Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 1 of 65 PageID #: 1515
`
`
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`GENENTECH, INC. and CITY OF HOPE,
`
`Plaintiffs,
`
`v.
`
`AMGEN INC.,
`
`Defendant.
`
`
`
`
`C.A. No.
`
`
`
`COMPLAINT
`
`Plaintiffs Genentech, Inc. (“Genentech”) and City of Hope (collectively, “Plaintiffs”)
`
`bring this Complaint for declaratory and injunctive relief against Defendant Amgen Inc.
`
`(“Amgen”) to address Amgen’s infringement of patents relating to Genentech’s groundbreaking
`
`breast cancer drug Herceptin®.
`
`NATURE OF THE CASE
`
`1.
`
`
`
`Breast cancer is a serious disease affecting over 2.8 million women in the United
`
`States. Approximately 20-25% of those women suffer from “HER2-positive” breast cancer.
`
`This is a particularly aggressive form of the disease characterized by overexpression of human
`
`epidermal growth factor receptor 2 (i.e., “HER2”) proteins due to excessive HER2 gene
`
`amplification.
`
`2.
`
`
`
`In the early 1990s, a diagnosis of HER2-positive breast cancer was effectively a
`
`death sentence: patients had an average life expectancy of only 18 months. The quality of life
`
`for those patients was markedly poor—the disease rapidly metastasized (i.e., spread to other
`
`parts of the body). The only available treatments were invasive and disfiguring surgery and
`
`ME1 27511836v.1
`
` 1 -
`
`
`
`18-924-GMS
`
`REDACTED PUBLIC VERSION
`FILED: JULY 2, 2018
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 2 of 65 PageID #: 1516
`
`
`
`chemotherapeutic drugs with harsh side effects, and those treatments added little to the patient’s
`
`life span.
`
`3.
`
`
`
`The treatment of HER2-positive breast cancer, and the lives of millions of women
`
`suffering from the disease, changed dramatically with Genentech’s development of Herceptin®.
`
`Herceptin® was the first drug of its kind—an antibody called trastuzumab that specifically
`
`targeted the biological mechanism that makes HER2-positive breast cancer such an aggressive
`
`form of the disease.
`
`4.
`
`
`
`Although the scientific community was initially skeptical that such an antibody-
`
`based therapy could work, Genentech’s specific methods of using Herceptin® proved remarkably
`
`effective. Indeed, after Genentech revealed the results of its clinical studies, the scientific
`
`community hailed Herceptin® as “the beginning of a whole new wave of biological drugs that
`
`modulate the causes of cancer”1 and a sign that “the whole field of cancer research has turned a
`
`corner.”2
`
`5.
`
`
`
`Since FDA approval of Herceptin® in 1998, Genentech has worked diligently to
`
`develop new methods of using Herceptin®—including improved dosing schedules and broader
`
`indications—to expand access to therapy and improve the quality of life for millions of patients
`
`worldwide. This research has greatly expanded the number of patients who are able to benefit
`
`from Herceptin®. To further expand access to this lifesaving drug, Genentech also provides
`
`Herceptin® free of charge to patients who are uninsured or cannot afford treatment and assists
`
`with out-of-pocket prescription-related expenses. All told, Genentech has spent over two
`
`decades, and billions of dollars, developing Herceptin® into the life-saving drug it is today.
`
`
`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).
`
`ME1 27511836v.1
`
` 2 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 3 of 65 PageID #: 1517
`
`
`
`6.
`
`
`
`Genentech’s groundbreaking work developing Herceptin® was the result of years
`
`of research from a group of talented scientists. The United States Patent and Trademark Office
`
`recognized that innovative work by granting Genentech numerous patents claiming Herceptin®,
`
`its manufacture, and its use. And as one of the pioneers in the biotechnology field, Genentech
`
`collaborated with scientists at research institutions such as the City of Hope to make foundational
`
`inventions, such as efficient techniques for making antibodies that can be used as drugs.
`
`7.
