Lloyd R. Day, Jr., State Bar No. 90875
`I)ayL@howrey.com
`
`Robert M. Galvin, State Bar No. I7] 508
`
`GalvinR@howrey.com
`Jackie N. Nakamura, State Bar No. 148531
`Nakamura.I@howrey.com
`HOWREY LLP
`I950 University Avenue, 4”’ Floor
`
`East Palo Alto, CA 94303
`Telephone: (650) 798-3500
`Facsimile:
`(650) 798-3600
`
`Q
`
`CLE£l,l(CHAHD _w
`I 9§NOFlTHERN'1l$g%ggTHIé:Ei%~GnT
`
`Attorneys for Plaintiffs
`GLAXO GROUP LIMITED and
`GLAXOSMITHKLINE LLC
`
`UNITED STATES DISTRICT COURT
`
`FOR THE NORTHERN DISTRICT OF CALIFORNIA
`
`GLAXO GROUP LIMITED and
`GLAXOSMITHKLINE LLC,
`
`Plaintiffs,
`
`vs.
`
`SAN F%‘;co1fi1oN
`
`Case No.:
`
`COMPLAINT FOR DECLARATORY
`JUDGMENT OF INVALIDITY,
`UNENFORCEABILITY, AND
`NONINFRING EMENT
`
`GENENTECH, INC., and CITY OF HOPE,
`
`Defendants.
`
`
`Plaintiffs Glaxo Group Limited and GlaxoSmithKline LLC (collectively, “GSK”), for their
`
`Complaint against Genentech, Inc. and City of Hope (collectively, “Defendants”), allege as follows:
`
`NATURE OF THE CASE
`
`1.
`
`GSK seeks a declaration that U.S. Patent 6,331,415 titled “Methods of Producing
`
`Immunoglobulins, Vectors and Transformed Host Cells for Use Therein” (the “Cabilly II patent”
`
`attached as Exhibit A), including the Ex Parte Reexamination Certificate issued pursuant to
`
`Reexamination Nos. 90/007,542 and 90/007,859 (attached as Exhibit B), is invalid, unenforceable,
`
`and not infringed by the manufacture, use, sale, offer to sell, or importation of GSK’s ofatumumab
`
`(Arzerram) antibody product.
`
`2.
`
`GSK recently began marketing and selling Arzerraw in the United States for the
`
`treatment of patients whose chronic lymphocytic leukemia (“CLL”) is refractory to previous
`
`DM_US:23l0849l_l
`
`l
`
`COMPLAINT
`
`ll
`
`I2
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`13
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`l5
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`l6
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`l7
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`18
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`19
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`20
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`21
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`22
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`24
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`25
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`26
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`28
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`Sanofi/Regeneron Ex. 1051, pg 1178
`
`Mylan Ex. 1051, pg 1178
`
`

`
`
`
`V
`
`VI
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`therapies (fludarabine and alemtuzumab). GSK brings this action to lift the cloud created by the
`
`imminent threat of Defendants’ enforcement of the Cabilly II patent against GSK. Without
`
`declaratory relief, the threat of enforcement of the Cabilly II patent poses a substantial risk of injury
`
`to GSK as well as the patients, nurses, and doctors now using Arzerram for treatment. The
`
`continued existence and enforcement of this invalid and unenforceable patent impedes not only the
`
`development and sale of ArzerraT”, but also the development and sale of other life-saving
`
`recombinant antibody products.
`
`3.
