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`Lloyd R. Day, Jr., State Bar No. 90875
`DayL@howrey.com
`2 Robert M. Galvin, State Bar No. 171508
`GalvinR@howrey.com
`Jackie N. Nakamura, State Bar No. 148531
`N akamuraJ @howrey.com
`4 HOWREY LLP
`1950 University A venue, 41h Floor
`5 East Palo Alto, CA 94303
`Telephone: (650) 798-3500
`6 Facsimile: (650) 798-3600
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`Attorneys for Plaintiffs
`GLAXO GROUP LIMITED and
`GLAXOSMITHKLJNE LLC
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`UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF CALIFORNIA
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`JSW
`675 ··~
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`SAN F"''CO!UION
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`GLAXO GROUP LIMITED and
`GLAXOSMITHKLINE LLC,
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`Case No.:
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`Plaintiffs,
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`VS.
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`COMPLAINT FOR DECLARATORY
`JUDGMENT OF INVALIDITY,
`UNENFORCEABILITY, AND
`NONINFRING EMENT
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`GENENTECH, INC., and CITY OF HOPE,
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`Defendants.
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`/
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`Plaintiffs Glaxo Group Limited and GlaxoSmithKiine LLC (collectively, "GSK"), for their
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`]9 Complaint against Genentech, Inc. and City of Hope (collectively, "Defendants"), allege as follows:
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`l.
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`GSK seeks a declaration that U.S. Patent 6,331 ,415 titled "Methods of Producing
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`NATURE OF THE CASE
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`Immunoglobulins, Vectors and Transfonned Host Cells for Use Therein" (the "Cabilly II patent"
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`attached as Exhibit A), including the Ex Parte Reexamination Certificate issued pursuant to
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`24 Reexamination Nos. 90/007,542 and 90/007,859 (attached as Exhibit B), is invalid, unenforceable,
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`and not infringed by the manufacture, use, sale, offer to sell, or importation of GSK's ofatumumab
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`(Arzerra™) antibody product.
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`2.
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`GSK recently began marketing and selling Arzerra™ in the United States for the
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`treatment of patients whose chronic lymphocytic leukemia ("CLL") is refractory to previous
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`DM_US:23108491_1
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1178
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`Merck Ex. 1051, pg 1204
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`

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`ca e 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 2 of 17 Page ID #:2
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`therapies (fludarabine and alemtuzumab). GSK brings this action to lift the cloud created by the
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`imminent threat of Defendants' enforcement of the Cabilly II patent against GSK. Without
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`declaratory relief, the threat of enforcement of the Cab illy II patent poses a substantial risk of injury
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`to GSK as well as the patients, nurses, and doctors now using Arzerra™ for treatment. The
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`continued existence and enforcement of this invalid and unenforceable patent impedes not only the
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`development and sale of Arzerra™, but also the development and sale of other life-saving
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`recombinant antibody products.
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`3.
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`Defendants have asserted that the Cabilly II patent broadly covers the use of certain
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`9 well-known, conventional recombinant methods to produce any antibody product in any type of host
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`cell. Defendants have filed infringement claims under the Cabilly II patent against companies who
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`have made and sold antibody products that were produced using recombinant methods similar to the
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`recombinant methods used by GSK to make Arzerra™. Defendant Genentech, Inc. has specifically
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`identified GSK's Arzerra™ antibody product as a potential competitor to one of Genentech's own
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`products, and has stated that it expects to be involved in future litigation relating to the enforcement
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`15 of the Cabilly II patent. During GSK's dealings with Genentech, Genentech has repeatedly taken the
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`position that GSK requires a license under the Cabilly II patent to make and sell a variety of different
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`antibody products, including products produced by the same or similar process as Arzerra™. As
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`recently as the Fall of 2008, after GSK acquired rights to Arzerra™, counsel for Genentech inquired
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`19 what GSK would do about the Cabilly II patent. Given Defendants' past acts and statements and
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`20 GSK's sale of Arzerra™ in the United States, a real, immediate, and substantial dispute exists
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`between the parties concerning the Cabilly II patent for which GSK now seeks declaratory relief.
