Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 1 of 79 PageID #: 1
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`
`GENENTECH, INC., CITY OF HOPE, and
`HOFFMANN-LA ROCHE INC.,
`
`
`
`
`
`CELLTRION, INC., CELLTRION
`HEALTHCARE, CO. LTD., TEVA
`PHARMACEUTICALS USA, INC., and
`TEVA PHARMACEUTICALS
`INTERNATIONAL GMBH,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`C.A. No.
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`
`
`
`
`
`
`Plaintiffs,
`
`
`
`v.
`
`
`
`Defendants.
`
`COMPLAINT
`
`Plaintiffs Genentech, Inc. (“Genentech”), City of Hope, and Hoffmann-La Roche Inc.
`
`(“HLR”; collectively, “Plaintiffs”) bring this Complaint for declaratory and injunctive relief
`
`against Defendants Celltrion, Inc. and Celltrion Healthcare Co., Ltd. (collectively, “Celltrion”)
`
`and Defendants Teva Pharmaceuticals USA, Inc. and Teva Pharmaceuticals International GmbH
`
`(collectively, “Teva”) to address Defendants’ infringement of 40 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
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 2 of 79 PageID #: 2
`
`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
`
`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
`
`1
`Gina Kolata and Lawrence M. Fisher, Drugs to Fight Breast Cancer Near Approval,
`NEW YORK TIMES (FRONT PAGE) (Sept. 3, 1998).
`Robert Langreth, Breast-Cancer Drug Is Backed by FDA Panel, Wall Street J. (Sept. 3,
`1998).
`
`2
`
`– 2 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 3 of 79 PageID #: 3
`
`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.
`
`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, Celltrion is seeking
`
`FDA approval of a biosimilar version of Herceptin® called CT-P6. CT-P6 is a copycat product
`
`for which Celltrion is seeking the same label indications and usage as Herceptin®. In fact,
`
`Celltrion is relying upon Genentech’s own studies demonstrating the safety and efficacy of
`
`Herceptin® to obtain approval of its biosimilar product. Upon information and belief, Teva will
`
`be engaged in the marketing and distribution of Celltrion’s CT-P6 product in the United States
`
`upon FDA approval.
`
`8.
`
`
`
`In 2010, Congress provided a pathway for resolving patent disputes relating to
`
`biosimilar products through the Biologics Price Competition and Innovation Act (“BPCIA”).
`
`Celltrion 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). However, before completing the process required by
`
`the statute, Celltrion has purported to provide Genentech with a notice pursuant to 42 U.S.C.
`
`§ 262(l)(8)(A) that they intend to market CT-P6 in the United States. That notice of commercial
`
`– 3 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 4 of 79 PageID #: 4
`
`marketing allows Plaintiffs to bring an immediate action for injunctive and declaratory relief
`
`concerning the patents that would be infringed by the manufacture and sale of Celltrion’s
`
`biosimilar product.
`
`9.
`
`
`
`Plaintiffs thus bring this action for infringement pursuant to 35 U.S.C. § 271(e)(2)
`
`based upon Celltrion’s submission of its aBLA for CT-P6. 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 Celltrion’s biosimilar product would infringe
`
`the 40 patents described below. Pursuant to 42 U.S.C. § 262(l)(8)(B), Plaintiffs also seek a
`
`preliminary and/or permanent injunction barring Defendants’ manufacture, use, offer to sell,
`
`sale, or importation of its biosimilar product prior to the expiration of those patents. In the event
`
`that Defendants import or launch their biosimilar product and/or otherwise practice 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
`
`– 4 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 5 of 79 PageID #: 5
`
`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.
`
`
`
`Plaintiff Hoffmann La-Roche Inc. is a corporation organized and existing under
`
`the laws of the State of New Jersey with its principal place of business at 150 Clove Road, Suite
`
`8, Little Falls, New Jersey 07424.
`
`
`
` 15.