`
`Defendants have asserted that the Cabilly II patent broadly covers the use of certain
`
`well-known, conventional recombinant methods to produce any antibody product in any type of host
`
`cell. Defendants have filed infringement claims under the Cabilly ll patent against companies who
`
`have made and sold antibody products that were produced using recombinant methods similar to the
`
`recombinant methods used by GSK to make Arzerram. Defendant Genentech, Inc. has specifically
`
`identified GSK’s Arzerram antibody product as a potential competitor to one of Genentech’s own
`
`products, and has stated that it expects to be involved in future litigation relating to the enforcement
`
`of the Cabilly II patent. During GSK’s dealings with Genentech, Genentech has repeatedly taken the
`
`position that GSK requires a license under the Cabilly II patent to make and sell a variety of different
`
`antibody products, including products produced by the same or similar process as ArzerraTM. As
`
`recently as the Fall of 2008, after GSK acquired rights to Arzerram, counsel for Genentech inquired
`
`what GSK would do about the Cabilly II patent. Given Defendants’ past acts and statements and
`
`GSK’s sale of ArzerraTM in the United States, a real, immediate, and substantial dispute exists
`
`between the parties concerning the Cabilly II patent for which GSK now seeks declaratory relief.
`
`THE PARTIES
`
`4.
`
`Plaintiff Glaxo Group Limited d/b/a G1axoSmithKline is an English corporation
`
`having a principal place of business at Glaxo Wellcome House, Berkley Avenue, Greenford,
`
`Middlesex, UB6 ONN, United Kingdom.
`
`5.
`
`Plaintiff G1axoSmithKline LLC is a Delaware limited liability company having a
`
`principal place of business at One Franklin Plaza, Philadelphia, Pennsylvania, 19102.
`
`DMgUS:23l0849l_l
`
`COMPLAINT
`
`-I3
`
`‘\D00\lO\kn
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`10
`
`ll
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`12
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`l3
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`I4
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`15
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`16
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`l7
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`l8
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`19
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`20
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`2]
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`22
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`23
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`24
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`25
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`26
`
`27
`
`28
`
`Sanofi/Regeneron Ex. 1051, pg 1179
`
`Mylan Ex. 1051, pg 1179
`
`

`
`
`
`Va
`
`9
`
`6.
`
`Defendant Genentech, Inc. (“Genentech”) is a Delaware corporation having its
`
`principal place of business in South San Francisco, California.
`
`7.
`
`City of Hope is a California not-for-profit organization having its principal place of
`
`business in Duarte, California. On information and belief, City of Hope has a place of business in
`
`this District at 55 Hawthorne Street, Suite 450, San Francisco, California, 94105.
`8.
`On information and belief, Genentech and City of Hope are co-assignees of the
`
`Cabilly II patent.
`
`JURISDICTION AND VENUE
`
`9.
`
`This action arises under the Declaratory Judgment Act of I934 (28 U.S.C. §§ 2201-
`
`220l ), Title 28 of the United States Code, for the purposes of determining an actual andjusticiable
`
`controversy between the parties, and the patent laws of the United States, Title 35 of the United
`
`States Code. This Court has subject matterjurisdiction pursuant to 28 U.S.C. §§ 1331 and l338(a)
`
`(2006).
`
`10.
`
`This Court has personal jurisdiction over Genentech based on its principal place of
`
`business in California. This Court has personal jurisdiction over City of Hope based on its
`
`organization under the laws of the State of California and because its principal place of operation is
`
`in California.
`
`1].
`
`Venue is proper in this District pursuant to 28 U.S.C. § 1391 (2006) because both
`
`Defendants reside in this District and a substantial part of the events or omissions giving rise to the
`
`claims occurred in this District.
`
`INTRADISTRICT ASSIGNMENT
`
`12.
`
`A substantial part of the events or omissions giving rise to the claims occurred in the
`
`San Francisco Division.
`
`THE CABILLY PATENTS
`
`13.
`
`On April 8, 1983, Shmuel Cabilly, Herbert Heyneker, William Holmes, Arthur Riggs,
`
`and Ronald Wetzel (the, “Cabilly Applicants”) filed a patent application in the United States Patent
`
`and Trademark Office (“PTO”) that issued on March 28, I989, as U.S. Patent 4,816,567 (the
`
`“Cabilly I patent”). The Cabilly Applicants assigned their rights to Genentech and the City of Hope.
`
`3
`
`COMPLAINT
`
`DM_US:23l0849l_l
`
`Sanofi/Regeneron Ex. 1051, pg 1180
`
`Mylan Ex. 1051, pg 1180
`
`

`
`
`
`W
`
`‘U
`
`Patent Interference
`
`14.
