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IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF DELAWARE TAKEDA PHARMACEUTICAL COMPANY, LTD., and TAP PHARMACEUTICAL PRODUCTS INC., Plaintiffs and Counterclaim-Defendants, v. TEVA PHARMACEUTICALS USA, INC., and TEVA PHARMACEUTICAL INDUSTRIES, LTD., Defendants and Counterclaim-Plaintiffs. ) ) ) ) ) ) ) ) ) ) ) ) )

C.A. No. 06-033-SLR REDACTED PUBLIC VERSION

ANSWERING POST-TRIAL BRIEF OF DEFENDANTS TEVA PHARMACEUTICALS USA, INC. AND TEVA PHARMACEUTICAL INDUSTRIES LTD. REGARDING NONINFRINGEMENT OF THE `321 PATENT YOUNG CONAWAY STARGATT & TAYLOR LLP Josy W. Ingersoll (No. 1088) [[email protected]] Karen L. Pascale (No. 2903) [[email protected]] Karen E. Keller (No. 4489) [[email protected]] The Brandywine Building 1000 West St., 17th Floor P.O. Box 391 Wilmington, Delaware 19899-0391 Phone: 302-571-6600 SUTHERLAND ASBILL & BRENNAN LLP John L. North Jeffrey J. Toney Jeffrey D. Blake Laura Fahey Fritts 999 Peachtree Street Atlanta, Georgia 30309-3996 Phone: 404-853-8000 Attorneys for Defendants, Teva Pharmaceuticals USA, Inc and Teva Pharmaceutical Industries, Ltd. January 10, 2008

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TABLE OF CONTENTS TABLE OF AUTHORITIES ...................................................................................................... ii I. II. EXECUTIVE SUMMARY ............................................................................................. 1 PERTINENT LEGAL STANDARDS............................................................................. 4 A. B. The Hatch-Waxman Act Permits Challenges to Drug Patents .............................. 4 The Court First Construes the Patent Claims........................................................ 5 1. 2. 3. 4. 5. C. III. The Court Construes All Limitations of the Asserted Claims.................... 5 The Claim Language Must Be Read As a Whole...................................... 5 The Claim Must Be Construed From the Perspective of a Person of Ordinary Skill in the Art ("POSITA"). ..................................................... 5 The Claims Should Be Construed in Light of the Specification; Dictionaries and Other Extrinsic Evidence Are Disfavored. ..................... 6 The Patent Must Give "Public Notice" of Its Metes and Bounds. ............. 7

Plaintiffs Bear the Burden of Proving That Teva's Product Embodies Every Claim Limitation ....................................................................................... 7

TEVA DOES NOT INFRINGE THE `321 PATENT ...................................................... 8 A. B. The Asserted Claim 2 Includes Six Limitations ................................................... 8 The "In Contact . . . Evenly" Limitation Requires Uniform Physical Mixing ................................................................................................................ 8 1. Claim Construction: "In Contact . . . Evenly" Requires Physical, Homogenous Mixing. .............................................................................. 8 a) The Intrinsic Evidence Requires Physical Contact Through a Homogenous Mixture of the Lansoprazole and Magnesium Carbonate.................................................................. 9 (1) The Inventors Described the Invention To Be a "Homogenous Mixture" During Prosecution to Distinguish Prior Art......................................................... 9 The Specification Describes the Invention To Be a Homogenous Mixture ..................................................... 12

(2)

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(3) (4)

"Homogenous Mixture" Describes the Final Product; It Is Not a Process Limitation............................ 14 In The Art, a "Homogenous Mixture" Need Only Be "Uniform"; Each Particle Need Not Be In Contact. .......................................................................... 15

b)

The Intrinsic Record Contradicts Plaintiffs' Construction. .......... 16 (1) (2) Plaintiffs Offer No Meaning for the Term "Mixture" ....................................................................... 16 The Intrinsic Record Fails to Support a "Uniformly Basic Environment" Interpretation of "In Contact . . . Evenly." ....................................................... 16

c)

The Court Should Not Consider Plaintiffs' Extrinsic Evidence .................................................................................... 18 (1) The Court Should Not Resort to Extrinsic Evidence When the Intrinsic Evidence Unambiguously Defines the Limitations................................................... 18 Dr. Byrn's Proton Transfer Theory Was Not Disclosed In His Expert Report, Would Have Been Rejected By a POSITA, And Is Wrong ........................... 18 Plaintiffs' Dictionary Definitions Are Extrinsic Evidence Taken Outside the Context of the Patents and Should Not Be Considered ....................................... 20 The Litigation Testimony of Takeda Inventors Should Be Given No Weight........................................... 20

(2)

(3)

(4) C.

Teva's Product Does Not Infringe: The Lansoprazole and Magnesium Carbonate Are Not "In Contact . . . Evenly" ...................................................... 20 1. 2. Summary: Teva Designed Around the `321 Patent By Formulating Its Product in Layers. ............................................................................. 20 Teva's ANDA Specifies a Layered Formulation Separating the Lansoprazole and Magnesium Carbonate ............................................... 22 a) b) Teva's ANDA Specifies a Layered Formulation. ........................ 22 Teva's Final Product Is A Layered Formulation In Which The Lansoprazole And Magnesium Carbonate Are Separate, Not Homogenously Mixed. ......................................... 23 ii

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c) 3.

Teva's Talc Subcoat Forms a Separating Layer. ......................... 25

Chemical Analysis Establishes That Teva's ANDA Product Does Not Contain an Infringing Mixture of Lansoprazole and Magnesium Carbonate. .......................................................................... 26 a) b) Summary: Teva Presented Unbiased, "Blinded" Chemical Analysis to Determine Infringement.. ......................................... 26 ToF-SIMS Confirms That Teva's Product Does Not Have a Homogenous Mixture................................................................. 28 (1) (2) ToF-SIMS Is the Superior Technique for Surface Analysis.......................................................................... 28 The ToF-SIMS Data Shows That Lansoprazole and Magnesium Carbonate in Teva's Product Are Separated, Not Mixed ..................................................... 30 Peer-Reviewed Literature ­ Including a Paper By Dr. Bugay Himself ­ Confirms Mr. Hirt's Reliance on ToF-SIMS.................................................................. 31

(3)

c)

Laser Raman and EDS Analysis Confirmed the ToF-SIMS Data. .......................................................................................... 37 (1) (2) (3) Sample Preparation: Mr. Hirt Properly Prepared Samples for Analysis; Plaintiffs Did Not......................... 37 Laser Raman Data Confirmed the ToF-SIMS Results............................................................................ 41 The EDS Data Confirms That Teva's ANDA Product Does Not Contain a Homogenous Mixture ......... 43

d) e) f)

Plaintiffs Adduced No Evidence in Support of Their "Uniform Basic Environment" Construction............................... 45 Plaintiffs Adduce No Evidence for Their New "Proton Transfer" Theory. ....................................................................... 47 Plaintiffs Cannot Meet the Burden of Proving the "In Contact . . . Evenly" Limitation Merely By Showing That Teva'e Product Is Stable............................................................. 51 Plaintiffs Cannot Base Their Infringement Case on Evidence of Teva's Prior, Discarded Formulations. .................... 52

g)

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D.