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`4.
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`PlaintiffGiaxo Group Limited d/b/a GlaxoSmithKline is an English corporation
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`THE PARTIES
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`having a principal place of business at Glaxo Wellcome House, Berkley Avenue, Greenford,
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`25 Middlesex, UB6 ONN, United Kingdom.
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`5.
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`PlaintiffGlaxoSmithKline LLC is a Delaware limited liability company having a
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`principal place of business at One Franklin Plaza, Philadelphia, Pennsylvania, 19102.
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`DM_US 231084YI_I
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`2
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1179
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`Merck Ex. 1051, pg 1205
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`

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`ca e 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 3 of 17 Page ID #:3
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`6.
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`Defendant Genentech, Inc. ("Genentech") is a Delaware corporation having its
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`principal place of business in South San Francisco, California.
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`7.
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`City of Hope is a California not-for-profit organization having its principal place of
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`business in Duarte, California. On infonnation and belief, City of Hope has a place of business in
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`this District at 55 Hawthorne Street, Suite 450, San Francisco, California, 94105.
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`8.
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`On infonnation and belief, Genentech and City of Hope are co-assignees of the
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`7 Cabilly II patent.
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`JURISDICTION AND VENUE
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`9.
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`This action arises under the Declaratory Judgment Act of 1934 (28 U.S.C. §§ 2201-
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`2201 ), Title 28 of the United States Code, for the purposes of detennining an actual and justiciable
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`controversy between the parties, and the patent laws of the United States, Title 35 of the United
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`States Code. This Court has subject matter jurisdiction pursuant to 28 U.S.C. §§ 1331 and 1338(a)
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`(2006).
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`10.
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`This Court has personal jurisdiction over Genentech based on its principal place of
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`business in California. This Court has personal jurisdiction over City of Hope based on its
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`organization under the laws of the State of California and because its principal place of operation is
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`in California.
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`11.
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`Venue is proper in this District pursuant to 28 U.S.C. § 1391 (2006) because both
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`19 Defendants reside in this District and a substantial part of the events or omissions giving rise to the
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`claims occurred in this District.
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`INTRADISTRJCT ASSIGNMENT
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`12.
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`A substantial part of the events or omissions giving rise to the claims occurred in the
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`San Francisco Division.
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`THE CAB ILLY PATENTS
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`13.
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`On April 8, 1983, Shmuel Cabilly, Herbert Heyneker, William Holmes, Arthur Riggs,
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`and Ronald Wetzel (the. "Cabilly Applicants") filed a patent application in the United States Patent
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`and Trademark Office ("PTO") that issued on March 28, 1989, as U.S. Patent 4,816,567 (the
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`"Cabilly I patent"). The Cabilly Applicants assigned their rights to Genentech and the City of Hope.
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`DM_US 23108491_1
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`3
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1180
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`Merck Ex. 1051, pg 1206
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`ca 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 4 of 17 Page ID #:4
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`Patent Interference
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`14.
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`At the time the Cabilly I patent issued, the Cabilly Applicants had a continuation
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`application (the "Cabilly II application") pending in the PTO. The Cabilly Applicants copied claims
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`from U.S. Patent 4,816,397 (the "Boss patent") in order to provoke the PTO Board of Patent Appeals
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`and Interferences to initiate an interference proceeding to determine whether the Boss patentees or
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`the Cabilly Applicants were entitled to priority for the inventions claimed in the Boss patent.
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`15.