`
`
`
`Seeking to profit from the success of Plaintiffs’ innovations, Amgen is seeking
`
`FDA approval of a biosimilar version of Herceptin® called ABP 980. ABP 980 is a copycat
`
`product for which Amgen is seeking the same label indications and usage as Herceptin®. In fact,
`
`Amgen is relying upon Genentech’s own studies demonstrating the safety and efficacy of
`
`Herceptin® to obtain approval of its biosimilar product.
`
`8.
`
`
`
`In 2010, Congress provided a pathway for resolving patent disputes relating to
`
`biosimilar products through the Biologics Price Competition and Innovation Act (“BPCIA”).
`
`Amgen initially purported to follow the process outlined in the BPCIA, which requires biosimilar
`
`applicants and innovator companies to exchange certain information concerning the biosimilar
`
`product and the patents that may be infringed by the manufacture and sale of the biosimilar
`
`product. See 42 U.S.C. § 262(l).
`
`9.
`
`
`
`Plaintiffs thus bring this action for infringement pursuant to 35 U.S.C. § 271(e)(2)
`
`based upon Amgen’s submission of its aBLA for ABP 980. Plaintiffs also seek a declaratory
`
`judgment pursuant to 42 U.S.C. § 262(l)(9) and 28 U.S.C. § 2201 that the manufacture, use, offer
`
`to sell, sale, or importation into the United States of Amgen’s biosimilar product would infringe
`
`the patents described below. Pursuant to 35 U.S.C. § 271(e)(4)(B), 42 U.S.C. § 262(l)(8)(B), 35
`
`U.S.C. § 271(a), (b), and/or 35 U.S.C. § 283, Plaintiffs also seek a preliminary and/or permanent
`
`ME1 27511836v.1
`
` 3 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 4 of 65 PageID #: 1518
`
`
`
`injunction barring Amgen’s manufacture, use, offer to sell, sale, or importation of its biosimilar
`
`product prior to the expiration of those patents. In the event that Amgen imports, manufactures,
`
`or launches its biosimilar product, and/or otherwise practices the patented inventions in the
`
`United States prior to the expiration of those patents, Plaintiffs also seek monetary damages,
`
`including lost profits, and any further relief as this Court may deem just and proper.
`
`PARTIES
`
`10.
`
`
`
`Plaintiff Genentech is a corporation organized and existing under the laws of the
`
`State of Delaware with its corporate headquarters at 1 DNA Way, South San Francisco,
`
`California 94080.
`
`11.
`
`
`
`Genentech was founded in 1976 and for four decades has been at the forefront of
`
`innovation in the field of therapeutic biotechnology. Today, Genentech employs a large number
`
`of researchers, scientists, and post-doctoral staff members who routinely publish in top peer-
`
`reviewed journals and are among the leaders in total citations to their work by researchers.
`
`Genentech currently markets numerous approved pharmaceutical and biologic drugs for a range
`
`of serious or life-threatening medical conditions, including various forms of cancer, heart
`
`attacks, strokes, rheumatoid arthritis, and respiratory diseases.
`
`12.
`
`
`
`Plaintiff City of Hope is a California not-for-profit organization, with its principal
`
`place of business at 1500 East Duarte Road, Duarte, California 91010.
`
`13.
`
`
`
`Founded in 1913, the City of Hope is a leading research hospital that incorporates
`
`cutting-edge research into patient care for cancer, diabetes, and other serious diseases.
`
`14.
`
`
`
`Upon information and belief, Defendant Amgen is a company organized and
`
`existing under the laws of the State of Delaware with its principal place of business located at
`
`One Amgen Center Drive, Thousand Oaks, California 91320.
`
`ME1 27511836v.1
`
` 4 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 5 of 65 PageID #: 1519
`
`
`
`15.
`
`
`
`Amgen is, among other things, engaged in the development of biologic drugs,
`
`including a proposed biosimilar version of Genentech’s Herceptin® product, ABP 980
`
`(“Amgen’s aBLA product”). Upon information and belief, Amgen’s aBLA product will be
`
`distributed and sold in the State of Delaware and throughout the United States.
