Case 1:14-cv-01453-LPS Document 60 Filed 12/23/15 Page 1 of 5 PageID #: 1798
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`MEDA PHARMACEUTICALS INC. and
`CIPLA LTD.,
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`C.A. No. 14-1453-LPS
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`Plaintiffs,
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`v.
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`APOTEX INC. and APOTEX CORP.,
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`Defendants.
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`PLAINTIFFS MEDA AND CIPLA’S RESPONSE TO
`DEFENDANTS’ CLAIM CONSTRUCTION TUTORIAL
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`Steven J. Balick (#2114)
`John G. Day (#2403)
`Andrew C. Mayo (#5207)
`ASHBY & GEDDES
`500 Delaware Ave., 8th Floor
`P.O. Box 1150
`Wilmington, DE 19899
`(302) 654-1888
`sbalick@ashby-geddes.com
`jday@ashby-geddes.com
`amayo@ashby-geddes.com
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`Attorneys for Plaintiffs
`Meda Pharmaceuticals Inc. and Cipla Ltd.
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`Of Counsel:
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`H. Keeto Sabharwal
`Dennies Varughese
`Uma N. Everett
`Rami Bardenstein
`Dallin G. Glenn
`Joshua I. Miller
`Josephine J. Kim
`STERNE, KESSLER, GOLDSTEIN &
` FOX P.L.L.C.
`1100 New York Ave., N.W., Suite 800
`Washington, DC 20005-3934
`(202) 371-2600
`
`Dated: December 23, 2015
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`Case 1:14-cv-01453-LPS Document 60 Filed 12/23/15 Page 2 of 5 PageID #: 1799
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`I.
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`Introduction
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`Plaintiffs Meda Pharmaceuticals Inc. and Cipla Ltd. (together, “Plaintiffs”) submit this
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`Response to the Claim Construction Tutorial of Defendants Apotex Inc. and Apotex Corp.
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`(together, “Apotex”) to address certain inaccuracies and improper arguments related to invalidity
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`and claim construction in Apotex’s tutorial.
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`II. Apotex’s Tutorial Provides a Selective Recitation of the Technology to Advance
`Improper Invalidity Arguments
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`Apotex provides a selective view of the history of the active ingredients of the claimed
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`product, as well as their mechanism of action1 to advance its invalidity positions before expert
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`discovery. Plaintiffs will briefly clarify Apotex’s misleading statements here and will provide
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`more detail during expert discovery and at trial. For example, Apotex’s “History of Drug
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`Substances at Issue” provides only a selective list of the alleged dates of discovery of the class of
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`antihistamines and corticosteroids and the use, publication, and sale of two particular types. This
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`leaves the false impression that the active ingredients in the claimed formulation have been
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`known and used for decades. (Apotex Tutorial at 9-16.)
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`As an initial matter, the summary conflates the many different types of corticosteroids
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`and antihistamines that have undergone substantial evolution over time, such as the reduction in
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`sedative side effects achieved by new chemical structures of second-generation antihistamines
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`compared to first-generation antihistamines. The summary also ignores the development of
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`various dosage forms of antihistamines and corticosteroids (e.g. oral, nasal). Finally, the
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`1 On slide 18, Apotex identifies histamine as being “shown in purple” but Plaintiffs
`assume this is an inadvertent error as the mast cell is shown in purple and histamine is shown in
`green-blue.
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`Case 1:14-cv-01453-LPS Document 60 Filed 12/23/15 Page 3 of 5 PageID #: 1800
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`summary fails to distinguish the conditions treated by the various dosage forms or the knowledge
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`and understanding required to treat these different conditions.
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`Apotex also oversimplifies the operation of fluticasone, a corticosteroid, in its slide titled
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`“Fluticasone Mechanism of Action.” (Id. at 21.) While Apotex correctly states that fluticasone
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`works by reducing inflammation, Apotex incorrectly attributes this effect to “reducing the
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`activity” of three cell types: mast cells, eosinophils, and basophils, “thus reducing the amount of
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`histamine or other related substances released.” Apotex confuses the science in order to advance
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`improper invalidity arguments that “the mechanism of action for corticosteroids complements
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`the mechanism of action of antihistamines” and that “the patents at issue involve the combination
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`of two well-known drug substances.” (Id. at 22.)