`
`Upon information and belief, Defendant Celltrion, Inc. is a company organized
`
`and existing under the laws of the Republic of Korea with its principal place of business located
`
`at 19, Academy-ro, 51beon-gil, Yeonsu-gu, Incheon, Korea.
`
`16.
`
`
`
`Celltrion, Inc. is, among other things, engaged in the development of biologic
`
`drugs, including a proposed biosimilar version of Genentech’s Herceptin® product, CT-P6
`
`(“Celltrion’s aBLA product”). Upon information and belief, Celltrion’s aBLA product will be
`
`distributed and sold in the State of Delaware and throughout the United States.
`
`17.
`
`
`
`Upon information and belief, Defendant Celltrion Healthcare Co., Ltd. is a
`
`company organized and existing under the laws of the Republic of Korea with its principal place
`
`of business located at 19, Academy-ro, 51beon-gil, Yeonsu-gu, Incheon, Korea.
`
`18.
`
`
`
`Celltrion Healthcare Co., Ltd. is, among other things, engaged in the marketing
`
`and distribution of Celltrion’s biologic products in the United States, including Celltrion’s aBLA
`
`product.
`
`– 5 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 6 of 79 PageID #: 6
`
`19.
`
`
`
`Upon information and belief, Defendant Teva Pharmaceuticals USA, Inc. is a
`
`company organized and existing under the laws of the State of Delaware with its principal place
`
`of business located at 1090 Horsham Road, North Wales, PA 19454.
`
`20.
`
`
`
`Upon information and belief, Defendant Teva Pharmaceuticals International
`
`GmbH is a company organized and existing under the laws of Switzerland with its principal
`
`place of business located at Schlüsselstrasse 12, Jona (SG) 8645, Switzerland.
`
`21.
`
`
`
`Upon information and belief, Celltrion, Inc., Celltrion Healthcare Co., Ltd., and
`
`Teva Pharmaceuticals International GmbH have entered into an exclusive partnership to
`
`commercialize Celltrion’s aBLA product in the United States. Upon information and belief,
`
`Teva Pharmaceuticals USA, Inc. will market and distribute Celltrion’s aBLA product in the
`
`United States upon FDA approval.
`
`JURISDICTION AND VENUE
`
`22.
`
`
`
`This action arises under the BPCIA, 42 U.S.C. § 262(l), 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.
`
`
`
` 23.
`
`Venue is proper with respect to Celltrion, Inc., a Korean company, pursuant to 28
`
`U.S.C. § 1391(c)(3).
`
`
`
` 24.
`
`Venue is proper with respect to Celltrion Healthcare Co., Ltd., a Korean
`
`company, pursuant to 28 U.S.C. § 1391(c)(3).
`
`25.
`
`
`
`Venue is proper with respect to Teva Pharmaceuticals USA, Inc. in this Court
`
`pursuant to 28 U.S.C. § 1400(b) because Teva Pharmaceuticals USA, Inc. is incorporated in
`
`Delaware.
`
`– 6 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 7 of 79 PageID #: 7
`
`26.
`
`
`
`Venue is proper with respect to Teva Pharmaceuticals International GmbH, a
`
`Swiss company, pursuant to 28 U.S.C. § 1391(c)(3).
`
`
`
` 27.
`
`This Court has personal jurisdiction over the Celltrion Defendants because they
`
`have filed an Abbreviated Biologics License Application (“aBLA”) No. 761091 with the FDA
`
`seeking approval to market its aBLA product, which reliably indicates that they, together with
`
`the Teva Defendants, will market their proposed biosimilar product in Delaware if approved.
`
`Alternatively, this Court has personal jurisdiction over the Celltrion Defendants pursuant to
`
`Federal Rule of Civil Procedure 4(k)(2).
`
`28.
`
`
`
`This Court has personal jurisdiction over Teva Pharmaceuticals USA, Inc.