`
`JURISDICTION AND VENUE
`
`16.
`
`
`
`This action arises under the BPCIA, 42 U.S.C. § 262(l) and the Patent Laws of the
`
`United States, Title 35, United States Code, and the Declaratory Judgment Act, 28 U.S.C.
`
`§§ 2201-2202. This Court has subject matter jurisdiction pursuant to 28 U.S.C. §§ 1331, 1332,
`
`and 1338.
`
`17.
`
`
`
`Venue is proper with respect to Amgen in this Court pursuant to 28 U.S.C.
`
`§§ 1391 and 1400(b) because Amgen is incorporated in Delaware.
`
`18.
`
`
`
`This Court has personal jurisdiction over Amgen because it is incorporated in
`
`Delaware. In addition, among other things, Amgen has filed an Abbreviated Biologics License
`
`Application (“aBLA”) for ABP 980 with the FDA seeking approval to market it, which reliably
`
`indicates that it will market its proposed biosimilar product in Delaware if approved.
`
`THE PARTIES’ EXCHANGES UNDER THE BPCIA
`
`19.
`
`
`
`On July 31, 2017, Amgen announced that it had submitted an aBLA for ABP 980
`
`to the FDA seeking approval for the commercial manufacture, use, offer for sale, or sale of the
`
`Amgen aBLA product, a biosimilar version of trastuzumab, which is subject to BLA No. 103792
`
`to Genentech.3
`
`20.
`
`
`
`The FDA accepted Amgen’s aBLA for review
`
`
`
`
`3 http://www.amgen.com/media/news-releases/2017/07/amgen-and-allergan-submit-biosimilar-
`biologics-license-application-for-abp-980-to-us-food-and-drug-administration/
`
`ME1 27511836v.1
`
` 5 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 6 of 65 PageID #: 1520
`
`
`
`21.
`
`
`
`On October 16, 2017, Amgen provided Genentech with a copy of Amgen’s
`
`aBLA, which included a small amount of manufacturing information.
`
`22.
`
`
`
`On November 3, 2017, Amgen provided Genentech with additional
`
`manufacturing information regarding Amgen’s aBLA product.
`
`23.
`
`
`
`Genentech responded on November 20, 2017, to identify deficiencies in Amgen’s
`
`production of manufacturing information and request specific information concerning the
`
`manufacture of Amgen’s biosimilar product. Amgen provided additional manufacturing
`
`information on December 1, 2017, and December 4, 2017, but did not satisfy its disclosure
`
`obligations. Genentech then responded on December 15, 2017, to explain that Amgen’s
`
`production was deficient in that it failed to provide all of the requested information in
`
`contravention of 42 U.S.C. § 262(l)(2).
`
`24.
`
`
`
`Amgen did not disclose all of the information relevant to establishing whether the
`
`manufacture of Amgen’s aBLA product will infringe each of the patents identified on
`
`Genentech’s operative list pursuant to 42 U.S.C. § 262(l)(3)(A), despite Genentech’s request that
`
`Amgen provide sufficient “other information that describes the process or processes used to
`
`manufacture” as required by 42 U.S.C. § 262(l)(A). Amgen’s failure to provide sufficient
`
`information under those circumstances justifies Genentech’s contention that manufacturing
`
`Amgen’s aBLA product will infringe such patents.
`
`25.
`
`
`
`Despite Amgen’s non-compliance (and without waiving Genentech’s objection to
`
`such non-compliance), Genentech provided its operative list of 36 patents pursuant to 42 U.S.C.
`
`§ 262(l)(3)(A) on December 15, 2017.
`
`ME1 27511836v.1
`
` 6 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 7 of 65 PageID #: 1521
`
`
`
`26.
`
`
`
`Amgen replied on December 20, 2017, to assert its position that it had complied
`
`with its disclosure obligations based on Amgen’s earlier production of its aBLA and two
`
`manufacturing documents.
`
`27.