Plaintiffs Failed to Prove Teva's Product Meets Other Claim Limitations.......... 53 1. 2. 3. "Pharmaceutical Composition". ............................................................. 53 "Wherein the Composition is Made Up Into Tablets or Granules and Then Coated by a Coating Agent. .................................................... 54 "Amount of the Basic Inorganic Salt Relative to Parts by Weight of the Benzimidazole Compound Being About 0.3 ­ 20 Parts by Weight". ................................................................................................ 54

IV. V.

PLAINTIFFS ARE NOT ENTITLED TO THE INJUNCTIVE RELIEF REQUESTED............................................................................................................... 55 CONCLUSION............................................................................................................. 59

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TABLE OF AUTHORITIES CASES Abbott Labs. v. Novopharm Ltd., 323 F.3d 1324, (Fed. Cir. 2003) ............................................................................... 5, 53 Abbott Labs. v. TorPharm, Inc., 503 F.3d 1372 (Fed. Cir. 2007) ..................................................................................... 58 Acumed LLC v. Stryker Corp., 483 F.3d 800 (Fed. Cir. 2007) .................................................................................12, 13 AFG Indus. Inc. v. Cardinal IG Co., 375 F.3d 1367 (Fed. Cir. 2004) ..................................................................................... 14 AFG Indus. Inc. v. Cardinal IG Co., 224 Fed. Appx. 956 (Fed. Cir. March 30, 2007) .......................................................14, 15 Apotex, Inc. v. Thompson, 347 F.3d 1335 (Fed. Cir. 2003) ...................................................................................... 4 Aquatex Indus., Inc. v. Techniche Solutions, 479 F.3d 1320 (Fed. Cir. 2007) ...................................................................................... 7 Baxa Corp. v. McGaw, Inc., 981 F. Supp. 1348 (D. Colo.1997); aff'd per curiam, 185 F.3d 883 (Fed. Cir. 1999) (unpublished table decision) ................................................................ 52 Biovail Corp. Int'l v. Andrx Pharms., Inc., 239 F.3d 1297 (Fed. Cir. 2001) ...................................................................................... 7 Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 68 F. Supp. 2d 508 (D.N.J. 1999).................................................................................. 19 Centricut, LLC v. Esab Group, Inc., 390 F.3d 1361 (Fed. Cir. 2004) ...................................................................................... 5 Dow Chem. Co. v. Sumitomo Chem. Co., 257 F.3d 1364 (Fed. Cir. 2001) .................................................................................... 13 eBay Inc., v. MercExchange, LLC, 126 S. Ct. 1837 (2006) .................................................................................................. 56 Exxon Chem. Patents, Inc. v. Lubrizol Corp., 64 F.3d 1553 (Fed. Cir. 1995) ........................................................................................ 5

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Glaxo Group Ltd. v. Apotex, Inc., 376 F.3d 1339 (Fed. Cir. 2004) ..................................................................................... 58 Hockerson-Halberstadt, Inc. v. Avia Group Int'l, Inc., 222 F.3d 951 (Fed. Cir. 2000) ........................................................................................ 7 Hutchins v. Zoll Med. Corp., 492 F.3d 1377 (Fed. Cir. 2007) ....................................................................................... 8 Merck & Co., Inc. v. Apotex, Inc., 488 F. Supp. 2d 418 (D. Del. 2007) .......................................................................... 4, 55 MicroStrategy, Inc.v. Business Objects, S.A., 429 F.3d 1344 (Fed. Cir. 2005) ....................................................................................... 8 Network Commerce, Inc. v. Microsoft Corp., 422 F.3d 1353 (Fed. Cir. 2005). ...................................................................................... 8 Pause Tech. LLC v. TiVo Inc., 419 F.3d 1326 (Fed. Cir. 2005) ....................................................................................... 5 Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) ............................................................................6, 13, 20 PSC Computer Prods., Inc. v. Foxconn Int'l, 355 F.3d 1353 (Fed. Cir. 2004) ....................................................................................... 7 Safas Corp. v. Etura Premier, L.L.C., 293 F. Supp. 2d 436 (D. Del. 2003)................................................................................. 9 Southwall Techs., Inc. v. Cardinal IG Co., 54 F.3d 1570 (Fed. Cir. 1995) ....................................................................................... 11 Spring Window Fashions LP v. Novo Indus., L.P., 323 F.3d 989 (Fed. Cir. 2003) ......................................................................................... 7 Standard Oil Co. v. American Cyanamid Co., 774 F.2d 448 (Fed. Cir. 1985) ......................................................................................... 6 TorPharm, Inc. v. Ranbaxy Pharms., Inc., 336 F.3d 1322 (Fed. Cir. 2003) ..................................................................................... 14 Vitronics Corp. v. Conceptronic, Inc, 90 F.3d 1576 (Fed. Cir. 1996) ..................................................................................18, 20 Whittaker Corp. v. UNR Indus., Inc., 911 F.2d 709 (Fed. Cir. 1990) ....................................................................................... 14

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Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339 (Fed. Cir. 2000) ..................................................................................... 58 STATUTES 21 C.F.R. § 314.125(a), (b)(1) (2007) ....................................................................................... 51 35 U.S.C. § 271(3)(4)(B) .......................................................................................................... 56 35 U.S.C. § 271(e)(2) ............................................................................................................. 4, 5 35 U.S.C. § 285 ........................................................................................................................ 58 RULES FED. R. CIV. P. 26(a)(2)(B) ....................................................................................................... 18 FED. R. EVID. 402 ..................................................................................................................... 53 BOOKS, TREATISES AND OTHER SOURCES Webster's New Collegiate Dictionary 713 (1977) ..................................................................... 20 Webster's New Millennium Dictionary of English, Preview Edition (v. 0.9.7) .......................... 15