`
`because it is a Delaware corporation and, upon information and belief, because it will be
`
`involved in the marketing and distribution of Celltrion’s aBLA product upon FDA approval.
`
`29.
`
`
`
`This Court has personal jurisdiction over Teva Pharmaceuticals International
`
`GmbH because, upon information and belief, it has entered into an exclusive partnership with the
`
`Celltrion Defendants to commercialize the Celltrion aBLA product in the United States, which
`
`reliably indicates that it will market the Celltrion aBLA product in Delaware if approved.
`
`Alternatively, this Court has personal jurisdiction over Teva Pharmaceutical International GmbH
`
`pursuant to Federal Rule of Civil Procedure 4(k)(2).
`
`THE PARTIES’ EXCHANGES UNDER THE BPCIA
`
`30.
`
`
`
`On July 31, 2017, Celltrion announced that the FDA had accepted its aBLA for
`
`review.
`
`31.
`
`
`
`On August 1, 2017, Genentech sent a letter to Celltrion’s outside counsel
`
`requesting that they provide a copy of the aBLA and certain information concerning the
`
`manufacture of CT-P6 pursuant to 42 U.S.C. § 262(l)(2).
`
`– 7 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 8 of 79 PageID #: 8
`
`32.
`
`
`
` Celltrion responded on August 9, 2017 without providing any manufacturing
`
`information. Genentech responded on September 19, 2017 to reiterate its request for specific
`
`information concerning the manufacture of Celltrion’s biosimilar product, and explained why the
`
`missing information was necessary to evaluate whether Celltrion’s proposed product infringes
`
`specific Genentech patents. Celltrion provided some manufacturing information on September
`
`25, 2017, but did not satisfy their disclosure obligations. On October 9, 2017, Celltrion refused
`
`to provide the sought-after manufacturing information, in contravention of 42 U.S.C. § 262(l)(2).
`
`Despite Celltrion’s non-compliance (and without waiving Genentech’s objection to such non-
`
`compliance), Genentech provided its operative list of patents pursuant to 42 U.S.C. §
`
`262(l)(3)(A) on October 10, 2017 (“Genentech’s 3A List”).
`
`33.
`
`
`
`On November 7, 2017, Celltrion purported to provide its detailed statement
`
`concerning non-infringement and invalidity pursuant to 42 U.S.C. § 262(l)(3)(B) for 38 of the 40
`
`patents on Genentech’s 3A List (“Celltrion’s 3B Statement”). Celltrion’s 3B Statement was
`
`deficient in numerous ways. For example, it—like Celltrion’s document production—failed to
`
`fully describe Celltrion’s manufacturing process, such that Genentech was unable to evaluate
`
`many of Celltrion’s non-infringement arguments.
`
`34.
`
`
`
`Nonetheless, and subject to its objections, Genentech provided its response to
`
`Celltrion’s 3B Statement on January 5, 2018, pursuant to 42 U.S.C. § 262(l)(3)(B) (“Genentech’s
`
`3C Statement”). Genentech included responses to Celltrion’s non-infringement and invalidity
`
`statements for 18 of the 38 patents addressed in Celltrion’s 3B Statement. With its 3C
`
`Statement, Genentech proposed that Celltrion agree that all patents addressed in Genentech’s 3C
`
`Statement be included in an infringement action under § 262(l)(6).
`
`– 8 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 9 of 79 PageID #: 9
`
`35.
`
`
`
`Celltrion wrote to Genentech on January 11, 2018, indicating that it wished to
`
`litigate all of the patents on Genentech’s (3)(A) list. But, rather than “engage in good faith
`
`negotiations” on which patents to litigate as required by 42 U.S.C. § 262(l)(4), Celltrion then
`
`immediately sought a declaratory
`
`judgment of non-infringement,
`
`invalidity, and/or
`
`unenforceability for all 38 patents addressed in its 3B Statement in the U.S. District Court for the
`
`Northern District of California on January 11, 2018. See Complaint (ECF No. 1), Celltrion, Inc.