`
`
`
`Genentech responded on December 27, 2017, to reiterate that Amgen’s
`
`production was insufficient to provide Genentech with a complete understanding of Amgen’s
`
`trastuzumab manufacturing process.
`
`28.
`
`
`
`29.
`
`
`
`Amgen replied on February 1, 2018, with an additional supplemental production.
`
`On February 6, 2018, Genentech supplemented its § 262(l)(3)(A) list to include a
`
`newly issued manufacturing patent: U.S. Patent No. 9,868,760.
`
`30.
`
`
`
`On February 13, 2018, Amgen purported to provide its detailed statement
`
`concerning non-infringement and invalidity pursuant to 42 U.S.C. § 262(l)(3)(B) (“Amgen’s 3B
`
`Statement”). Amgen’s 3B Statement was deficient in numerous ways. For example, it—like
`
`Amgen’s document productions—failed to fully describe Amgen’s manufacturing process, such
`
`that Genentech was unable to evaluate many of Amgen’s non-infringement arguments.
`
`31.
`
`
`
`On
`
`,
`
`, and
`
`, Amgen produced
`
`additional documents regarding
`
`
`
`. These supplemental productions still failed to fully describe Amgen’s
`
`manufacturing process.
`
`32.
`
`
`
`On April 13, 2018, and subject to its objections, Genentech provided its response
`
`to Amgen’s 3C Statement pursuant to 42 U.S.C. § 262(l)(3)(C) (“Genentech’s 3C Statement”).
`
`Genentech included responses to Amgen’s non-infringement and invalidity statements for each
`
`of the patents addressed in Amgen’s 3B Statement and maintained that ABP 980 will infringe at
`
`ME1 27511836v.1
`
` 7 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 8 of 65 PageID #: 1522
`
`
`
`least 18 Genentech patents. With its 3C Statement, Genentech proposed that Amgen agree that
`
`all 18 of these patents be included in a first-phase infringement action under § 262(l)(6).
`
`33.
`
`
`
`On
`
`, and
`
`, Amgen produced additional documents
`
`regarding
`
`. These
`
`supplemental productions still failed to fully describe Amgen’s manufacturing process.
`
`34.
`
`
`
`After Genentech served its 3C Statement, the parties initiated negotiations under
`
`§ 262(l)(4). On May 23, 2018, Genentech and Amgen agreed that the 37 patents addressed in the
`
`exhibits to Genentech’s 3C Statement shall be the subject of an action for patent infringement
`
`under § 262(l)(6).
`
`35.
`
`
`
`In light of the parties’ agreement, § 262(l)(6)(A) required Genentech to bring an
`
`action for patent infringement with respect to each of the 37 patents that were part of the parties’
`
`agreement. This action is Genentech’s action pursuant to § 262(l)(6)(A).
`
`36.
`
`
`
`On
`
`
`
`, Amgen purported to notify Genentech pursuant to 42 U.S.C. § 262(l)(8)(A) that it
`
`intends to commence commercial marketing of ABP 980 in the United States no earlier than 180
`
`from
`
`(i.e.,
`
`).
`
`AMGEN’S aBLA PRODUCT
`
`37.
`
`
`
`Amgen has publicly stated that its aBLA product is biosimilar to Herceptin®. For
`
`example, Amgen has issued press releases claiming that ABP 980 is “a biosimilar candidate to
`
`Herceptin®” and “ABP 980 is a biosimilar candidate to trastuzumab,”4 and it has announced the
`
`
`4 http://www.amgen.com/media/news-releases/2017/07/amgen-and-allergan-submit-biosimilar-
`biologics-license-application-for-abp-980-to-us-food-and-drug-administration/
`
`ME1 27511836v.1
`
` 8 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 9 of 65 PageID #: 1523
`
`
`
`results of an Amgen study that purports to conclude that “[e]fficacy, safety and immunogenicity
`
`data support ABP 980 as a trastuzumab biosimilar.”5
`
`38.
