapeutic agent.
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`39.
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`The ’549 patent, titled “Treatment with Anti-ErbB2 Antibodies,” was duly and
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`legally issued by the Patent Office on February 22, 2011. A true and correct copy of the ’549
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`patent is attached as Exhibit F. Genentech is the owner by assignment of the ’549 patent.
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`40.
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`U.S. Patent No. 8,425,908 (“the ’908 patent”), claims priority to the same
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`provisional application as the ’441 and ’549 patents. The ’908 patent claims a method of treating
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`a patient with HER2-positive gastric cancer by administering Herceptin® in combination with
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`chemotherapy and in the absence of an anthracycline derivative.
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`41.
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`The ’908 patent, titled “Treatment with Anti-ErbB2 Antibodies,” was duly and
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`legally issued by the Patent Office on April 23, 2013. A true and correct copy of the ’908 patent
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`is attached as Exhibit G. Genentech is the owner by assignment of the ’908 patent.
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`The Method of Administration Patents
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`U.S. Patent Nos. 6,627,196 and 7,371,379 (collectively, the “Method of
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`42.
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`
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`Administration Patents”) cover the most common administration method for Herceptin®: an
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`10
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`initial dose of 8 mg/kg, followed by 6 mg/kg doses once every three weeks. Herceptin® was
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`initially approved for administration on a weekly regimen, but Genentech discovered that the
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`drug could be dosed only once every three weeks without reducing safety or effectiveness. The
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`discovery of three-weekly dosing has had a marked impact on patients’ quality of life by
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`providing the same life-saving effects of Herceptin® while allowing patients to receive treatment
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`less frequently.
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`43.
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`U.S. Patent No. 6,627,196 (“the ’196 patent”), titled “Dosages for Treatment with
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`Anti-ErbB2 Antibodies,” was duly and legally issued by the Patent Office on September 30,
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`2003. A true and correct copy of the ’196 patent is attached as Exhibit H. Genentech is the
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`owner by assignment of the ’196 patent.
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`44.
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`U.S. Patent No. 7,371,379 (“the ’379 patent”), titled “Dosages for Treatment with
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`Anti-ErbB2 Antibodies,” was duly and legally issued by the Patent Office on May 13, 2008. A
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`true and correct copy of the ’379 patent is attached as Exhibit I. Genentech is the owner by
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`assignment of the ’379 patent.
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`The Acidic Variants Patents
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`U.S. Patent Nos. 6,339,142; 6,417,335; 6,489,447; and 9,249,218 (collectively,
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`45.
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`the “Acidic Variants Patents”) cover compositions with reduced amounts of more acidic
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`structural variants of trastuzumab (“acidic variants”) and chromatographic processes for
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`removing these acidic variants during purification. Some trastuzumab acidic variants have lower
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`potency than trastuzumab itself. The Acidic Variants Patents describe and claim
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`chromatographic processes and compositions that ensure the Herceptin® drug product is
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`uniformly pure and effective.
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`11
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`46.
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`
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`U.S. Patent No. 6,339,142 (“the ’142 patent”), titled “Protein Purification,” was
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`duly and legally issued by the Patent Office on January 15, 2002. A true and correct copy of the
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`’142 patent is attached as Exhibit J. Genentech is the owner by assignment of the ’142 patent.
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`47.
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`
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`U.S. Patent No. 6,417,335 (“the ’335 patent”), titled “Protein Purification,” was
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`duly and legally issued by the Patent Office on July 9, 2002. A true and correct copy of the ’335
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`patent is attached as Exhibit K. Genentech is the owner by assignment of the ’335 patent.
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`48.
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`
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`U.S. Patent No. 6,489,447 (“the ’447 patent”), titled “Protein Purification,” was
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`duly and legally issued by the Patent Office on December 3, 2002. A true and correct copy of
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`the ’447 patent is attached as Exhibit L. Genentech is the owner by assignment of the ’447
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`patent.
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`49.