`
`At the time the Cabilly I patent issued, the Cabilly Applicants had a continuation
`
`application (the “Cabilly [1 application”) pending in the PTO. The Cabilly Applicants copied claims
`
`from U.S. Patent 4,816,397 (the “Boss patent”) in order to provoke the PTO Board of Patent Appeals
`
`and Interferences to initiate an interference proceeding to determine whether the Boss patentees or
`
`the Cabilly Applicants were entitled to priority for the inventions claimed in the Boss patent.
`
`15.
`
`In February 1991, the PTO Board declared a patent interference between the pending
`
`Cabilly II application and the Boss patent on the ground that both the Boss patentees and the Cabilly
`
`Applicants claimed the same purported invention. After seven years of adversarial proceedings in
`
`the PTO, in August 1998, the PTO Board found that the Boss patentees were entitled to priority over
`
`the Cabilly Applicants. See Cabilly v. Boss, 55 U.S.P.Q.2d 1238 (B.P.A.I. 1998). The PTO Board
`
`concluded that the Cabilly Applicants had failed to establish conception or reduction to practice of
`
`the claimed inventions prior to March 25, 1983 — the filing date of the Boss patent. According to the
`
`PTO Board, “there is no evidence that immunoglobulins, multiple chain proteins, had been produced
`
`by recombinant DNA techniques from a single host cell prior to March 25, 1983.” Moreover, “the
`
`evidence indicates that Cabilly et al. had but a hope or wish to produce active antibodies in
`
`bacteria; and, there is no supporting evidence to establish the development of the means to
`
`accomplish that result or evidence of a disclosure to a third party of complete conception."
`
`(emphasis added). The Final Decision therefore indicated that the Cabilly Applicants were “not
`
`entitled to a patent.”
`
`16.
`
`In October 1998, Genentech filed an action in this District under 35 U.S.C. § 146
`
`against the owner of the Boss patent, Celltech Therapeutics Ltd. (“Celltech”), to appeal the decision
`
`of the PTO Board awarding priority to the Boss patent. Genentech, Inc. v. Celltech Therapeutics
`
`Ltd, Case No. C98-3926 (N.D. Cal.).
`
`In March 2001, the parties to that action filed a notice of‘
`
`settlement and joint request for entry of settlement instruments. As part of their settlement
`
`agreement, the parties asked the district court to find that, contrary to the PTO Board’s prior
`
`decision, Genentech’s Cabilly Applicants were entitled to priority. On information and belief, as
`
`part of the Genentech—Celltech agreement, Celltech obtained certain rights relating to the Cabilly II
`
`4
`
`COMPLAINT
`
`DM_US:23l0849l_l
`
`Sanofi/Regeneron Ex. 1051, pg 1181
`
`Mylan Ex. 1051, pg 1181
`
`

`
`
`
`‘U
`
`9
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`patent as well as certain payments from Genentech in exchange for its agreement to stipulate that the
`
`Cabilly Applicants were entitled to priority for the inventions claimed in the Boss patent. The
`
`precise temis of the settlement agreement are confidential and, despite reasonable inquiry, unknown
`
`to GSK.
`
`17.
`
`Notably, the Boss patent would have expired by 2006. By obtaining Celltech’s
`
`stipulation to priority of invention for the claimed subject matter of the Boss patent, GSK is
`
`informed and believes that Genentech sought to extend the life of patent protection for the inventions
`
`claimed in the Boss patent beyond the expiration date of the Boss patent.
`
`l8.
`
`Pursuant to the Genentech-Celltech agreement, the district court issued an order
`
`directing the PTO to vacate its determination that the Boss applicants were entitled to priority, to
`
`revoke the Boss patent, and to issue a patent to the Cabilly Applicants claiming the same subject
`
`matter as the Boss patent. The Cabilly II patent issued on December 18, 2001, and on its face is
`
`assigned to Genentech, and, by certificate of correction, is also assigned to City of Hope.