`
`v. Genentech, Inc., No. 3:18-cv-00274 (N.D. Cal. filed Jan. 11, 2018). Celltrion also purported
`
`to provide Genentech with a notice of commercial marketing for its proposed trastuzumab
`
`biosimilar pursuant to 42 U.S.C. § 262(l)(8)(A).3 See id. ¶ 16.
`
`CELLTRION’S aBLA PRODUCT
`
`36.
`
`
`
`Celltrion’s public statements demonstrate that its aBLA product is biosimilar to
`
`Herceptin®. For example, Celltrion has issued press releases claiming that CT-P6 is “a
`
`biosimilar to Herceptin (trastuzumab),” 4 “the Herceptin biosimilar,” 5 and that “[i]ts original
`
`product is Herceptin.”6
`
`37.
`
`
`
`Given Celltrion’s claim of biosimilarity, Celltrion’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).
`
`
`3
`Celltrion has taken the position that the exact date of its notice of commercial marketing
`is confidential.
`See https://www.celltrion.com/en/pr/reportDetail.do?seq=436.
`See https://www.celltrion.com/en/pr/reportDetail.do?seq=403.
`See https://www.celltrion.com/en/pr/reportDetail.do?seq=422.
`
`4
`5
`6
`
`– 9 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 10 of 79 PageID #: 10
`
`38.
`
`
`
`Under 35 U.S.C. § 271(e)(2)(C), Celltrion 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 CT-P6.
`
`GENENTECH’S ASSERTED PATENTS
`
`39.
`
`
`
`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.
`
`40.
`
`
`
`Upon information and belief, Celltrion’s aBLA product will infringe at least the
`
`following patents, for which Genentech provided claim-by-claim infringement contentions in its
`
`3C Statement and which Genentech has asserted in this lawsuit: 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. 6,339,142;
`
`U.S. Patent No. 6,417,335; 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. 7,485,704; U.S. Patent No. 7,807,799; U.S. Patent No.
`
`7,993,834; U.S. Patent No. 8,076,066; U.S. Patent No. 8,425,908; and U.S. Patent No.
`
`8,440,402.
`
`
`
` 41.
`
`Further, upon information and belief, Celltrion’s aBLA product will infringe at
`
`least the following patents, which Genentech included on its 3A List and which Genentech has
`
`asserted in this lawsuit: U.S. Patent No. 6,242,177 and U.S. Patent No. 6,121,428. Celltrion’s
`
`3B Statement did not dispute that the manufacturing process for its aBLA product practices the
`
`method claims in these patents.
`
`42.
`
`
`
`Based on Defendants’ complaint in Celltrion, Inc. v. Genentech, Inc., No. 3:18-
`
`cv-00274 (N.D. Cal. filed Jan. 11, 2018), there is also an active controversy about whether
`
`– 10 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 11 of 79 PageID #: 11
`
`Celltrion’s aBLA product will infringe the following patents, which Genentech included on its
`
`3A List and which Genentech has asserted in this lawsuit: U.S. Patent No. 6,489,447; U.S.
`
`Patent 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; U.S. Patent No. 7,449,184; U.S. Patent No. 7,501,122; U.S. Patent No. 8,357,301;
`
`U.S. Patent No. 8,460,895; U.S. Patent No. 8,512,983; U.S. Patent No. 8,633,302; U.S. Patent
`
`No. 8,691,232; U.S. Patent No. 8,771,988; U.S. Patent No. 8,822,655; U.S. Patent No.
`
`9,047,438; U.S. Patent No. 9,080,183; U.S. Patent No. 9,428,548; U.S. Patent No. 9,428,766;
`
`U.S. Patent No. 9,487,809; and U.S. Patent No. 9,714,293.
`
`The Cabilly Patents
`
`43.
`
`
`
`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.
`
`44.
`
`
`
`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.