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`U.S. Patent No. 9,249,218 (“the ’218 patent”), titled “Protein Purification,” was
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`duly and legally issued by the Patent Office on February 2, 2016. A true and correct copy of the
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`’218 patent is attached as Exhibit M. Genentech is the owner by assignment of the ’218 patent.
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`
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`Combination Therapy with Perjeta
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`50.
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`U.S. Patent Nos. 7,501,122, 7,449,184, and 8,691,232 claim novel therapies
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`combining trastuzumab with another anti-HER2 antibody developed by Genentech called
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`pertuzumab. That combination therapy is a common method of treatment for HER2-positive
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`breast cancer patients involving Herceptin®.
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`51.
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`
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`U.S. Patent No. 7,501,122 (“the ’122 patent”), titled “Treatment with Anti-ErbB2
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`Antibody Combinations,” was duly and legally issued by the Patent Office on March 10, 2009.
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`A true and correct copy of the ’122 patent is attached as Exhibit N. Genentech is the owner by
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`assignment of the ’122 patent.
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`12
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`52.
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`
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`U.S. Patent No. 7,449,184 (“the ’184 patent”), titled “Fixed Dosing of HER
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`Antibodies,” was duly and legally issued by the Patent Office on November 11, 2008. A true
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`and correct copy of the ’184 patent is attached as Exhibit O. Genentech is the owner by
`
`assignment of the ’184 patent.
`
`
`53.
`
`U.S. Patent No. 8,691,232 (“the ’232 patent”), titled “Extending Time to Disease
`
`Progression or Survival in Cancer Patients,” was duly and legally issued by the Patent Office on
`
`April 8, 2014. A true and correct copy of the ’232 patent is attached as Exhibit P. Genentech is
`
`the owner by assignment of the ’232 patent.
`
`HER2 Diagnostic Patents
`
`U.S. Patent Nos. 7,993,834; 8,076,066; and 8,440,402 claim novel techniques for
`
`
`54.
`
`identifying patients who might benefit from trastuzumab therapy using gene amplification
`
`techniques even where immunohistochemistry techniques suggest that the patient may not
`
`overexpress HER2.
`
`
`55.
`
`U.S. Patent No. 7,993,834 (“the ’834 patent”), titled “Detection of ErbB2 Gene
`
`Amplification to Increase the Likelihood of the Effectiveness of ErbB2 Antibody Breast Cancer
`
`Therapy,” was duly and legally issued by the Patent Office on August 9, 2011. A true and
`
`correct copy of the ’834 patent is attached as Exhibit Q. Genentech is the owner by assignment
`
`of the ’834 patent.
`
`
`56.
`
`U.S. Patent No. 8,076,066 (“the ’066 patent”), titled “Gene Detection Assay for
`
`Improving the Likelihood of an Effective Response to a HER2 Antibody Cancer Therapy,” was
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`duly and legally issued by the Patent Office on December 13, 2011. A true and correct copy of
`
`the ’066 patent is attached as Exhibit R. Genentech is the owner by assignment of the ’066
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`patent.
`
`13
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`Case 1:17-cv-01672-GMS Document 1 Filed 11/17/17 Page 14 of 58 PageID #: 14
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`57.
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`
`
`U.S. Patent No. 8,440,402 (“the ’402 patent”), titled “Gene Detection Assay for
`
`Improving the Likelihood of an Effective Response to a HER2 Antibody Cancer Therapy,” was
`
`duly and legally issued by the Patent Office on May 14, 2013. A true and correct copy of the
`
`’402 patent is attached as Exhibit S. Genentech is the owner by assignment of the ’402 patent.
`
`Cell Culture, Purification, and Antibody Manufacturing Patents
`
`U.S. Patent Nos. 6,242,177, 6,586,206, 6,610,516, 6,716,602, 7,390,660,
`
`58.
`
`
`
`8,460,895, 8,512,983, 8,574,869, 8,771,988, 9,428,766, 9,487,809, 9,714,293, 6,121,428,
`
`6,620,918, 7,485,704, 7,807,799, 8,633,302, 8,822,655, 8,044,017, 8,314,225, 8,710,196, and
`
`9,493,744 claim novel techniques developed by Genentech relating to various aspects of cell
`
`culture, purification, and antibody purification.