`
`19.
`
`If the PTO Board’s decision in favor of the Boss patent had not been reversed as a
`
`result of the private Genentech-Celltech agreement, the Boss patent would have expired in 2006, and
`
`the public would thereafter have been free to use the inventions claimed in the Cabilly II patent.
`
`Instead, because Genentech and Celltech agreed to request that the court reverse that result,
`
`Defendants received the Cabilly II patent, which will not expire until 2018. Consequently, due to
`
`the private Genentech-Celltech agreement, Defendants have ostensibly extended their power to
`exclude others from making, using, or selling the inventions claimed in the Boss and Cabilly II
`
`patent until 2018 — more than 35 years after their original 1983 patent application, and more than 12
`
`years after the expiration of the Boss patent. The combined period of patent exclusivity secured by
`
`Defendants for the Cabilly I and Cabilly II patents, which share the same patent specification, is 29
`
`years.
`
`20.
`
`In 2008 alone, according to Genentech’s 2009 Form l0-K filing, Defendants received
`
`$298 million in royalties on the Cabilly II patent.
`
`In short, two years after the original expiration
`
`date ofthe Boss patent, Genentech is receiving nearly $300 million in annual royalties on the
`
`inventions claimed in the Boss patent.
`
`DM ,us~23|o349i_1
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1182
`
`Mylan Ex. 1051, pg 1182
`
`

`
`Patent Reexamination
`
`21.
`
`Two separate requests to re-examine the Cabilly II patent were submitted to the PTO
`
`in 2005. The PTO originally concluded that the prior art submitted by the requestors raised
`
`substantial new questions of patentability with respect to each ofthe claims ofthe Cabilly II patent
`
`and commenced separate reexamination proceedings on July 7, 2005 and January 23, 2006. See
`
`Decision Granting Ex Parte Reexamination, Reexamination Control No. 90/007,542 (July 7, 2005);
`
`Decision Granting Ex Parte Reexamination, Reexamination Control No. 90/007,859 (January 23,
`
`2006). The separate reexamination proceedings were merged on June 6, 2006.
`
`22.
`
`In an Advisory Action on July 19, 2008, the PTO maintained its final rejection ofthe
`
`claims in the Cabilly II patent as invalid for reasons including obviousness-type double patenting.
`
`Ex Parte Reexamination Advisory Action, Reexamination Control Nos. 90/007,859 and 90/007,542
`
`(July 19, 2008).
`
`23.
`
`In response to the final rejection, Defendants filed an Appeal Brief on December 9,
`
`2008.
`
`24.
`
`After an Ex Parte Examiner Interview on February 13, 2009, Genentech amended
`
`claims 21, 27, and 32 to overcome the obviousness-type double patenting rejection. See
`
`Supplemental Amendment Under 37 C.F.R. § 1.550(b) (2007), Reexamination Control Nos.
`
`90/007,859 and 90/007,542 (February 13, 2009).
`
`25.
`
`On February 23, 2009, the PTO issued a Notice of Intent to Issue a Reexamination
`
`Certificate to Genentech confirming claims 1-20 and 33-36 and allowing amended claims 21, 27,
`
`and 32. Notice of Intent to Issue Ex Parte Reexamination Certificate, Reexamination Control Nos.
`
`90/007,859 and 90/007,542 (February 23, 2009). On May 19, 2009, the Ex Parte Reexamination
`
`Certificate issued for U.S. Patent 6,331,415 C1 with amended claims 21, 27, and 32. (Exhibit B).
`
`Defendants ’ Admissions Regarding State of the Art in April 1983
`
`26.
`
`In order to overcome the PTO’s obviousness-type double patenting rejections during
`
`the reexamination, Defendants made a number of admissions in their December 2008 Appeal Brief
`
`regarding the state ofthe art prior to the filing ofthe Cabilly II patent application in April 1983.