`
`
`
`Given Amgen’s claim of biosimilarity, Amgen’s aBLA product must “utilize the
`
`same mechanism or mechanisms of action [as Herceptin®] for the condition or conditions of use
`
`prescribed, recommended, or suggested in the proposed labeling.” 42 U.S.C.
`
`§ 262(k)(2)(A)(i)(II).
`
`39.
`
`
`
`Under 35 U.S.C. § 271(e)(2)(C), Amgen has committed a statutory act of patent
`
`infringement with respect to patents identified by Genentech under 42 U.S.C. § 262(l)(3),
`
`through the submission of its aBLA application for ABP 980.
`
`GENENTECH’S ASSERTED PATENTS
`
`40.
`
`
`
`Genentech has spent over two decades and significant resources developing
`
`Herceptin®, and the USPTO has awarded to Genentech numerous patents on innovations
`
`resulting from this massive undertaking. These patents cover the antibody trastuzumab, along
`
`with its manufacture and use.
`
`41.
`
`
`
`Through the parties’ exchange of information pursuant to the BPCIA, Genentech
`
`identified the following patents for which Genentech reasonably believed that it could assert a
`
`claim of infringement with respect to ABP 980, based upon the information that Genentech had
`
`available to it at the time: U.S. Patent No. 6,331,415, U.S. Patent No. 7,923,221, U.S. Patent No.
`
`6,407,213, U.S. Patent No. 7,846,441, U.S. Patent No. 7,892,549, U.S. Patent No. 6,627,196,
`
`U.S. Patent No. 7,371,379, U.S. Patent No. 6,417,335, U.S. Patent No. 6,489,447, U.S. Patent
`
`No. 9,249,218, U.S. Patent No. 8,574,869, U.S. Patent No. 6,620,918, U.S. Patent No. 8,691,232,
`
`
`5 https://www.amgen.com/media/news-releases/2017/09/amgen-and-allergan-present-phase-3-
`data-on-biosimilar-trastuzumab-candidate-abp-980-at-the-european-society-for-medical-
`oncology-2017-congress/
`
`ME1 27511836v.1
`
` 9 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 10 of 65 PageID #: 1524
`
`
`
`U.S. Patent No. 8,771,988, U.S. Patent No. 9,428,766, U.S. Patent No. 9,487,809, U.S. Patent
`
`No. 7,449,184, U.S. Patent No. 7,501,122, U.S. Patent No. 7,993,834, U.S. Patent 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, U.S. Patent
`
`No. 6,121,428, U.S. Patent No. 6,242,177, U.S. Patent No. 6,586,206, U.S. Patent No. 8,044,017,
`
`U.S. Patent No. 8,710,196, U.S. Patent No. 9,493,744, U.S. Patent No. 6,870,034, U.S. Patent
`
`No. 8,357,301, U.S. Patent No. 9,047,438, U.S. Patent No. 9,080,183, U.S. Patent No. 8,314,225,
`
`U.S. Patent No. 8,512,983, U.S. Patent No. 9,714,293, and U.S. Patent No. 9,868,760.
`
`The Cabilly Patents
`
`42.
`
`
`
`U.S. Patent Nos. 6,331,415 and 7,923,221 (collectively, the “Cabilly Patents”)
`
`describe and claim a process for producing monoclonal antibodies, such as Herceptin®, from
`
`recombinant DNA. This effective and efficient process applies a novel co-expression technique
`
`to produce antibody heavy and light chains in a single host cell, and has given rise to an entire
`
`industry of therapeutic monoclonal antibodies.
`
`43.
`
`
`
`U.S. Patent No. 6,331,415 (“the ’415 patent”), titled “Methods of Producing
`
`Immunoglobulins, Vectors and Transformed Host Cells for Use Therein,” was duly and legally
`
`issued by the Patent Office on December 18, 2001. A true and correct copy of the ’415 patent is
`
`attached as Exhibit A. Genentech and the City of Hope are the owners by assignment of the ’415
`
`patent.
`
`44.