`
`
`59.
`
`U.S. Patent No. 6,620,918 (“the ’918 patent”), titled “Separation of Polypeptide
`
`Monomers,” was duly and legally issued by the Patent Office on September 16, 2003. A true
`
`and correct copy of the ’918 patent is attached as Exhibit T. Genentech is the owner by
`
`assignment of the ’918 patent.
`
`
`60.
`
`U.S. Patent No. 7,485,704 (“the ’704 patent”), titled “Reducing Protein A
`
`Leaching During Protein A Affinity Chromatography,” was duly and legally issued by the Patent
`
`Office on February 3, 2009. A true and correct copy of the ’704 patent is attached as Exhibit U.
`
`Genentech is the owner by assignment of the ’704 patent.
`
`61.
`
`
`
`U.S. Patent No. 7,807,799 (“the ’799 patent”), titled “Reducing Protein A
`
`Leaching During Protein A Affinity Chromatography,” was duly and legally issued by the Patent
`
`Office on October 5, 2010. A true and correct copy of the ’799 patent is attached as Exhibit V.
`
`Genentech is the owner by assignment of the ’799 patent.
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`14
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`Case 1:17-cv-01672-GMS Document 1 Filed 11/17/17 Page 15 of 58 PageID #: 15
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`62.
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`
`
`U.S. Patent No. 8,044,017 (“the ’017 patent”), titled “Protein Purification,” was
`
`duly and legally issued by the Patent Office on October 25, 2011. A true and correct copy of the
`
`’017 patent is attached as Exhibit W. Genentech is the owner by assignment of the ’017 patent.
`
`63.
`
`
`
`U.S. Patent No. 6,242,177 (“the ’177 patent”), titled “Methods and Compositions
`
`for Secretion of Heterologous Polypeptides,” was duly and legally issued by the Patent Office on
`
`June 5, 2001. A true and correct copy of the ’177 patent is attached as Exhibit X. Genentech is
`
`the owner by assignment of the ’177 patent.
`
`
`64.
`
`U.S. Patent No. 6,586,206 (“the ’206 patent”), titled “Methods for Making
`
`Recombinant Proteins Using Apoptosis Inhibitors,” was duly and legally issued by the Patent
`
`Office on July 1, 2003. A true and correct copy of the ’206 patent is attached as Exhibit Y.
`
`Genentech is the owner by assignment of the ’206 patent.
`
`
`65.
`
`U.S. Patent No. 6,610,516 (“the ’516 patent”), titled “Cell Culture Process,” was
`
`duly and legally issued by the Patent Office on August 26, 2003. A true and correct copy of the
`
`’516 patent is attached as Exhibit Z. Genentech is the owner by assignment of the ’516 patent.
`
`
`66.
`
`U.S. Patent No. 6,716,602 (“the ’602 patent”), titled “Metabolic Rate Shifts in
`
`Fermentations Expressing Recombinant Proteins,” was duly and legally issued by the Patent
`
`Office on April 6, 2004. A true and correct copy of the ’602 patent is attached as Exhibit AA.
`
`Genentech is the owner by assignment of the ’602 patent.
`
`
`67.
`
`U.S. Patent No. 7,390,660 (“the ’660 patent”), titled “Methods for Growing
`
`Mammalian Cells In Vitro,” was duly and legally issued by the Patent Office on June 24, 2008.
`
`A true and correct copy of the ’660 patent is attached as Exhibit BB. The ’660 patent is assigned
`
`to Hoffmann-La Roche, Inc., and Genentech is the exclusive licensee with the right to enforce
`
`the ’660 patent.
`
`15
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`Case 1:17-cv-01672-GMS Document 1 Filed 11/17/17 Page 16 of 58 PageID #: 16
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`68.
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`
`
`U.S. Patent No. 8,460,895 (“the ’895 patent”), titled “Method for Producing
`
`Recombinant Proteins with a Constant Content of pCO.sub.2 in the Medium,” was duly and
`
`legally issued by the Patent Office on June 11, 2013. A true and correct copy of the ’895 patent
`
`is attached as Exhibit CC. The ’895 patent is assigned to Hoffmann-La Roche, Inc., and
`
`Genentech is the exclusive licensee with the right to enforce the ’895 patent.