`
`10
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`23
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`24
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`25
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`26
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`27
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`28
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`DM-US:23l0849l_l
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1183
`
`Mylan Ex. 1051, pg 1183
`
`

`
` H
`
`According to Defendants, the state of the art prior to the April 1983 filing of the Cabilly patent
`
`application was as follows:
`
`a.
`
`“[I]n April 1983, the biological mechanisms that controlled expression of foreign
`
`DNA and assembly of proteins were not well understood. This lack of understanding
`
`was especially true for eukaryotic genes, which were known to be far more complex
`
`than prokaryotic genes. As Dr. Harris, one of Owners’ experts in this case, explained
`
`in his 1983 review paper, ‘it is clear that not all the rules governing the expression of
`
`cloned genes have been elaborated and those rules that do exist are still largely
`
`empirical.”’ (Appeal Brief at 20)
`
`b. “In early April of 1983, the field of generic engineering was still developing .
`
`.
`
`.
`
`. A
`
`relatively small number of proteins had been made by recombinant DNA technology.
`
`Almost all of those were relatively simple monomeric (i.e., one polypeptide chain)
`
`proteins.” (Appeal Brief Appendix at B551 [Harris Decl.])
`
`c.
`
`“As of April 1983, insulin was the only ‘multimeric’ protein that had been made
`
`using genetic engineering.” (Appeal Brief at 21)
`
`d. “Several experts with actual experience in the field ofthe invention in April 1983
`
`explained that those references cited by the Examiner that include experimental
`
`results show a significant amount of unpredictability in achieving success in simpler
`
`experiments than what is required by the ‘4l5 patent claims.” (Appeal Brief at 28)
`
`e.
`
`“[S]uccessful production of immunoglobulins was highly dependent on the sequence
`
`of expression and levels at which the two immunoglobulin genes were expressed.”
`
`(Appeal Brief at 63)
`
`f.
`
`“[L]evels of expression of each immunoglobulin gene could affect production ofthe
`
`other immunoglobulin polypeptide.” (Appeal Brief at 63)
`
`g. “Such a person would have been familiar with the many complications of producing
`
`eukaryotic polypeptides in bacterial host cells known by April l983.” (Appeal Brief
`
`at 73).
`
`DM_US:23lO849l_l
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1184
`
`Mylan Ex. 1051, pg 1184
`
`

`
` V
`
`U
`
`h.
`
`“I believe a person of ordinary skill in the art, in early April of 1983, would have
`
`thought that successful expression of two immunoglobulin proteins in one
`
`transformed host cell would have been unpredictable and that assembly of the two
`
`proteins into an immunoglobulin tetramer would have been even more
`
`unpredictable.” (Appeal Brief Appendix at B224 [McKnight Decl.])
`
`“Experimental results would have been important to a person of ordinary skill in the
`
`art in April 1983 because many ofthe biological mechanisms that controlled
`
`expression of foreign DNA and assembly of proteins were not well understood at that
`
`time.” (Appeal Brief Appendix at B376 [Second McKnight Decl.])
`
`“Each of these papers shows that successful transformation and expression of even
`
`one foreign immunoglobulin gene in a lymphoid host cell could not be reasonably
`
`expected in April 1983.
`
`I do not believe these references can be read as suggesting
`
`that something even more challenging — expressing t_wg different foreign
`
`immunoglobulin genes in one transformed cell — would have been something that
`
`could be predictably achieved at that time.” (Appeal Brief Appendix at B382
`
`[Second McKnight Decl.])
`
`“. .
`
`.
`
`I disagree with the suggestion, that by early April 1983, my PNAS paper had
`
`made routine or predictable the task of expressing exogenous immunoglobulin light
`
`and heavy chain genes in the same cell.
`
`In later experiments, I attempted to use the
`
`techniques described in the PNAS paper to introduce and express single lg genes into
`
`other lymphoid cell lines. Most ofthese experiments failed to produce stable
`
`transfectants. Thus, my experience was that using the same transfection and selection
`
`conditions described in the PNAS paper with other cell lines or other lg genes did not
`
`routinely yield stable transforrnants containing even a single exogenous lg gene.”