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Defendants and Counterclaim-Plaintiffs Teva Pharmaceuticals USA, Inc. and Teva Pharmaceutical Industries Ltd. (collectively "Teva") respectfully submit this response to Plaintiffs Takeda's and TAP's Opening Post-Trial Brief Concerning Infringement of the `321 Patent (D.I. 163). I. EXECUTIVE SUMMARY Plaintiffs urge a construction of the critical "in contact . . . evenly" limitation that is nothing short of extraordinary. Plaintiffs ask the Court to construe "in contact . . . evenly" such that the limitation requires no physical contact between magnesium carbonate and lansoprazole. Plaintiffs assert that the claim limitation is met whenever the dosage form has a uniform "basic" or "alkaline" environment, irrespective of where the lansoprazole and magnesium carbonate may be found. This argument is wholly unsupported by the patent specification or the law. It also begs the (factual) question: "What evidence proves a `basic' environment in Teva's product?" The answer: none. Plaintiffs concede that they never tested the pH of a single sample of Teva's ANDA product. So Plaintiffs ask the Court to infer such an environment, invoking analogies of cell phone systems and a new "proton transfer" theory presented only at trial. Teva respectfully submits that the trial evidence, when viewed in context of a proper construction of the claim limitations at issue, establishes that Plaintiffs' infringement arguments fail. Claim construction: With respect to the construction of the "in contact . . . evenly" limitation, the inventors plainly advised the public what that term meant: a homogenous mixture of the lansoprazole and magnesium carbonate. The specification specifically states that the invention must be prepared through "homogenously admixing" the ingredients. In each

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example, the ingredients are physically mixed. And the file history contains references showing that "even" and "homogenous" are interchangeable terms in the context of the alleged invention. There is no indication in the patent or file history ­ and absolutely no notice to the public ­ that the inventors intended to claim a pharmaceutical composition without physical contact between the lansoprazole and magnesium carbonate. Infringement evidence: With respect to infringement, Plaintiffs failed to provide credible evidence that Teva's ANDA product contains the requisite homogenous mixture. It does not. Indeed, Plaintiffs' initial expert report of Dr. Bugay expressly described the Teva product as having layers. (Bugay Tr. at 261, ll. 17-19 ("Q. So when you wrote your report you referred to them as layers; is that right? / A. That general feature, yes.").) Plaintiffs since changed their theories. Plaintiffs now rely on Dr. Byrn's theory that the components in Teva's product accidentally mix during manufacturing. This is supported by nothing but the ipse dixit of Dr. Byrn, who admitted having only one prior experience with subcoats. This accidental mixing theory also was contradicted by the testimony of Teva's expert Dr. Chambliss,1 who has decades of private industry experience making drugs with subcoats. The Court received considerable evidence regarding the different tests the parties performed and the spatial relationship of the lansoprazole and magnesium carbonate in Teva's

1

Dr. Chambliss is a Professor of Pharmaceutics, the Director of Technology Management, and a Research Professor for the National Center for Natural Products Research at the University of Mississippi. He holds a B.S. in Pharmacy, a M.S. in Pharmaceutics, and a Ph.D. in Pharmaceutics. Dr. Chambliss, a drug formulator, has worked in formulation and process development throughout his career. Over his 17 years of private industry experience, Dr. Chambliss held positions at G. D. Searle, BristolMyers, and Schering-Plough where he performed hands-on formulation of granules and pellets with coatings and subcoatings and prepared NDAs and ANDAs for submission to the Food and Drug Administration. At Bristol-Myers, he also gained extensive experience formulating acid sensitive compounds. (Id. at 449, ll. 5-22.) Dr. Chambliss has developed or supervised the development of over 300 pharmaceutical products for the U.S. and international markets. (Chambliss Tr. at 446-52; see also DTX30, attached as Exhibit 1.)

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ANDA product. Teva respectfully submits that its testing, including testing performed by the only "blinded" expert to appear before the Court, supports the ANDA's description of a layered product in which the lansoprazole and magnesium carbonate are never mixed, but rather are applied in different layers and further separated by yet another layer of talc. This evidence refutes any argument that the ANDA product contains a homogenous mixture of the lansoprazole and magnesium carbonate. Further, key trial admissions by both Dr. Bugay and Dr. Byrn establish that Plaintiffs failed to meet their burden of proof. Both Dr. Bugay and Dr. Byrn admitted that they could not quantify their test results. Although they used qualitative terms such as "substantial" and "significant" to describe the alleged degree of mixing and contact, they could not tell the Court how much lansoprazole and how much magnesium carbonate were present in any given area of Teva's ANDA product. In other words, there is no proof that any "contact" is "even." As Dr. Byrn testified: Q. And so under your theory, there is a uniform basic environment in all portions of the granule, but you can't tell us in any particular portion of the granule how much magnesium carbonate and how much lansoprazole you have; correct? Correct.

A.

(Byrn Tr. at 168, l. 22 ­ 169, l. 2.) Dr. Bugay made similar admissions: Q. As a result, I mean none of the techniques you used report how much mixing occurred, do they? They do not.

A.

(Bugay Tr. at 257, ll. 15-17.) Without quantification, Plaintiffs cannot prove by a preponderance of the evidence that Teva's ANDA product meets any reasonable construction of the "in contact . . . evenly"

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limitation. And Plaintiffs must prove literal infringement, as they have presented no trial evidence or argument regarding infringement under a doctrine of equivalents theory. Below, Teva briefly will outline the legal standards governing the infringement issues. (See Section II below.) Then it will address the limitations of claim 2 of the `321 patent that are at issue, beginning with the "in contact . . . evenly" limitation. (See Section III below.). II. PERTINENT LEGAL STANDARDS A. The Hatch-Waxman Act Permits Challenges to Drug Patents

Plaintiffs assert claims of infringement under Section 271(e)(2) of the Patent Code. 35 U.S.C. § 271(e)(2). The Hatch-Waxman Act, which gave rise to Section 271(e)(2), permits generic versions of previously approved innovator drugs to be marketed without requiring the submission of a New Drug Application ("NDA"). Apotex, Inc. v. Thompson, 347 F.3d 1335, 1338 (Fed. Cir. 2003); Merck & Co., Inc. v. Apotex, Inc., 488 F. Supp. 2d 418, 420-21 (D. Del. 2007). Instead, a generic version of an approved innovator drug can be marketed after submission of an Abbreviated New Drug Application ("ANDA"), which can rely on testing submitted during the NDA process and a previous FDA finding that the drug is safe and effective. Merck, 488 F. Supp. 2d at 421. Hatch-Waxman gives a generic drug manufacturer an opportunity to challenge infringement and/or the validity of a patent covering an approved innovator drug by making a "Paragraph IV certification." A Paragraph IV certification permits a generic drug manufacturer to market a generic version of the drug before expiration of the challenged patents. In this case, Teva certified under Paragraph IV that the formulation it designed for its ANDA product would not infringe the `321 patent and that the `321 patent is invalid.