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`In February 1991, the PTO Board declared a patent interference between the pending
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`8 Cabilly II application and the Boss patent on the ground that both the Boss patentees and the Cabilly
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`9 Applicants claimed the same purported invention. After seven years of adversarial proceedings in
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`the PTO, in August 1998, the PTO Board found that the Boss patentees were entitled to priority over
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`the Cabilly Applicants. See Cabilly v. Boss, 55 U.S.P.Q.2d 1238 (B.P.A.I. 1998). The PTO Board
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`concluded that the Cabilly Applicants had failed to establish conception or reduction to practice of
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`the claimed inventions prior to March 25, 1983 -the filing date of the Boss patent. According to the
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`PTO Board, "there is no evidence that immunoglobulins, multiple chain proteins, had been produced
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`by recombinant DNA techniques from a single host cell prior to March 25, 1983." Moreover, "the
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`evidence indicates that Cabilly et al. had but a hope or wish to produce active antibodies in
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`bacteria; and, there is no supporting evidence to establish the development of the means to
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`accomplish that result or evidence of a disclosure to a third party of complete conception."
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`(emphasis added). The Final Decision therefore indicated that the Cabilly Applicants were "not
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`entitled to a patent."
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`16.
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`In October 1998, Genentech filed an action in this District under 35 U.S.C. § 146
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`against the owner of the Boss patent, Celltech Therapeutics Ltd. ("Celltech"), to appeal the decision
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`23
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`of the PTO Board awarding priority to the Boss patent. Genentech, Inc. v. Cell tech Therapeutics
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`24 Ltd., Case No. C98-3926 (N.D. Cal.). In March 200 I, the parties to that action filed a notice of·
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`settlement and joint request for entry of settlement instruments. As part of their settlement
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`agreement, the parties asked the district court to find that, contrary to the PTO Board's prior
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`decision, Genentech's Cabilly Applicants were entitled to priority. On information and belief, as
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`part of the Genentech-Celltech agreement, Celltech obtained certain rights relating to the Cabilly II
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`DM_ US:231 08491_1
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`4
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1181
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`Merck Ex. 1051, pg 1207
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`

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`ca 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 5 of 17 Page ID #:5
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`.,.,
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`patent as well as certain payments from Genentech in exchange for its agreement to stipulate that the
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`2 Cabilly Applicants were entitled to priority for the inventions claimed in the Boss patent. The
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`precise tenns of the settlement agreement are confidential and, despite reasonable inquiry, unknown
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`to GSK.
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`17.
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`Notably, the Boss patent would have expired by 2006. By obtaining Celltech's
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`stipulation to priority of invention for the claimed subject matter of the Boss patent, GSK is
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`informed and believes that Genentech sought to extend the I ife of patent protection for the inventions
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`claimed in the Boss patent beyond the expiration date of the Boss patent.
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`18.
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`Pursuant to the Genentech-Celltech agreement, the district court issued an order
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`directing the PTO to vacate its detennination that the Boss applicants were entitled to priority, to
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`revoke the Boss patent, and to issue a patent to the Cabilly Applicants claiming the same subject
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`12 matter as the Boss patent. The Cabilly II patent issued on December 18, 200 I, and on its face is
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`assigned to Genentech, and, by certificate of correction, is also assigned to City of Hope.
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`19.
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`If the PTO Board's decision in favor of the Boss patent had not been reversed as a
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`result of the private Genentech-Celltech agreement, the Boss patent would have expired in 2006, and
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`the public would thereafter have been free to use the inventions claimed in the Cabilly II patent.
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`Instead, because Genentech and Celltech agreed to request that the court reverse that result,
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`18 Defendants received the Cabilly II patent, which will not expire until2018. Consequently, due to
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`the private Genentech-Celltech agreement, Defendants have ostensibly extended their power to
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`exclude others from making, using, or selling the inventions claimed in the Boss and Cabilly II
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`patent until 2018 -more than 35 years after their original 1983 patent application, and more than 12
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`years after the expiration of the Boss patent. The combined period of patent exclusivity secured by
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`23 Defendants for the Cabilly I and Cabilly II patents, which share the same patent specification, is 29
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`years.
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`20.
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`In 2008 alone, according to Genentech's 2009 Form 1 0-K filing, Defendants received
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`$298 million in royalties on the Cabilly II patent. In short, two years after the original expiration
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`date of the Boss patent, Genentech is receiving nearly $300 million in annual royalties on the
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`inventions claimed in the Boss patent.