`
`(Appeal Brief Appendix at B391 [Rice Decl.])
`
`DM_US:23 l0849l_l
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1185
`
`Mylan Ex. 1051, pg 1185
`
`

`
`
`
`GSK’S OFATUMUMAB (ARZERRA““)
`
`27.
`
`Ofatumumab (Arzerram) is a new, human monoclonal antibody which targets the
`
`CD20 antigen, a naturally occurring protein present on B-lymphocytes, which is believed to be
`
`involved in the mediation of lymphoproliferative and autoimmune diseases.
`
`28.
`
`Genmab A/S originally developed ofatumumab.
`
`In December 2006, GSK and
`
`Genmab A/S entered into an agreement to co-develop ofatumumab for therapeutic use. Under the
`
`terms ofits agreements with Genmab, GSK has the exclusive right to make, use, import, offer to sell,
`
`and sell ofatumumab (Arzerram) in the United States.
`
`29.
`
`Pursuant to a contract with GSK, Lonza Biologics plc currently manufactures
`
`Arzerram in the United Kingdom for commercial sale by GSK in the United States.
`
`In addition,
`
`copies of the working cell bank used to produce ArzerraTM are maintained by Lonza Biologics, Inc.
`
`in Portsmouth, New Hampshire. On information and belief, Lonza Biologics plc and Lonza
`
`Biologics, Inc. (collectively “Lonza”) may have received from Genentech certain rights or covenants
`
`not to sue relating to the Cabilly II patent pursuant to the 200l Settlement Agreement between
`
`Celltech and Genentech. The scope of those rights, however, is confidential and unknown to GSK,
`
`despite reasonable efforts to ascertain what, if any, rights Lonza may have. Therefore, Genentech
`
`has affirmed through its conduct and agreement with Lonza that permission is needed from
`
`Genentech for Lonza to manufacture recombinant antibody products.
`
`30.
`
`On October 26, 2009, GSK received accelerated approval from the U.S. Food and
`
`Drug Administration (“FDA”) to market Arzerram in the United States for the treatment of patients
`
`whose chronic lymphocytic leukemia (“CLL”) is refractory to previous therapies (fludarabine and
`
`alemtuzumab). Following that approval, GSK has begun marketing and selling ArzerraTM in the
`
`United States, doctors have begun prescribing ArzerraT"", and patients suffering from refractory CLL
`have begun taking ArzerraT"" to treat their CLL.
`I
`
`GSK’S DISPUTE WITH GENENTECH REGARDING CABILLY II PATENT
`
`31.
`
`Through its statements and actions, Genentech has made clear to the
`
`biopharmaceutical industry generally and to GSK that it contends that the claims of the Cabilly II
`
`patent effectively preclude others from commercially manufacturing recombinant monoclonal
`
`9
`
`COMPLAINT
`
`DM_US'23l0849l_l
`
`Sanofi/Regeneron Ex. 1051, pg 1186
`
`Mylan Ex. 1051, pg 1186
`
`

`
` 9
`
`antibodies without Genentech’s permission.
`
`In 2002, after the Cabilly II patent issued, Sean
`
`Johnston, then Genentech’s Vice President of Intellectual Property and now Genentech’s Senior
`
`Vice President and General Counsel said:
`
`“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. I08 (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.
`
`Genentech, Inc., Case No. 2:08-cv-03573-MRP-CT (C.D. Cal.), 3/24/09 Opening Brief of Claim
`
`Construction).
`
`‘
`
`33.
`
`Genentech has asserted the Cabilly II patent in litigation against other manufacturers
`
`of recombinant monoclonal antibodies, including Medlmmune, Inc. (“MedImmune”) and Centocor
`
`Ortho Biotech Inc. (“Centocor”). On information and belief, the recombinant methods used by GSK
`
`to produce Arzerram are similar to the recombinant methods used by Medlmmune and Centocor to
`
`produce their monoclonal antibody products, Synagis®, ReoPro®, and Remicade®.