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B.

The Court First Construes the Patent Claims 1. The Court Construes All Limitations of the Asserted Claims

The starting point for any patent infringement case, including a case under Section 271(e)(2), is the construction of the claim(s) at issue. Abbott Labs. v. Novopharm Ltd., 323 F.3d 1324, 1329 (Fed. Cir. 2003). Plaintiffs then must show that the ANDA product at issue meets every limitation of the asserted claim(s). Id. Plaintiffs bear the burden of proving infringement by a preponderance of the evidence. Centricut, LLC v. Esab Group, Inc., 390 F.3d 1361, 1367 (Fed. Cir. 2004). Claim construction is a matter of law for the Court. Exxon Chem. Patents, Inc. v. Lubrizol Corp., 64 F.3d 1553, 1556 (Fed. Cir. 1995). Teva set forth the current claim construction standards in its pre-trial claim construction brief. (DI 131.) Plaintiffs do not dispute these general legal standards. Teva highlights below certain specific legal points applicable to the limitations at issue here. 2. The Claim Language Must Be Read As a Whole

Claim limitations must be construed in light of the claim language as a whole. Pause Tech. LLC v. TiVo Inc., 419 F.3d 1326, 1331 (Fed. Cir. 2005). Plaintiffs' attempts to isolate certain words and phrases for construction outside the context of the language of the entire claim are legally invalid. (See, e.g., subsection IV.D(1) below regarding "Pharmaceutical Composition"; see, e.g., Plaintiffs' cell phone analogy.) 3. Claims Must Be Construed From the Perspective of a Person of Ordinary Skill in the Art ("POSITA")

With respect to the `321 patent, which is directed to a homogenously mixed formulation, Plaintiffs' expert Dr. Byrn testified that a "person of ordinary skill is a person with a Bachelor's

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degree in chemistry or pharmacy and two to five years experience in a relevant field."2 (Byrn Tr. at 102, 1. 24 ­ 103, l. 1.) Dr. Byrn and Dr. Bugay have considerably more education and experience ­ indeed, every single witness to testify at trial, both experts and fact witnesses, had considerably more education and experience. The relevant inquiry for claim construction does not take into account extraordinary theories such as Dr. Byrn's late-disclosed "proton transfer" theory, but the view of a POSITA when reading the patent and file history. Standard Oil Co. v. American Cyanamid Co., 774 F.2d 448, 454 (Fed. Cir. 1985) ("A person of ordinary skill in the art is . . . presumed to be one who thinks along the line of conventional wisdom in the art and is not one who undertakes to innovate . . . by extraordinary insights."). 4. The Claims Should Be Construed in Light of the Specification; Dictionaries and Other Extrinsic Evidence Are Disfavored

The Federal Circuit has re-affirmed the primacy of the specification in claim construction. See Phillips v. AWH Corp., 415 F.3d 1303, 1315 (Fed. Cir. 2005). The Phillips decision noted that claim construction had become a battle of competing dictionary definitions, and instructed that less significance should be placed on such extrinsic evidence because it "focuses the inquiry on the abstract meaning of words rather than on the meaning of claim terms within the context of the patent." Id. at 1321. Thus, abstractions and incongruous analogies ­ like comparing a drug to a cell phone system ­ cannot prevail over definitions rooted in the context of the specification.

2

Teva will accept this definition of POSITA with respect to the `321 patent for purposes of this case only.

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5.

The Patent Must Give "Public Notice" of Its Metes and Bounds

The grant to a patent holder of the right to exclude is based on the patent holder's public disclosure of the metes and bounds of the invention. See PSC Computer Prods., Inc. v. Foxconn Int'l, 355 F.3d 1353, 1359 (Fed. Cir. 2004). The Federal Circuit underscores that claim language "must [also] be read consistently with the totality of the patent's applicable prosecution history." Biovail Corp. Int'l v. Andrx Pharms., Inc., 239 F.3d 1297, 1301 (Fed. Cir. 2001). The prosecution history "constitutes a public record of the patentee's representations concerning the scope and meaning of the claims, and competitors are entitled to rely on those representations when ascertaining the degree of lawful conduct, such as designing around the claimed invention." Hockerson-Halberstadt, Inc. v. Avia Group Int'l, Inc., 222 F.3d 951, 957 (Fed. Cir. 2000). "The public notice function of a patent and its prosecution history requires that a patentee be held to what he declares during the prosecution of his patent." Spring Window Fashions LP v. Novo Indus., L.P., 323 F.3d 989, 995 (Fed. Cir. 2003). Teva properly relied on the inventors' representations made in the specification and file history when designing its own formulations to avoid the (properly construed) claims of the `321 patent; Plaintiffs' new "cell phone" and "proton transfer" theories played no role in prosecution of the patent and should have none here. C. Plaintiffs Bear the Burden of Proving That Teva's Product Embodies Every Claim Limitation.

Plaintiffs must establish literal infringement by Teva. Plaintiffs neither argued infringement under the doctrine of equivalents at trial nor submitted any evidence of equivalents, and therefore waived any such claim. Aquatex Indus., Inc. v. Techniche Solutions, 479 F.3d 1320, 1329 (Fed. Cir. 2007) (requiring particularized testimony to a jury or other fact finder, on a limitation-by-limitation basis, describing the claim limitations and establishing that those skilled

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in the art would recognize the equivalents); Network Commerce, Inc. v. Microsoft Corp., 422 F.3d 1353, 1363 (Fed. Cir. 2005). To prove literal infringement, Plaintiffs must demonstrate that the accused product embodies each and every element and limitation of the asserted claim. Hutchins v. Zoll Med. Corp., 492 F.3d 1377, 1380 (Fed. Cir. 2007). Literal infringement cannot be found if "even one [asserted] claim limitation is missing or not met" by the allegedly infringing product. MicroStrategy. Inc. v. Business Objects, S.A., 429 F.3d 1344, 1352 (Fed. Cir. 2005). Teva therefore focuses on Plaintiffs' failure to prove that the Teva ANDA product meets the "in contact . . . evenly" limitation; Teva briefly establishes below that Plaintiffs' proof fails with respect to other limitations as well. III. TEVA DOES NOT INFRINGE THE `321 PATENT A. Asserted Claim 2 Includes Six Limitations