`
`
`
`U.S. Patent No. 7,923,221 (“the ’221 patent”), titled “Methods of Making
`
`Antibody Heavy and Light Chains Having Specificity for a Desired Antigen,” was duly and
`
`legally issued by the Patent Office on April 12, 2011. A true and correct copy of the ’221 patent
`
`is attached as Exhibit B. Genentech and the City of Hope are the owners by assignment of the
`
`’221 patent.
`
`ME1 27511836v.1
`
` 10 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 11 of 65 PageID #: 1525
`
`
`
`The ’213 Patent
`
`45.
`
`
`
`U.S. Patent No. 6,407,213 (“the ’213 patent”) claims the Herceptin® antibody
`
`itself, along with other humanized monoclonal antibodies. The inventors of the ’213 patent
`
`discovered that by grafting the key parts of a mouse antibody onto a human antibody consensus
`
`sequence, they could create antibodies that were both tolerated by the immune system and
`
`effective to treat diseases like HER2-positive breast cancer. The techniques described in the
`
`’213 patent allowed scientists to efficiently design antibodies for specific disease targets by
`
`modifying mouse antibodies produced in the laboratory in specific ways so that they are
`
`compatible with a human immune system.
`
`46.
`
`
`
`The ’213 patent, titled “Method for Making Humanized Antibodies,” was duly
`
`and legally issued by the Patent Office on June 18, 2002. A true and correct copy of the ’213
`
`patent is attached as Exhibit C. Genentech is the owner by assignment of the ’213 patent.
`
`The Combination Chemotherapy Patents
`
`47.
`
`
`
`U.S. Patent No. 7,846,441 (“the ’441 patent”), claims the administration of
`
`Herceptin® in combination with a chemotherapy agent known as a taxoid, in the absence of an
`
`anthracycline derivative (another chemotherapy agent) in an amount effective to extend time to
`
`disease progression without overall increase in severe adverse events. This specific method of
`
`treatment unexpectedly resulted in a significant improvement in patient outcomes. It nearly
`
`doubled the time until disease progression compared to treatment using a taxoid alone, and it also
`
`avoided the serious cardiotoxicity associated with Herceptin® in combination with anthracycline
`
`derivatives that unexpectedly presented during the Herceptin® clinical trials.
`
`ME1 27511836v.1
`
` 11 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 12 of 65 PageID #: 1526
`
`
`
`48.
`
`
`
`The ’441 patent, titled “Treatment with Anti-ErbB2 Antibodies,” was duly and
`
`legally issued by the Patent Office on December 7, 2010. A true and correct copy of the ’441
`
`patent is attached as Exhibit D. Genentech is the owner by assignment of the ’441 patent.
`
`49.
`
`
`
`U.S. Patent No. 7,892,549 (“the ’549 patent”) is a continuation to the ’441 patent
`
`that claims a method of treating a patient with HER2-positive breast cancer by administering
`
`Herceptin® in combination with a taxoid and a further growth inhibitory agent or further
`
`therapeutic agent.
`
`50.
`
`
`
`The ’549 patent, titled “Treatment with Anti-ErbB2 Antibodies,” was duly and
`
`legally issued by the Patent Office on February 22, 2011. A true and correct copy of the ’549
`
`patent is attached as Exhibit E. Genentech is the owner by assignment of the ’549 patent.
`
`51.
`
`
`
`U.S. Patent No. 8,425,908 (“the ’908 patent”), claims priority to the same
`
`provisional application as the ’441 and ’549 patents. The ’908 patent claims a method of treating
`
`a patient with HER2-positive gastric cancer by administering Herceptin® in combination with
`
`chemotherapy and in the absence of an anthracycline derivative.
`
`52.
`
`
`
`The ’908 patent, titled “Treatment with Anti-ErbB2 Antibodies,” was duly and
`
`legally issued by the Patent Office on April 23, 2013. A true and correct copy of the ’908 patent
`
`is attached as Exhibit F. Genentech is the owner by assignment of the ’908 patent.
`
`The Method of Administration Patents
`
`53.