`
`34.
`
`On information and belief, Genentech contends that the process and certain starting
`
`
`
`aterials used to produce Arzerram infringe one or more claims of the Cabilly II patent.
`
`35.
`
`For example, both GSK’s Arzerram and MedImmune’s Synagis® are produced by
`
`enetically engineering mammalian host cells to produce the desired antibody in cell culture.
`
`Arzerram is produced in a recombinant murine (mouse) cell line called NSO using standard
`
`mammalian cell cultivation and purification techniques. On information and belief, Synagis® is also
`
`produced in a recombinant murine (mouse) cell line called NSO using standard mammalian cell
`
`cultivation and purification techniques. Arzerram is an IgGli< monoclonal antibody comprised of
`
`two heavy chains and two light chains. On information and belief, Synagis® is also an IgGl K
`
`monoclonal antibody comprised of two heavy chains and two light chains. Like Arzerram, on
`
`10
`
`COMPLAINT
`
`DM_US:23l08491_l
`
`Sanofi/Regeneron Ex. 1051, pg 1187
`
`Mylan Ex. 1051, pg 1187
`
`

`
`
`if
`‘V
`
`information and belief, MedImmune’s SynagisTM product is manufactured by Lonza. Since
`
`Genentech has previously enforced the Cabilly II patent against another Lonza customer that, on
`
`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
`
`Lonza uses for GS K, GSK is informed and believes that Genentech contends that the methods used
`
`to produce Arzerram 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
`
`within the scope of the Cabilly II patent. Like Arzerram, Genentech’s Rituxan® is produced by
`
`genetically engineering mammalian host cells to produce the desired antibody in cell culture. Like
`
`Arzerram, Genentech’s Rituxan® is an lgG l1< monoclonal antibody comprised of two heavy chains
`
`and two light chains. Like Arzerram, Genentech’s Rituxan® is directed against the CD20 antigen.
`
`Like Arzerram, Lonza has manufactured Rituxan® for Genentech. If Genentech contends that the
`
`manufacturing process used by Lonza to produce Rituxan® for Genentech fell within the scope of
`
`the Cabilly II patent, then GSK is informed and believes that Genentech also contends that the
`
`manufacturing process used by Lonza to produce Arzerram for GSK also falls within the scope of
`
`the Cabilly II patent.
`
`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
`
`scope of claims of the Cabilly ll patent and have asserted the patent against others who are similarly
`
`situated to GSK, Defendants’ prior statements and conduct necessarily establish an actual and
`
`substantial dispute between GSK and Defendants regarding the invalidity, unenforceability, and
`
`noninfringement of claims of the Cabilly II patent. Therefore, GSK has a reasonable apprehension
`
`of suit by Genentech regarding the Cabilly II patent.
`
`38.
`
`In addition to the statements and conduct directed at others, Defendants, including
`
`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 II patent,
`
`DM_US:23 l0849l_l
`
`ll
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1188
`
`Mylan Ex. 1051, pg 1188
`
`

`
`
`if
`V
`
`39.
`
`Genentech has made public statements about pursuing an aggressive litigation policy
`
`to protect its products against competition and to protect against alleged infringement of the Cabilly
`
`II patent claims in its 2009 Form l0-K filing with the Securities and Exchange Commission.
`
`Genentech states:
`
`“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)
`
`Genentech also states: “We have in the past been, are currently, and may in the future be involved
`
`in material litigation and other legal proceedings related to our proprietary rights, such as the
`
`Cabilly patent litigation and reexamination .
`
`.
`
`. .” (emphasis added)
`
`40.
`
`In early 2009, Genentech made public statements specifically identifying Arzerram
`
`as an imminent competitor to Genentech’s product Rituxan® in its filings with the Securities and
`
`Exchange Commission.