Plaintiffs assert only claim 2 of the `321 patent, and correctly parse the claim into six limitations. (DI 163 at 2-3.) Teva does not dispute that its ANDA product meets the third and fourth limitations regarding the presence of an effective amount of lansoprazole and the presence of magnesium carbonate; Teva's product, however, does not embody the four remaining limitations. Both parties focus on the sixth limitation, which requires that the lansoprazole and magnesium carbonate be "in contact . . . evenly." B. The "In Contact . . . Evenly" Limitation Requires Uniform Physical Mixing 1. Claim Construction: "In Contact . . . Evenly" Requires Physical, Homogenous Mixing

Plaintiffs propose that the Court should construe the "in contact . . . evenly" limitation to mean "a mixture of the benzimidazole compound in contact with the basic (i.e., alkaline) inorganic salt in a uniformly basic environment." (DI 133 at 14.) The intrinsic record, however,

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compels a different construction: that "the benzimidazole compound and the inorganic salt are mixed homogenously together." (DTX734.) As addressed in Teva's pre-trial claim construction briefs (DI 131; DI 140) and further addressed below, the heavy weight of the intrinsic evidence supports Teva's proposed construction. a) The Intrinsic Evidence Requires Physical Contact Through a Homogenous Mixture of the Lansoprazole and Magnesium Carbonate (1) The Inventors Described the Invention To Be a "Homogenous Mixture" During Prosecution to Distinguish Prior Art

The parties agree that the phrase "in contact . . . evenly" was not a term of art at the time Takeda filed for the `321 patent. Thus, Takeda's use of the phrase in the intrinsic record controls construction. Safas Corp. v. Etura Premier, L.L.C., 293 F. Supp. 2d 436, 438 (D. Del. 2003) (noting that the intrinsic record, including the claims themselves, is "of prime importance when claim language has no ordinary meaning in the pertinent art"). The intrinsic record clearly establishes the context and meaning of both the term "contact" and the term "evenly." The inventors specifically describe the "the composition of the invention" as follows: The composition of the invention is prepared by homogenously admixing the above benzimidazole compound, the basic inorganic salt of magnesium and/or basic inorganic salt of calcium, and the above additives. (PTX3 at col. 9, ll. 45-48 (emphasis added).) This is not a description of just one embodiment. It unambiguously states a requirement "of the invention." The entirety of the `321 patent file history likewise underscores the importance of the "in contact . . . evenly" limitation. The inventors repeatedly explain why the claimed technology requires sufficient mixing of the benzimidazole and the basic inorganic salt to achieve an "even distribution" or "homogenous mixture." Indeed, as originally filed, the claims of the `321 patent 9
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lacked the "in contact . . . evenly" limitation. (PTX4, Patent Application, at Takeda 739470739472.) Instead, the as-filed claims merely required the presence of the benzimidazole and a basic inorganic salt of magnesium and/or calcium. (Id. at Takeda 739470.) Takeda added the "in contact . . . evenly" limitation through amendment and in response to an Office Action rejecting the patent claims for obviousness. (DTX4, see claim 19, Amendment, at Takeda 739670-739671.) Amongst other things, the examiner had rejected the application as obvious because the prior art also taught the use of basic inorganic salts to be "old stabilizing agents." Takeda amended its claims to avoid the prior art cited by the examiner. (DTX4, Amendment, at Takeda 739670-739676.) Takeda then differentiated its claimed technology from the examiner-cited references based on the extent of contact required between the benzimidazole and inorganic basic salt in its amended claims. However, the [Rainer] reference makes no comment or suggestion on stabilization of the benzimidazole compounds by contacting with magnesium aluminate or any other basic inorganic salt of magnesium and calcium evenly. It should be noted that in Rainer, et al., magnesium aluminate is contained in the pharmaceutical formulations as an antacid, and in such use as an antacid, the salt need not contact the benzimidazole compounds at all. (Id. at Takeda 739674 (emphasis added).)3 Takeda also submitted a declaration from a named inventor, Dr. Shin-ichiro Hirai, to support patentability of its claimed technology. Takeda submitted the declaration to show that following the criteria set forth in U.S. Pharmacopeia (21st Revision) would result in "an even or homogenous mixture." (Id. at Takeda 739674-739675.) Thus, the contemporaneous

3

The Rainer reference cited by the Examiner during prosecution is U.S. Patent No. 4,686,230. (DTX016.) Defendants' Opening Brief discusses the Rainer reference as part of its obviousness case. The patent teaches a formulation of a benzimidazole and antacids, but does not disclose how the benzimidazole and antacids should be physically incorporated into the formulation. (Id. at col. 40, ll. 2228.) It is undisputed that magnesium carbonate acts as an antacid. (Chambliss Tr. at 504, ll. 2-11.)

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submissions of one of the inventors confirms the interchangeability of the concepts of "even" and "homogenous." Ultimately, Takeda was unable to convince the examiner of the patentability of the claimed technology and was forced to appeal its patentability. (PTX4, Appeal Br. at Takeda 739749-739758.) On appeal, Takeda continued to assert that its claimed technology required sufficient mixing to obtain even contact. (Id. at Takeda 739755.) Explaining the patentability of the claimed technology, Takeda argued that "[n]o evidence of record suggests why one of ordinary skill would infer that the Rainer et al. antacids should be mixed evenly with the benzimidazole derivatives." (Id. (emphasis added).) "Rainer et al. fails to indicate that the benzimidazole derivatives should be mixed at all, much less mixed to the extent that even contact is present." (Id. at Takeda 739757 (emphasis added).) Takeda on appeal again relied on the Hirai declaration to support patentability. "The experimental results reported therein demonstrate the importance of establishing even contact. Inadequate mixing, resulting in uneven contact, yielded unstable products. On the other hand, the products with even contacting showed stability." (Id. (emphasis added).) Takeda ultimately prevailed on appeal, and the `321 patent issued. It cannot now claim that the invention covers combinations of lansoprazole and magnesium carbonate that are not "an even or homogenous mixture." Southwall Techs., Inc. v. Cardinal IG Co., 54 F.3d 1570, 1576 (Fed. Cir. 1995) ("Claims may not be construed one way in order to obtain their allowance and in a different way against accused infringers.").