`
`
`
`U.S. Patent Nos. 6,627,196 and 7,371,379 (collectively, the “Method of
`
`Administration Patents”) generally cover the most common administration method for
`
`Herceptin®: an initial dose of 8 mg/kg, followed by 6 mg/kg doses once every three weeks.
`
`Herceptin® was initially approved for administration on a weekly regimen, but Genentech
`
`discovered that the drug could be dosed only once every three weeks without reducing safety or
`
`ME1 27511836v.1
`
` 12 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 13 of 65 PageID #: 1527
`
`
`
`effectiveness. The discovery of three-weekly dosing has had a marked impact on patients’
`
`quality of life by providing the same life-saving effects of Herceptin® while allowing patients to
`
`receive treatment less frequently.
`
`54.
`
`
`
`U.S. Patent No. 6,627,196 (“the Baughman ’196 patent”), titled “Dosages for
`
`Treatment with Anti-ErbB2 Antibodies,” was duly and legally issued by the Patent Office on
`
`September 30, 2003. A true and correct copy of the Baughman ’196 patent is attached as Exhibit
`
`G. Genentech is the owner by assignment of the Baughman ’196 patent.
`
`55.
`
`
`
`U.S. Patent No. 7,371,379 (“the ’379 patent”), titled “Dosages for Treatment with
`
`Anti-ErbB2 Antibodies,” was duly and legally issued by the Patent Office on May 13, 2008. A
`
`true and correct copy of the ’379 patent is attached as Exhibit H. Genentech is the owner by
`
`assignment of the ’379 patent.
`
`The Acidic Variants Patents
`
`56.
`
`
`
`U.S. Patent Nos. 6,417,335, 6,489,447, and 9,249,218 (collectively, the “Acidic
`
`Variants Patents”) cover compositions with reduced amounts of more acidic structural variants of
`
`trastuzumab (“acidic variants”) and chromatographic processes for removing these acidic
`
`variants during purification. Some trastuzumab acidic variants have lower potency than
`
`trastuzumab itself. The Acidic Variants Patents describe and claim chromatographic processes
`
`and compositions that ensure the Herceptin® drug product is uniformly pure and effective.
`
`57.
`
`
`
`U.S. Patent No. 6,417,335 (“the ’335 patent”), titled “Protein Purification,” was
`
`duly and legally issued by the Patent Office on July 9, 2002. A true and correct copy of the ’335
`
`patent is attached as Exhibit I. Genentech is the owner by assignment of the ’335 patent.
`
`58.
`
`
`
`U.S. Patent No. 6,489,447 (“the ’447 patent”), titled “Protein Purification,” was
`
`duly and legally issued by the Patent Office on December 3, 2002. A true and correct copy of
`
`ME1 27511836v.1
`
` 13 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 14 of 65 PageID #: 1528
`
`
`
`the ’447 patent is attached as Exhibit J. Genentech is the owner by assignment of the ’447
`
`patent.
`
`59.
`
`
`
`U.S. Patent No. 9,249,218 (“the ’218 patent”), titled “Protein Purification,” was
`
`duly and legally issued by the Patent Office on February 2, 2016. A true and correct copy of the
`
`’218 patent is attached as Exhibit K. Genentech is the owner by assignment of the ’218 patent.
`
`Combination Therapy with Perjeta
`
`60.
`
`
`
`U.S. Patent Nos. 7,501,122, 7,449,184, and 8,691,232 claim novel therapies
`
`combining trastuzumab with another anti-HER2 antibody developed by Genentech called
`
`pertuzumab. That combination therapy is a common method of treatment for HER2-positive
`
`breast cancer patients involving Herceptin®.
`
`61.
`
`
`
`U.S. Patent No. 7,501,122 (“the ’122 patent”), titled “Treatment with Anti-ErbB2
`
`Antibody Combinations,” was duly and legally issued by the Patent Office on March 10, 2009.
`
`A true and correct copy of the ’122 patent is attached as Exhibit L. Genentech is the owner by
`
`assignment of the ’122 patent.
`
`62.