`
`
`69.
`
`U.S. Patent No. 8,512,983 (“the ’983 patent”), titled “Production of Proteins in
`
`Glutamine-Free Cell Culture Media,” was duly and legally issued by the Patent Office on August
`
`20, 2013. A true and correct copy of the ’983 patent is attached as Exhibit DD. Genentech is the
`
`owner by assignment of the ’983 patent.
`
`
`70.
`
`U.S. Patent No. 8,574,869 (“the ’869 patent”), titled “Prevention of Disulfide
`
`Bond Reduction During Recombinant Production of Polypeptides,” was duly and legally issued
`
`by the Patent Office on November 5, 2013. A true and correct copy of the ’869 patent is
`
`attached as Exhibit EE. Genentech is the owner by assignment of the ’869 patent.
`
`
`71.
`
`U.S. Patent No. 8,771,988 (“the ’988 patent”), titled “Protein Expression From
`
`Multiple Nucleic Acids,” was duly and legally issued by the Patent Office on July 8, 2014. A
`
`true and correct copy of the ’988 patent is attached as Exhibit FF. The ’988 patent is assigned to
`
`Hoffmann-La Roche, Inc., and Genentech is the exclusive licensee with the right to enforce the
`
`’988 patent.
`
`
`72.
`
`U.S. Patent No. 8,314,225 (“the ’225 patent”), titled “Heavy Chain Mutant
`
`Leading to Improved Immunoglobulin Production,” was duly and legally issued by the Patent
`
`Office on November 20, 2012. A true and correct copy of the ’225 patent is attached as Exhibit
`
`GG. The ’225 patent is assigned to Hoffmann-La Roche, Inc., and Genentech is the exclusive
`
`licensee with the right to enforce the ’225 patent.
`
`16
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`Case 1:17-cv-01672-GMS Document 1 Filed 11/17/17 Page 17 of 58 PageID #: 17
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`73.
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`
`
`U.S. Patent No. 9,428,766 (“the ’766 patent”), titled “Protein Expression From
`
`Multiple Nucleic Acids,” was duly and legally issued by the Patent Office on August 30, 2016.
`
`A true and correct copy of the ’766 patent is attached as Exhibit HH. The ’766 patent is assigned
`
`to Hoffmann-La Roche, Inc., and Genentech is the exclusive licensee with the right to enforce
`
`the ’766 patent.
`
`
`74.
`
`U.S. Patent No. 9,487,809 (“the ’809 patent”), titled “Decreasing Lactate Level
`
`and Increasing Polypeptide Production by Downregulating the Expression of Lactate
`
`Dehydrogenase and Pyruvate Dehydrogenase Kinase,” was duly and legally issued by the Patent
`
`Office on November 8, 2016. A true and correct copy of the ’809 patent is attached as Exhibit II.
`
`Genentech is the owner by assignment of the ’809 patent.
`
`
`75.
`
`U.S. Patent No. 9,714,293 (“the ’293 patent”), titled “Production of Proteins in
`
`Glutamine-Free Cell Culture Media,” was duly and legally issued by the Patent Office on July
`
`25, 2017. A true and correct copy of the ’293 patent is attached as Exhibit JJ. Genentech is the
`
`owner by assignment of the ’293 patent.
`
`
`76.
`
`U.S. Patent No. 6,121,428 (“the ’428 patent”), titled “Protein Recovery,” was
`
`duly and legally issued by the Patent Office on September 19, 2000. A true and correct copy of
`
`the ’428 patent is attached as Exhibit KK. Genentech is the owner by assignment of the ’428
`
`patent.
`
`
`77.
`
`U.S. Patent No. 8,710,196 (“the cell culture ’196 patent”), titled “Protein
`
`Purification,” was duly and legally issued by the Patent Office on April 29, 2014. A true and
`
`correct copy of the