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(2)

The Specification Describes the Invention As a Homogenous Mixture

Plaintiffs attempt to bypass the specification's description of the invention as a homogenous mixture (see supra) by arguing that this point is contradicted by other portions of the specification. (DI 163 at 26-27.) Plaintiffs rely on the following passage: The method of admixing is optional if the benzimidazole compound can finally be in contact with the basic inorganic salt of magnesium and/or of calcium evenly. Thus, for example, the additives may be admixed with a mixture of the benzimidazole compound and the basic inorganic salt of magnesium and/or calcium as prepared by preliminary admixing, or the basic inorganic salt of magnesium and/or calcium may be added to a mixture of the benzimidazole compound and the additives as prepared by preliminary admixing. (PTX3, col. 9, ll. 56-66 (emphasis added).) This passage in no way negates the notion that the resulting admixture must be homogenous. To the contrary, this language expressly states that the result must be "in contact . . . evenly," and that is precisely what the inventors previously had defined to be a "homogenous mixture" in the context of the invention. The above passage simply stands for the unremarkable proposition that one can implement the invention through a number of methods of mixing and by adding the ingredients in a number of different sequences. Dr. Chambliss explained that a number of different methods for mixing pharmaceutical ingredients was known at the time. (Chambliss Tr. at 481, ll. 4-22.) While the method of mixing may vary, even Dr. Byrn conceded that there is physical mixing in every single example in the specification. (Byrn Tr. at 157, ll. 19-22.) Plaintiffs rely on a recent Federal Circuit case, Acumed LLC v. Stryker Corp., 483 F.3d 800 (Fed. Cir. 2007), for the proposition that the use of both "in contact . . . evenly" and "homogenous mixture" in the specification "is consistent with there being `different meanings of those phrases.'" (DI 163 at 25.) While Plaintiffs accurately recite the stark holding in Acumed, a more thorough reading reveals that Acumed is quite different from the case at hand. There, the

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court attempted to determine whether the plaintiff's use of "perpendicular" in the specification equated to its use of "transverse" in claim language. Acumed, 483 F.3d at 807. The court ultimately decided that the ordinary meaning of "transverse" did not imply "perpendicular" because "there [was] very little indication that the patentees considered perpendicularity important to their invention." Id. In addition, the Acumed court noted that "perpendicular hole[s] . . . may not always be ideal." Id. at 807. In contrast, Takeda repeatedly emphasized the importance of a homogenous mixture in its final product. (See PTX4, Amendment at Takeda 739674 (noting the need for "an even or homogenous mixture"), and at Takeda 739757 (stating that "[i]nadequate mixing, resulting in uneven contact[] yielded unstable products" while "products with even contacting showed stability").) Further, Takeda clearly stated that homogenous contact is more than ideal ­ it is required for a stable compound. (Id. at Takeda 739674-739675) Thus, just as the intrinsic evidence supported the Acumed conclusion to give "transverse" and "perpendicular" different meanings, the intrinsic evidence in the case requires the opposite result. Plaintiffs also cite Dow Chemical Co. v. Sumitomo Chemical Co., 257 F.3d 1364 (Fed. Cir. 2001). (DI 140 at 5.) Dow, which Teva distinguished during claim construction (see DI 140 at 5), was decided prior to Phillips and is of little value for this analysis. The Dow court started with a technical dictionary definition and referenced intrinsic evidence only to confirm that definition. Id. at 1376-77 (noting that "boiling point" and "reaction temperature" cannot be synonymous because of an inherent technical difference in how they are measured). The parties here agree that the disputed term is not an ordinary term of art and, unlike in Dow, it does not have a universally accepted technical definition. As stated above, the intrinsic evidence in this case, reviewed as instructed by Phillips, cannot sustain the result advocated by Plaintiffs.

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(3)

"Homogenous Mixture" Describes the Final Product; It Is Not a Process Limitation

Plaintiffs suggest that Teva is improperly attempting to read a process limitation into a product claim. (See DI 163 at 25-26.) This is incorrect. Teva's proposed construction simply incorporates what the inventors claimed as the end product ­ a homogenous mixture, not any particular method of mixing. Teva's proposed construction in no way limits the process by which the homogenous mixing must occur. The patent discloses several different types of equipment that could be used ultimately to result in the homogenous mixture. (Chambliss Tr. at 481, ll. 15-22; PTX3, col. 12, l. 55 ­ col. 16, l. 15.) Takeda avoided obviousness objections by repeatedly arguing that sufficient mixing was necessary to obtain even contact and the benefits of the claimed technology. Even if the Court were to view a homogenous mixture to refer not to the final product, but as reading in a process limitation, which is not the case, Teva submits that Takeda's arguments during prosecution of the `321 patent allow a process limitation to be read into the claim. Plaintiffs rely on AFG Indus. Inc. v. Cardinal IG Co. to support their contention that it is "well-established" that process limitations cannot be read into a product claim. 375 F.3d 1367 (Fed. Cir. 2004). Not true. An exception to this general rule arises when the process limitation is argued by the inventors to distinguish prior art: [E]xceptions may arise when the product's distinction from the prior art depends on how it was produced, for when the validity of the patent depends on use of a particular process, the claims are construed in the manner that will sustain their validity, when such construction is supported by the record. AFG Indus. Inc. v. Cardinal IG Co., 224 Fed. Appx. 956, 958 (Fed. Cir. 2007) (citing Whittaker Corp. v. UNR Indus., Inc., 911 F.2d 709, 712 (Fed. Cir. 1990) and TorPharm, Inc. v. Ranbaxy Pharms., Inc., 336 F.3d 1322, 1329 (Fed. Cir. 2003)). The Federal Circuit ultimately found that

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"the process by which a product is produced can limit a product claim when, as here, the process is relied on for patentability and validity." Id. at 958-59. Plaintiffs cannot dispute that Takeda repeatedly argued that the patentability of its technology resulted from "sufficient mixing." As such, Takeda's arguments place construction of this claim term squarely within the exception identified in the second AFG Industries opinion. Therefore, while Teva maintains that its proposed construction refers to the claimed dosage form and does not import a process limitation into a product claim, Takeda's arguments during prosecution would make it proper to do so. (4) In The Art, a "Homogenous Mixture" Need Only Be "Uniform"; Each Particle Need Not Be In Contact

Plaintiffs argue that Teva's proposed construction of "in contact . . . evenly" and definition of "homogenous mixture" contradict the specification, which contains examples where all of the lansoprazole is not touching all of the magnesium carbonate. (See DI 163 at 24.) This is a straw man. Teva never suggests that all of the lansoprazole must be touching all of the magnesium carbonate for there to be a homogenous mixture. To the contrary, Dr. Chambliss testified that the concept of a homogenous mixture was well known by those in the art and understood to mean "uniform." (Chambliss Tr. at 475, ll.17-23; see also Hirai Dep. at 60, ll. 1-11 (defining "homogenous" to mean "well mixed.").) This is consistent with the ordinary meaning of the term "homogenous mixture": "any combination of substances that has uniform composition and properties; a mixture that is uniform throughout." Webster's New Millennium Dictionary of English, Preview Edition (v. 0.9.7), http://dictionary.reference.com/browse/ homogeneous mixture (last visited Jan. 10, 2008). (Attached as Exhibit 2.)