`
`
`
`U.S. Patent No. 7,449,184 (“the ’184 patent”), titled “Fixed Dosing of HER
`
`Antibodies,” was duly and legally issued by the Patent Office on November 11, 2008. A true
`
`and correct copy of the ’184 patent is attached as Exhibit M. Genentech is the owner by
`
`assignment of the ’184 patent.
`
`63.
`
`
`
`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 N. Genentech is
`
`the owner by assignment of the ’232 patent.
`
`ME1 27511836v.1
`
` 14 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 15 of 65 PageID #: 1529
`
`
`
`HER2 Diagnostic Patents
`
`64.
`
`
`
`U.S. Patent Nos. 7,993,834, 8,076,066, and 8,440,402 claim novel techniques for
`
`identifying patients who might benefit from trastuzumab therapy using gene amplification
`
`techniques even where immunohistochemistry techniques suggest that the patient may not
`
`overexpress HER2.
`
`65.
`
`
`
`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 O. Genentech is the owner by assignment
`
`of the ’834 patent.
`
`66.
`
`
`
`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
`
`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 P. Genentech is the owner by assignment of the ’066
`
`patent.
`
`67.
`
`
`
`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 Q. Genentech is the owner by assignment of the ’402 patent.
`
`Cell Culture, Purification, and Antibody Manufacturing Patents
`
`68.
`
`
`
`U.S. Patent Nos. 6,121,428, 6,242,177, 6,586,206, 6,620,918, 6,870,034,
`
`8,044,017, 8,314,225, 8,357,301, 8,460,895, 8,512,983, 8,574,869, 8,710,196, 8,771,988,
`
`9,047,438, 9,080,183, 9,428,766, 9,487,809, 9,493,744, 9,714,293, and 9,868,760 claim novel
`
`ME1 27511836v.1
`
` 15 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 16 of 65 PageID #: 1530
`
`
`
`techniques developed by Genentech relating to various aspects of cell culture, purification, and
`
`antibody purification.
`
`69.
`
`
`
`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 R. Genentech is the owner by assignment of the ’428
`
`patent.
`
`70.
`
`
`
`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 S. Genentech is
`
`the owner by assignment of the ’177 patent.
`
`71.
`
`
`
`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 T.
`
`Genentech is the owner by assignment of the ’206 patent.
`
`72.
`
`
`
`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 U. Genentech is the owner by
`
`assignment of the ’918 patent.
`
`73.
`
`
`
`U.S. Patent No. 6,870,034 (“the ’034 patent”), titled “Protein Purification,” was
`
`duly and legally issued by the Patent Office on March 22, 2005. A true and correct copy of the
`
`’034 patent is attached as Exhibit V. Genentech is the owner by assignment of the ’034 patent.
`
`ME1 27511836v.1
`
` 16 -
`
`
`
`-
`

`

`Case 1:18-cv-00924-CFC-SRF Document 10 Filed 07/02/18 Page 17 of 65 PageID #: 1531
`
`
`
`74.
`
`
`
`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.
`
`75.
`
`
`
`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
`
`X. The ’225 patent is assigned to Hoffmann-La Roche Inc. (“HLR”), and Genentech is the
`
`exclusive licensee with the right to enforce the ’225 patent.
`
`76.
`
`
`
`U.S. Patent No. 8,357,301 (“the ’301 patent”), titled “Chromatography Equipment
`
`Characterization,” was duly and legally issued by the Patent Office on January 22, 2013. A true
`
`and correct copy of the ’301 patent is attached as Exhibit Y. The ’301 patent is assigned to HLR,
`
`and Genentech is the exclusive licensee with the right to enforce the ’301 patent.
`
`77.
`
`
`
`U.S. Patent No. 8,460,895 (“the ’895 patent”), titled “Method for Producing
`
`Recombinant Proteins with a Constant Content of pCO2 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 Z. The ’895 patent is assigned to HLR, and Genentech is the exclusive
`
`licensee with the sole right to enforce the ’895 patent.
`
`78.
`
`
`
`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 attach