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`DM US·2JI08491_1
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`5
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1182
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`Merck Ex. 1051, pg 1208
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`

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`Ca
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`2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 6 of 17 Page ID #:6
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`Patent Reexamination
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`21.
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`Two separate requests to re-examine the Cabilly II patent were submitted to the PTO
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`in 2005. The PTO originally concluded that the prior art submitted by the requestors raised
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`substantial new questions of patentability with respect to each of the claims ofthe Cabilly 11 patent
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`and commenced separate reexamination proceedings on July 7, 2005 and January 23, 2006. See
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`6 Decision Granting Ex Parte Reexamination, Reexamination Control No. 90/007,542 (July 7, 2005);
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`7 Decision Granting Ex Parte Reexamination, Reexamination Control No. 90/007,859 (January 23,
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`2006). The separate reexamination proceedings were merged on June 6, 2006.
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`22.
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`In an Advisory Action on July 19, 2008, the PTO maintained its final rejection ofthe
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`claims in the Cabilly II patent as invalid for reasons including obviousness-type double patenting.
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`II Ex Parte Reexamination Advisory Action, Reexamination Control Nos. 90/007,859 and 90/007,542
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`(July 19, 2008).
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`23.
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`In response to the final rejection, Defendants filed an Appeal Brief on December 9,
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`2008.
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`24.
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`After an Ex Parte Examiner Interview on February 13, 2009, Genentech amended
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`claims 21, 27, and 32 to overcome the obviousness-type double patenting rejection. See
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`17 Supplemental Amendment Under 37 C.F.R. § 1.550(b) (2007), Reexamination Control Nos.
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`90/007,859 and 90/007,542 (February 13, 2009).
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`25.
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`On February 23, 2009, the PTO issued a Notice of Intent to Issue a Reexamination
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`20 Certificate to Genentech confirming claims 1-20 and 33-36 and allowing amended claims 21, 27,
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`and 32. Notice of Intent to Issue Ex Parte Reexamination Certificate, Reexamination Control Nos.
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`90/007,859 and 90/007,542 (February 23, 2009). On May 19, 2009, the Ex Parte Reexamination
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`23 Certificate issued for U.S. Patent 6,331,415 C I with amended claims 21, 27, and 32. (Exhibit B).
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`24 Defendants' Admissions Regarding State of the Art in Apri/1983
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`26.
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`In order to overcome the PTO's obviousness-type double patenting rejections during
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`the reexamination, Defendants made a number of admissions in their December 2008 Appeal Brief
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`regarding the state of the art prior to the filing of the Cabilly II patent application in April 1983.
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`DM_US:23108491_1
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`6
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1183
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`Merck Ex. 1051, pg 1209
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`Ca 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 7 of 17 Page ID #:7
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`According to Defendants, the state of the art prior to the April 1983 filing of the Cabilly patent
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`application was as follows:
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`a.
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`"[I]n April 1983, the biological mechanisms that controlled expression of foreign
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`DNA and assembly of proteins were not well understood . This lack of understanding
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`was especially true for eukaryotic genes, which were known to be far more complex
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`than prokaryotic genes. As Dr. Harris, one of Owners' experts in this case, explained
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`in his 1983 review paper, 'it is clear that not all the rules governing the expression of
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`cloned genes have been elaborated and those rules that do exist are still largely
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`empirical.'" (Appeal Brief at 20)
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`b. "In early April of 1983, the field of generic engineering was still developing . . . . A
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`relatively small number of proteins had been made by recombinant DNA technology.
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`Almost all of those were relatively simple monomeric (i.e., one polypeptide chain)
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`proteins." (Appeal Brief Appendix at B551 [Harris Dec I.])
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`c. "As of April 1983, insulin was the only 'multimeric' protein that had been made
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`using genetic engineering." (Appeal Brief at 21)
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`d. " Several experts with actual experience in the field of the invention in April 1983
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`explained that those references cited by the Examiner that include experimental
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`results show a significant amount of unpredictability in achieving success in simpler
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`experiments than what is required by the '415 patent claims." (Appeal Brief at 28)
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`e. "[S]uccessful production of immunoglobulins was highly dependent on the sequence
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`· of expression and levels at which the two immunoglobulin genes were expressed."