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b)

The Intrinsic Record Contradicts Plaintiffs' Construction

Plaintiffs' proposed construction of "in contact . . . evenly" ­ "a mixture of the benzimidazole compound in contact with the basic (i.e., alkaline) inorganic salt in a uniformly basic environment" ­ finds no support in the patent or file history. (1) Plaintiffs Offer No Meaning for the Term "Mixture"

Plaintiffs pay lip service to the term "mixture" in their construction, but give that term no real meaning. Certainly the description of the requisite "mixture" set forth by Plaintiffs' expert differs substantially from that argued by the inventors during prosecution. Plaintiffs now eschew the standards set forth in the USP, expanding "mixture" to include the presence of only one percent lansoprazole in ninety-nine percent magnesium carbonate without regard to homogeneity. (Bugay Tr. at 258, ll. 1-5.) Put another way, applying Plaintiffs' experts' understanding of mixture, the requisite mixture exists as long as there is an alkaline environment. (See DI 163 at 24.) Plaintiffs no longer believe a true mixture is necessary. (2) The Intrinsic Record Fails to Support a "Uniformly Basic Environment" Interpretation of "In Contact . . . Evenly"

Plaintiffs point to no reference in the file history that supports their "uniformly basic environment" interpretation. There is none. Plaintiffs' references to the specification fare no better. While Plainitiffs attempt to cobble together specification references to water and pH levels, the references provide no support for Plaintiffs' conclusion. With regard to water, the bottom line is that the patent teaches that water is bad because lansoprazole is "susceptible to . . . moisture" and "poor in stability." (PTX3 at col. 1, ll. 33-36.) With respect to the specification's references to pH levels, the statements always refer to the basic nature of the basic inorganic salt of magnesium and/or calcium. (See DI 163) Nowhere in the specification did the inventors use the term "basic" to 16
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describe anything but an basic inorganic salt. (Byrn Tr. at 151, l. 13 ­ 152, l. 6.) While Plaintiffs would like the Court to splice the word "basic" and place it before the word "solution" or "environment," the specification provides no rational basis for doing so. (See DI 163 at 22.) Finally, the Examples teach away from Plaintiffs' proposed claim construction. The granules described in Examples 1, 2, and 7, contain no water. (PTX3 at col. 12, l. 55 ­ col. 13, l. 23 and col. 14, ll. 18-41.) The granules were prepared using a dry granulator. (Id.) Without the addition of water, a "uniform basic environment" and contact through proximity resulting from the proton transfer theory cannot exist. Thus, Examples 1, 2 and 7 do not support Plaintiffs' moisture-driven theory and, in fact, teach away from it. Additional Examples also teach away from Plaintiffs' proposed claim construction. The granules prepared in Examples 3, 4, 5, 6, and 8 all require the addition of a small amount of water. (Id. at col. 13, l. 24 ­ col. 14, l. 15 and col. 14, ll. 45-69.) Each of these Examples, however, require that the mixtures be "dried in vacuum at 40º C for 16 hours" before forming the granule. (Id. (40º C is equivalent to 104º F).)4 The inventors expressly teach that the mixture should be dried after mixing ­ yet again teaching a person of ordinary skill in the art that the amount of water in the formulation should be minimized. As such, Examples 3, 4, 5, 6, and 8 not only fail to support Plaintiffs' moisture driven theory, they teach away from it.

4

At trial, Dr. Byrn dismissed the Examples as teaching a brief amount of drying. Respectfully, 16 hours of drying at over 100 degrees cannot constitute "dry[ing] them briefly." (Byrn Tr. at 97, l. 25 ­ 98, l. 5.)

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c)

The Court Should Not Consider Plaintiffs' Extrinsic Evidence (1) The Court Should Not Resort to Extrinsic Evidence When the Intrinsic Evidence Unambiguously Defines the Limitations

Teva's proposed construction of the "in contact . . . evenly" limitation is supported by the unambiguous teachings of the intrinsic record. Accordingly, there should be no resort to extrinsic evidence. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1583 (Fed. Cir. 1996) ("In most situations, an analysis of the intrinsic evidence alone will resolve any ambiguity in a disputed claim term. In such circumstances, it is improper to rely on extrinsic evidence."). Plaintiffs' extrinsic evidence should be rejected for the following reasons as well. (2) Dr. Byrn's Proton Transfer Theory Was Not Disclosed In His Expert Report, Would Have Been Rejected By a POSITA, And Is Wrong

Teva objected to Dr. Byrn's proton transfer theory for the alleged creation of the uniform basic environment on the basis that such theory had not been disclosed in his expert reports. (Byrn Tr. at 91, ll. 11-16 and 96, ll. 20-24.) Most telling is that, given Teva's objection to this new theory, Plaintiffs fail in their Opening Brief to point to any disclosure in the expert reports that the "in contact . . . evenly" limitation can be met by this "proton transfer" theory. Accordingly, the Court should bar consideration of this late developed theory. See Fed. R. Civ. P. 26(a)(2)(B) (An expert report "must contain . . . a complete statement of all opinions the witness will express and the basis and reasons for them."). Moreover, this theory is irrelevant because there is no evidence that a POSITA reading the `321 patent would have considered that "proton transfer" might render two components of a drug formulation that were not only remote from each other, but in fact separated by an intervening layer, to be "in contact . . . evenly." Without some evidence that a POSITA would

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have appreciated the proton transfer theory, it should not be considered. Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 68 F. Supp. 2d 508, 531 (D.N.J. 1999) ("[E]vidence must be viewed from the position of a person of ordinary skill, not from the position of an expert."). Indeed, the evidence directly contradicted such a conclusion. Dr. Bugay, himself substantially more educated than the POSITA that Dr. Byrn described,5 had not considered the new theory even as of the time he testified at trial. (Bugay at Tr. 278, ll. 4-8.) Finally, for the reasons set forth by Dr. Meyer6 and described below in subsection III.C.(3)(e), Dr. Byrn's proton transfer theory does not hold up under technical scrutiny.7 The foregoing explains why, even after listening to Dr. Byrn's testimony regarding his "proton transfer" theory and having a night to digest it, Dr. Bugay still was unable to explain, comment on, or even support Dr. Byrn's infringement theory. (Bugay Tr. at 277, l. 1 ­ 278, l. 8.)