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`The literature published by the priority date and even after, however, demonstrates that
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`the mechanism of action of fluticasone propionate is more complicated and less well understood
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`than Apotex suggests. While mast cells, eosinophils, and basophils, among others cells and
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`molecules, are involved in the inflammatory response, the exact mechanism of action of
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`fluticasone and other corticosteroids is unknown. For example, a 2001 publication observes that
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`although the exact mechanism of action of intranasal steroids are not known, the major pathway
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`involves binding of the steroid molecule to a cytoplasmic receptor that is then transported to the
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`nucleus where it binds to the DNA at the glucocorticoid response element. This results in
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`inhibition of a variety of pro-inflammatory cytokines that decrease the inflammatory response.
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`See, e.g., Joint Claim Construction Ex. 39, Galant and Wilkinson, Clinical Prescribing of
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`Allergic Rhinitis Medication in the Preschool and Young School-Age Child, BioDrugs Vol. 15,
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`No. 7, 453-463 (2001). Further, the label for Flonase®, GlaxoSmithKline’s fluticasone
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`propionate nasal spray which received FDA approval in 1994, states that “[t]he precise
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`Case 1:14-cv-01453-LPS Document 60 Filed 12/23/15 Page 4 of 5 PageID #: 1801
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`mechanism through which fluticasone propionate affects allergic rhinitis symptoms is not
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`known.” Product Information for Flonase® (fluticasone propionate) Nasal Spray, 50 mcg, at
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`Apotex’s Opening Claim Construction Brief at Ex. G, APOTEX_AZFL 0060187.
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`Finally, on the last slide of Apotex’s tutorial, it appears that Apotex is arguing its validity
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`case when it states that “nasal sprays containing both antihistamines and corticosteroids were
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`also specifically known in the prior art to the asserted patents” citing “EP 0780127 A1 (1997).”
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`(Apotex Tutorial at 22.) Apotex’s statement is wholly unrelated to the background of the
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`technology at issue, and it also omits that the USPTO Examiner thoroughly considered the cited
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`reference and similar arguments during prosecution of the asserted U.S. Patent No. 8,168,620
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`(“the ’620 patent”). The patentee overcame these arguments and the reference, and the USPTO
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`found the claims to be patentable and issued both asserted patents.[1] During expert discovery,
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`Plaintiffs will provide a more thorough overview of the state of the art, but until that time,
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`Apotex’s presentation of its invalidity arguments is inappropriate.
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`III. Apotex’s Tutorial Advances Claim Construction Arguments
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`Throughout the tutorial, Apotex bases its presentation on its proposed construction of the
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`terms “administration” and “condition,” which results in a tutorial that reflects Apotex’s
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`litigation position, rather than the facts of a technology tutorial. For example, in the “Nature of
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`this Action” slide Apotex recites an argument raised repeatedly in the “administration” section of
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`its claim construction brief, that “[a]s discussed in the patents, the active ingredients azelastine
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`and fluticasone ‘can be administered simultaneously, … separately or sequentially.’” (Apotex
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`[1] In addition, Apotex fails to mention that the European Patent Office (EPO) also
`considered this reference during a post-grant review initiated by a third party against a European
`counterpart to the ’620 patent. The EPO also found the claims patentable over this reference. See
`In re EP 1519 731 B1 (Eur. Pat. Off., Jan. 19, 2012).
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`Case 1:14-cv-01453-LPS Document 60 Filed 12/23/15 Page 5 of 5 PageID #: 1802
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`Tutorial at 3.) Likewise Apotex repeatedly pushes its construction of “condition” without
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`providing any background on how the technology works or noting the conditions set forth in the
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`ASHBY & GEDDES
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`/s/ Andrew C. Mayo
`_________________________________
`Steven J. Balick (#2114)
`John G. Day (#2403)
`Andrew C. Mayo (#5207)
`500 Delaware Ave., 8th Floor
`P.O. Box 1150
`Wilmington, DE 19899
`(302) 654-1888
`sbalick@ashby-geddes.com
`jday@ashby-geddes.com
`amayo@ashby-geddes.com
`
`Attorneys for Plaintiffs
`Meda Pharmaceuticals Inc. and Cipla Ltd.
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`patent and file history.
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`Of Counsel:
`
`H. Keeto Sabharwal
`Dennies Varughese
`Uma N. Everett
`Rami Bardenstein
`Dallin G. Glenn
`Joshua I. Miller
`Josephine J. Kim
`STERNE, KESSLER, GOLDSTEIN &
` FOX P.L.L.C.
`1100 New York Ave., N.W., Suite 800
`Washington, DC 20005-3934
`(202) 371-2600
`
`Dated: December 23, 2015
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