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`(Appeal Brief at 63)
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`f.
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`"[L ]evels of expression of each immunoglobulin gene could affect production of the
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`other immunoglobulin polypeptide." (Appeal Brief at 63)
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`g. "Such a person would have been familiar with the many complications of producing
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`eukaryotic polypeptides in bacterial host cells known by April 1983." (Appeal Brief
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`at 73).
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`DM_US 23108491 _ 1
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`7
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1184
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`Merck Ex. 1051, pg 1210
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`

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`Ca 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 8 of 17 Page ID #:8
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`h. "I believe a person of ordinary skill in the art, in early April of 1983, would have
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`thought that successful expression of two immunoglobulin proteins in one
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`transformed host cell would have been unpredictable and that assembly of the two
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`proteins into an immunoglobulin tetramer would have been even more
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`unpredictable." (Appeal Brief Appendix at B224 [McKnight Dec!.])
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`1.
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`"Experimental results would have been important to a person of ordinary skill in the
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`art in April 1983 because many of the biological mechanisms that controlled
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`expression of foreign DNA and assembly of proteins were not well understood at that
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`time." (Appeal Brief Appendix at B376 [Second McKnight Decl.])
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`j . "Each of these papers shows that successful transformation and expression of even
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`one foreign immunoglobulin gene in a lymphoid host cell could not be reasonably
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`expected in April 1983. I do not believe these references can be read as suggesting
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`that something even more challenging- expressing two different foreign
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`immunoglobulin genes in one transformed cell -would have been something that
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`could be predictably achieved at that time." (Appeal Brief Appendix at B382
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`[Second McKnight Dec!.])
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`k. " .. . I disagree with the suggestion, that by early April 1983, my PNAS paper had
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`made routine or predictable the task of expressing exogenous immunoglobulin light
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`and heavy chain genes in the same cell. In later experiments, J attempted to use the
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`techniques described in the PNAS paper to introduce and express single Ig genes into
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`other lymphoid cell lines . Most of these experiments failed to produce stable
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`transfectants. Thus, my experience was that using the same transfection and selection
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`conditions described in the PNAS paper with other cell lines or other Ig genes did not
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`routinely yield stable transformants containing even a single exogenous Ig gene."
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`(Appeal Brief Appendix at B391 [Rice Decl.])
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`DM_US 23 108491 _1
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`8
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`COMPLAINT
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`Sanofi/Regeneron Ex. 1051, pg 1185
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`Merck Ex. 1051, pg 1211
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`

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`ca e 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 9 of 17 Page ID #:9
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`GSK'S OFATUMUMAB (ARZERRA™)
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`27.
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`Ofatumumab (Arzerra™) is a new, human monoclonal antibody which targets the
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`3 CD20 antigen, a naturally occurring protein present on B-lymphocytes, which is believed to be
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`involved in the mediation of lymphoproliferative and autoimmune diseases.
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`28.
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`Genmab A/S originally developed ofatumumab. In December 2006, GSK and
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`6 Genmab A/S entered into an agreement to co-develop ofatumumab for therapeutic use. Under the
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`terms of its agreements with Genmab, GSK has the exclusive right to make, use, import, offer to sell,
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`and sell ofatumumab (Arzerra™) in the United States.
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`29.
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`Pursuant to a contract with GSK, Lonza Biologics pic currently manufactures
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`10 Arzerra™ in the United Kingdom for commercial sale by GSK in the United States. In addition,
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`II
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`copies of the working cell bank used to produce Arzerra™ are maintained by Lonza Biologics, Inc.