`
`In Genentech’s 2009 Form 10-K, Genentech states:
`
`“Rituxan may face future competition in both hematology-oncology and RA from
`
`ArzerraT’" (ofatumumab), an anti-CD20 antibody being co-developed by Genmab
`
`NS 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 ArzerraTM for
`
`monotherapy use in refractory CLL.” (emphasis added)
`
`41.
`
`Taken together, Genentech’s statements that it will enforce its intellectual property,
`
`specifical ly the Cabilly II patent, to defend its products against competing products, and its
`
`contention that GSK’s Arzerram will be a competitor with Genentech’s Rituxan® in hematology-
`
`oncology, establish that a real and immediate dispute exists between parties with adverse legal
`
`1 2
`
`COMPLAINT
`
`DM_US:23l0849l_1
`
`Sanofi/Regeneron Ex. 1051, pg 1189
`
`Mylan Ex. 1051, pg 1189
`
`

`
`
`
`VJ
`
`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 of GSK’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 ll patent with respect to antibodies targeting CD4.
`
`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.
`
`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.
`
`In 2005, a representative of Genentech, Tim Schwartz, asked GSK’s counsel, Frank
`
`Grassler, to begin a discussion regarding a “Cabilly license for BEXXAR (anti-
`
`CD20) now that GSK has acquired the rights to this product.” Like ArzerraTM,
`
`BEXXAR is an antibody that targets the antigen CD20.
`
`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 ofrights to Arzerram, 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.
`
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`28
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`DM_US:23 l0849l_l
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`13
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`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1190
`
`Mylan Ex. 1051, pg 1190
`
`

`
` U
`
`5-:
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`28
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`Lemley believed the Cabilly ll patent would be of interest to GSK, and his remarks
`
`conveyed that impression to Ms. Knowles.
`
`43.
`
`Given Genentech’s past positions and statements regarding the scope of the Cabilly ll
`
`patent and the fact that GSK has begun marketing and selling Arzerram in the United States without
`
`a direct license from Genentech, the dispute between the parties is real and immediate.
`
`44.
`
`The threat of litigation by Genentech to assert the Cabilly II patent against ArzerraTM
`
`is underscored by the parties’ past legal disputes. Throughout the 1990s and early 2000s, Genentech
`
`and GSK’s predecessors-in-interest were embroiled in multiple patent infringement actions,
`
`including at least one relating to recombinant antibody production.
`
`Prior Action in the Southern District of Florida
`
`45.
`
`To protect itself from the disruption of its commercial launch of Arzerram and secure
`
`a timely adjudication of its dispute with Genentech regarding the Cabilly II patent, on October 8,
`
`2009, GSK filed a claim for declaratory judgment in the Southern District of Florida against
`
`Defendants. See Glaxo Group Ltd. v. Genentech, Inc., Case No. 09-61608-CIV-
`
`LENARD/TURNOFF (S.D. Fla.). Defendants moved to dismiss the Florida complaint for lack of
`
`subj ect matter jurisdiction or, in the alternative, to transfer the action from the Southern District of
`
`Florida to the Central District of California.
`
`In their motion to dismiss, Defendants characterized
`
`GSK’s action as “premature” because, among other things,
`
`a.
`
`“At the time that plaintiffs (collectively ‘GSK’) filed this complaint, GSK had not
`
`received FDA approval for or made any commercial sales of ArzerraTM .
`
`.
`
`.
`
`b. “GSK had no communications at all with Genentech or City of Hope regarding the
`
`Cabilly ll patent in connection with Arzerram.”
`
`Notably, Defendants did not state that they would not assert the Cabilly Il patent against GSK’s
`
`ArzerraTM product.
`
`46.
`
`In their motion to transfer venue, Defendants challenged venue in Florida because,
`
`among other things, none of the parties were based in Florida. According to Defendants, “the locus
`
`of operative facts was in California” and “Califomia is more convenient and less expensive for the
`
`parties and witnesses.”
`
`DM_US:23l0849l_l
`
`14
`
`COMPLAINT
`
`Sanofi/Regeneron Ex. 1051, pg 1191
`
`Mylan Ex. 1051, pg 1191
`
`

`
`
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