`
`45.
`
`
`
`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.
`
`– 11 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 12 of 79 PageID #: 12
`
`The ’213 Patent
`U.S. Patent No. 6,407,213 (“the ’213 patent”) claims the Herceptin® antibody
`
`46.
`
`
`
`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.
`
`47.
`
`
`
`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
`
`
`
` 48.
`
`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.
`
`49.
`
`
`
`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.
`
`– 12 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 13 of 79 PageID #: 13
`
`50.
`
`
`
`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.
`
`51.
`
`
`
`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.
`
`52.
`
`
`
`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.
`
`53.
`
`
`
`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
`
`54.
`
`
`
`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
`
`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.
`
`– 13 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 14 of 79 PageID #: 14
`
`
`
` 55.
`
`U.S. Patent No. 6,627,196 (“the’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’196 patent is attached as Exhibit G. Genentech is the
`
`owner by assignment of the’196 patent.
`
`56.
`
`
`
`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
`
`57.
`
`
`
`U.S. Patent Nos. 6,339,142, 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.
`
`58.
`
`
`
`U.S. Patent No. 6,339,142 (“the ’142 patent”), titled “Protein Purification,” was
`
`duly and legally issued by the Patent Office on January 15, 2002. A true and correct copy of the
`
`’142 patent is attached as Exhibit I. Genentech is the owner by assignment of the ’142 patent.
`
`59.
`
`
`
`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 J. Genentech is the owner by assignment of the ’335 patent.
`
`60.
`
`
`
`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
`
`– 14 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 15 of 79 PageID #: 15
`
`the ’447 patent is attached as Exhibit K. Genentech is the owner by assignment of the ’447
`
`patent.
`
`
`
` 61.
`
`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 L. Genentech is the owner by assignment of the ’218 patent.
`
`Combination Therapy with Perjeta
`
`
`
` 62.
`
`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®.
`
`63.
`
`
`
`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 M. Genentech is the owner by
`
`assignment of the ’122 patent.
`
`64.
`
`
`
`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 N. Genentech is the owner by
`
`assignment of the ’184 patent.
`
`65.
`
`
`
`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 O. Genentech is
`
`the owner by assignment of the ’232 patent.
`
`– 15 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 16 of 79 PageID #: 16
`
`HER2 Diagnostic Patents
`
`66.
`
`
`
`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.
`
`67.
`
`
`
`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 P. Genentech is the owner by assignment
`
`of the ’834 patent.
`
`68.
`
`
`
`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 Q. Genentech is the owner by assignment of the ’066
`
`patent.
`
`69.
`
`
`
`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 R. Genentech is the owner by assignment of the ’402 patent.
`
`Cell Culture, Purification, and Antibody Manufacturing Patents
`
`70.
`
`
`
`U.S. Patent Nos. 6,586,206, 6,610,516, 6,716,602, 7,390,660, 8,460,895,
`
`8,512,983, 8,574,869, 8,771,988, 9,080,183, 9,428,766, 9,487,809, 9,714,293, 6,417,335,
`
`6,489,447, 6,620,918, 7,485,704, 7,807,799, 8,357,301, 8,633,302, 8,822,655, 9,047,438,
`
`– 16 –
`
`

`

`Case 1:18-cv-00095-GMS Document 1 Filed 01/12/18 Page 17 of 79 PageID #: 17
`
`9,428,548 claim novel techniques developed by Genentech relating to various aspects of cell
`
`culture, purification, and antibody purification.
`
`71.
`
`
`
`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 S. Genentech is the owner by
`
`assignment of the ’918 patent.
`
`72.
`
`
`
`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 T.
`
`Genentech is the owner by assignment of the ’704 patent.
`
`73.
`
`
`
`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 U.
`
`Genentech is the owner by assignment of the ’799 patent.
`
`74.
`
`
`
`U.S. Patent No. 9,428,548 (“the ’548 patent”),