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`in Portsmouth, New Hampshire. On information and belief, Lonza Biologics pic and Lonza
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`13 Biologics, Inc. (collectively "Lonza") may have received from Genentech certain rights or covenants
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`not to sue relating to the Cabilly II patent pursuant to the 2001 Settlement Agreement between
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`15 Cell tech and Genentech. The scope of those rights, however, is confidential and unknown to GSK,
`
`16
`
`despite reasonable efforts to ascertain what, if any, rights Lonza may have. Therefore, Genentech
`
`17
`
`has affirmed through its conduct and agreement with Lonza that permission is needed from
`
`18 Genentech for Lonza to manufacture recombinant antibody products.
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`19
`
`30.
`
`On October 26, 2009, GSK received accelerated approval from the U.S. Food and
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`20 Drug Administration ("FDA") to market Arzerra™ in the United States for the treatment of patients
`
`21 whose chronic lymphocytic leukemia ("CLL") is refractory to previous therapies (fludarabine and
`
`22
`
`alemtuzumab). Following that approval, GSK has begun marketing and selling Arzerra™ in the
`
`23 United States, doctors have begun prescribing Arzerra™, and patients suffering from refractory CLL
`
`24
`
`have begun taking Arzerra™ to treat their CLL.
`
`25
`
`26
`
`GSK'S DISPUTE WITH GENENTECH REGARDING CABILLY II PATENT
`
`31.
`
`Through its statements and actions, Genentech has made clear to the
`
`27
`
`biopharmaceutical industry generally and to GSK that it contends that the claims of the Cabilly II
`
`28
`
`patent effectively preclude others from commercially manufacturing recombinant monoclonal
`
`DM_ US·23108491_1
`
`9
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1186
`
`Merck Ex. 1051, pg 1212
`
`

`
`Cas 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 10 of 17 Page ID #:10
`~
`
`...,
`
`antibodies without Genentech's pennission. In 2002, after the Cabilly II patent issued, Sean
`
`2
`
`Johnston, then Genentech's Vice President of Intellectual Property and now Genentech's Senior
`
`3 Vice President and General Counsel said:
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`II
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`"The recently issued patent broadly covers the co-expression of immunoglobulin
`
`heavy and light chain genes in a single host cell ... We do not believe that the claims
`
`are limited by type of antibody (murine, humanized [90% human sequence], or
`
`human) or by host cell type."
`
`(''Genentech Awarded Critical Antibody Patent," Nature Biotechnology, vol. 20, p. I 08 (Feb.
`
`2002) (emphasis added).
`
`32.
`
`According to Defendants, the manufacturing methods claimed in the Cabilly II patent
`
`are "the backbone of recombinant antibody production in the biotech industry." (Centocor, Inc. v.
`
`12 Genentech, Inc., Case No. 2:08-cv-03573-MRP-CT (C.D. Cal.), 3/24/09 Opening Brief of Claim
`
`13 Construction).
`
`14
`
`33.
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`Genentech has asserted the Cabilly II patent in litigation against other manufacturers
`
`15 of recombinant monoclonal antibodies, including Medimmune, Inc. ("Medimmune") and Centocor
`
`16 Ortho Biotech Inc. ("Centocor"). On infonnation and belief, the recombinant methods used by GSK
`
`17
`
`18
`
`19
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`to produce Arzerra™ are similar to the recombinant methods used by Medimmune and Centocor to
`
`produce their monoclonal antibody products, Synagis®, ReoPro®, and Remicade®.
`
`34.
`
`On infonnation and belief, Genentech contends that the process and certain starting
`
`20 materials used to produce Arzerra ™ infringe one or more claims of the Cabilly II patent.
`
`21
`
`35.
`
`For example, both GSK's Arzerra™ and Medlmmune's Synagis® are produced by
`
`22
`
`genetically engineering mammalian host cells to produce the desired antibody in cell culture.
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`23 Arzerra™ is produced in a recombinant murine (mouse) cell line called NSO using standard
`
`24 mammalian cell cultivation and purification techniques. On information and belief, Synagis® is also
`
`25
`
`produced in a recombinant murine (mouse) cell line called NSO using standard mammalian cell
`
`26
`
`cultivation and purification techniques. Arzerra™ is an IgG I K monoclonal antibody comprised of
`
`27
`
`two heavy chains and two light chains. On infonnation and belief, Synagis® is also an IgG 1 K
`
`28 monoclonal antibody comprised of two heavy chains and two light chains. Like Arzerra™, on
`
`DM_US 23108491~1
`
`10
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1187
`
`Merck Ex. 1051, pg 1213
`
`

`
`Cas 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 11 of 17 Page ID #:11
`~·
`
`..,
`
`information and belief, Medlmmune's Synagis™ product is manufactured by Lonza. Since
`
`2 Genentech has previously enforced the Cabilly II patent against another Lonza customer that, on
`
`3
`
`4
`
`information and belief, uses the same NSO cell line as Lonza uses for GSK, the same or similar
`
`transformation process as Lonza uses for GSK, and the same or similar manufacturing process as
`
`5 Lonza uses for GSK, GSK is informed and believes that Genentech contends that the methods used
`
`6
`
`7
`
`8
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`to produce Arzerra™ infringe one or more claims of the Cabilly II patent.
`
`36.
`
`On information and belief, Genentech has also alleged that the corresponding
`
`recombinant methods and starting materials used to produce its Rituxan® antibody product fall
`
`9 within the scope of the Cabilly II patent. Like Arzerra™, Genentech's Rituxan® is produced by
`
`I 0
`
`genetically engineering mammalian host cells to produce the desired antibody in cell culture. Like
`
`11 Arzerra™, Genentech's Rituxan® is an JgG lK monoclonal antibody comprised of two heavy chains
`
`12
`
`and two light chains. Like Arzerra™, Genentech's Rituxan® is directed against the CD20 antigen.
`
`13 Like Arzerra™, Lonza has manufactured Rituxan® for Genentech. If Genentech contends that the
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`14 manufacturing process used by Lonza to produce Rituxan® for Genentech fell within the scope of
`
`15
`
`the Cabilly II patent, then GSK is informed and believes that Genentech also contends that the
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`16 manufacturing process used by Lonza to produce Arzerra™ for GSK also falls within the scope of
`
`I 7
`
`the Cabilly II patent.
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`18
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`19
`
`37.
`
`Since Defendants have consistently alleged that the use of well-known, conventional
`
`recombinant methods to produce monoclonal antibodies in mammalian cell culture is within the
`
`20
`
`scope of claims of the Cabilly II patent and have asserted the patent against others who are similarly
`
`21
`
`situated to GSK, Defendants' prior statements and conduct necessarily establish an actual and
`
`22
`
`substantial dispute between GSK and Defendants regarding the invalidity, unenforceability, and
`
`23
`
`non infringement of claims of the Cabilly II patent. Therefore, GSK has a reasonable apprehension
`
`24 of suit by Genentech regarding the Cabilly II patent.
`
`25
`
`38.
`
`In addition to the statements and conduct directed at others, Defendants, including
`
`26
`
`particularly Genentech, have made statements and engaged in conduct directed at GSK that create a
`
`real and immediate dispute between the parties regarding the Cabilly IJ patent.
`
`27
`
`28
`
`OM_ US 23108491_1
`
`11
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1188
`
`Merck Ex. 1051, pg 1214
`
`

`
`Cas 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 12 of 17 Page ID #:12
`'-'
`
`'-'
`
`39.
`
`Genentech has made public statements about pursuing an aggressive litigation policy
`
`2
`
`3
`
`to protect its products against competition and to protect against alleged infringement of the Cabilly
`
`II patent claims in its 2009 Form 1 0-K filing with the Securities and Exchange Commission.
`
`4 Genentech states:
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
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`12
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`"Intellectual property protection of our products is crucial to our business. Loss of
`
`effective intellectual property protection could result in lost sales to competing
`
`products and loss of royalty payments (for example, royalty income associated with
`
`the Cabilly patent) from licenses. We are often involved in disputes over contracts
`
`and intellectual property, and we work to resolve these disputes in confidential
`
`negotiations or litigation. We expect legal challenges in this area to continue. We
`
`plan to continue to build upon and defend our intellectual property position."
`
`(emphasis added)
`
`13 Genentech also states: "We have in the past been, are currently, and may in the future be involved
`
`14
`
`in material litigation and other legal proceedings related to our proprietary rights, such as the
`
`15 Cabilly patent litigation and reexamination . ... "(emphasis added)
`
`16
`
`40.
`
`In early 2009, Genentech made public statements specifically identifying Arzerra™
`
`17
`
`as an imminent competitor to Genentech's product Rituxan® in its filings with the Securities and
`
`18 Exchange Commission. In Genentech 's 2009 Form 1 0-K, Genentech states:
`
`19
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`20
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`21
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`22
`
`23
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`24
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`25
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`"Rituxan may face future competition in both hematology-oncology and RA from
`
`ArzerraTM (ofatumumab), an anti-CD20 antibody being co-developed by Genmab
`
`A/S and GSK. Genmab and GSK recently presented positive results from their
`
`pivotal trial for CLL at the American Society of Hematology meeting. They
`
`announced on January 30, 2009 that they filed for approval for Arzerra™ for
`
`monotherapy use in refractory CLL." (emphasis added)
`
`41.
`
`Taken together, Genentech's statements that it will enforce its intellectual property,
`
`26
`
`specifically the Cabilly II patent, to defend its products against competing products, and its
`
`27
`
`contention that GSK's Arzerra™ will be a competitor with Genentech's Rituxan® in hematology-
`
`28
`
`oncology, establish that a real and immediate dispute exists between parties with adverse legal
`
`DM_US:23108491_1
`
`12
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1189
`
`Merck Ex. 1051, pg 1215
`
`

`
`Cas 2:10-cv-02764-MRP-FMO Document 1 Filed 02/17/10 Page 13 of 17 Page 10 #:13
`.._;
`~
`
`interests concerning the Cabilly II patent. GSK therefore has a reasonable apprehension of suit by
`
`2 Genentech regarding the Cabilly II patent.
`
`42.
`
`Genentech and GSK also have had repeated discussions and interactions relating to
`
`the Cabilly II patent that further establish the existence of a substantial dispute.
`
`a.
`
`In 1991, one ofGSK's predecessors-in-interest, Wellcome Foundation Ltd., entered
`
`into a license agreement with Genentech that included certain license rights relating
`
`to what later issued as the Cabilly II patent with respect to antibodies targeting CD4.
`
`b.
`
`In 2002, Genentech and GSK entered into an agreement that provided for the parties
`
`to attempt to negotiate licenses under the Cabilly II patent for several different
`
`recombinant antibodies then in development by GSK. Licensing terms were
`
`ultimately never resolved and those antibody products have not yet been
`
`commercially sold in the United States.
`
`c.
`
`In 2005, there were renewed discussions between Genentech and GSK regarding
`
`licensing the Cabilly II patent for a monoclonal antibody called mepolizumab that
`
`targeted the antigen IL-5. The parties were unable to reach agreement because
`
`Genentech proposed onerous terms that GSK believed were commercially
`
`unreasonable for the product, which was ultimately withdrawn from the regulatory
`
`approval process.
`
`d.
`
`In 2005, a representative of Genentech, Tim Schwartz, asked GSK' s counsel, Frank
`
`Grassier, to begin a discussion regarding a "Cabilly license for BEXXAR (anti-
`
`CD20) now that GSK has acquired the rights to this product." Like Arzerra™,
`
`BEXXAR is an antibody that targets the antigen CD20.
`
`e. Mark Lemley, outside counsel for Genentech, and Sherry Knowles, Chief Patent
`
`Counsel for GSK are professional colleagues of mutual respect. In September 2008,
`
`following GSK's acquisition of rights to ArzerraTM, Mr. Lemley told Ms. Knowles
`
`that he believed the Cabilly II patent would issue following reexamination and asked
`
`what GSK would then do about the Cabilly II patent. On information and belief, Mr.
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`