5

Dr. Byrn testified that a POSITA would have "a bachelor's degree in chemistry or pharmacy and two to five years experience in the relevant field." (Byrn Tr. at 102, l. 24 ­ 103, l. 1.) Dr. Byrn's academic qualifications alone show that he is not a POSITA. 6 Dr. Meyer is a Professor of Chemistry and Materials Science & Engineering at Johns Hopkins University, with a joint appointment in the departments of Chemistry and the department of Engineering. He holds a B.S. in Chemistry and Mathematics from the State University of New York at Albany. He received a Ph.D. in Chemistry from the University of Wisconsin at Madison, where his research focused on analytical and spectroscopic methods. He performed postdoctoral work at the University of North Carolina at Chapel Hill. And Dr. Meyer began teaching at Johns Hopkins in 1991. His research funding includes grants from the National Science Foundation to research the electronic interactions in hybrid organic nanoparticle materials. He also serves as a reviewer and an advisory board member of several journals of the American Chemical Society. (Meyer Tr. at 368-72; see also DTX66.)
7

To the extent that the Court considers Dr. Byrn's late disclosed theory, Teva submits that it also should consider Dr. Meyer's response at trial, and Plaintiffs' motion to strike (see DI 163 at 39-41) should be denied.

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(3)

Plaintiffs' Dictionary Definitions Are Extrinsic Evidence Taken Outside the Context of the Patents and Should Not Be Considered

Plaintiffs rely upon non-technical dictionary terms to support a bizarre "cell phone" analogy to buttress Plaintiffs' proposed claim construction. (See DI 163 at 22-23.) Such dictionary definitions constitute extrinsic evidence. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1584 (Fed. Cir. 1996). Moreover, this is precisely the use of dictionary definitions that the Federal Circuit frowned upon in Phillips. Phillips v. AWH Corp., 415 F.3d 1303, 132122 (Fed. Cir. 2005). These definitions and the cell phone analogy as a whole are completely divorced from the alleged invention at issue and the teachings of the specification. See id. (4) The Litigation Testimony of Takeda Inventors Should Be Given No Weight

Finally, Plaintiffs also rely upon deposition testimony of Takeda inventors in an attempt to support their proposed claim construction. See DI 163 at 6. Inventor testimony is extrinsic evidence. Vitronics, 90 F.3d at 1584. Moreover, hindsight and litigation-oriented testimony such as this should be given no weight. Finally, the testimony on which Plaintiffs rely does not support their moisture driven process: mechanochemical relates to the "conversion of chemical energy into mechanical work" and not contact mediated through water as Plaintiffs state. (Webster's New Collegiate Dictionary 713 (1977), attached as Exhibit 3.) C. Teva's Product Does Not Infringe: The Lansoprazole and Magnesium Carbonate Are Not "In Contact . . . Evenly" 1. Summary: Teva Designed Around the `321 Patent By Formulating Its Product in Layers

Plaintiffs concede that Teva "attempted to design around the `321 Patent by purportedly physically separating lansoprazole and magnesium carbonate in the product." (See DI 163 at 2.) Indeed, Dr. Bugay conceded in his initial expert report ­ drafted as it was before Plaintiffs

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retreated to "accidental mixing" as one of their primary theories ­ that mere optical inspection establishes that Teva's ANDA product contains multiple layers. (See DTX300, attached as Exhibit 4.) Paragraph 37 of that report describes Teva's layered product as follows: 37. A number of features are present in the optical image of the prepared granule surface. First, the cross-sectioned surface of the granule appears as a whitish solid having a generally layered appearance. There appears to be a core located in the center of the granule and a first layer annular to the core. The first layer appears to be approximately 40 ·m in thickness as demonstrated in Exhibit 14 (Bugay 0026). There appears to be a second layer with a slightly darker shade of white within the optical image. Finally, there appears to be a third layer having a slightly whiter shade within the optical image. The three layers are approximately 100 · in thickness and for this particle cross-sectional area of this one granule, it appears that the first and third layers are nearly equivalent in thickness and slightly larger in thickness than the second layer. At the edge of the granule, a fourth layer is slightly visible based upon the darker image in this area. I believe the fourth layer to be the enteric coating of the granule. No smearing of the surface of the granule has occurred due to the sample preparation procedure. (Id. (emphasis added).) At trial, both Dr. Bugay and Dr. Byrn tried to run away from the fact that the Teva product is layered. For instance, on cross examination, Dr. Bugay first tried to refer to the layers as "bars" (Bugay Tr. at 260, ll. 14-17), but then conceded that he considered the product to have "layers" when he drafted his report (Id. at 261, ll. 17-19). Dr. Byrn tried to characterize the layers as "dispersions," but still repeatedly referred to the product's "layers," at least on direct examination. (See, e.g., Byrn Tr. at 122, ll. 7-8 ("And we end up with a layer of talc, hypromellose and lansoprazole").) Mere optical inspection and other strong evidence establish that Teva's product is layered ­ and that Teva applies the lansoprazole and magnesium carbonate in two different layers, separated by yet another layer of talc. Faced with these facts, Plaintiffs sought to avoid the inevitable legal conclusion (that Teva does not infringe) by conjuring a number of novel arguments and theories. Teva addresses these and other pertinent points regarding the "in contact . . . evenly" limitation in the subsections below. 21
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2.

Teva's ANDA Specifies a Layered Formulation Separating the Lansoprazole and Magnesium Carbonate a) Teva's ANDA Specifies a Layered Formulation

Teva's ANDA sets forth the manufacturing process that would be used for commercial production. The multi-step process plainly is aimed at creating a multiple layer product. Teva's ANDA describes the manufacture of Teva's Product, which contains multilayer enteric coated pellets filled into capsules. (Chambliss Tr. at 462, l. 5 ­ 463, l. 10 and 465, l. 24 ­ 467, l. 16; DTX056; DTX303.) Teva's manufacturing process, as described in its ANDA, involves the application of four layers onto sugar spheres to form the multilayer pellet. (DTX056.) Teva applies each of the four layers in a separate manufacturing step. (Id. at TVL006856-99.) Each layer is dried before application of the next layer, a fact that Plaintiffs repeatedly have ignored at trial and in briefing. (Id.) Teva's automated drying process operates in a manner similar to the newer clothes dryers that turn off only when the clothes are dry. (Chambliss Tr. at 470, ll. 1-8.) Teva also includes hypromellose in the dispersion to protect the integrity of each layer. (Id. at 463, ll. 18-23.) Hypromellose is a film former that acts like SaranTM Wrap in protecting the layer from mixing with other layers. (Id.) The multilayer pellets are then filled into capsules to create the final dosage form for administration to patients. (DTX056 at TVL006900-07.) Teva's manufacturing process seeks to minimize the presence of water, rather than encouraging its presence in the final formulation. As stated above, Teva uses its automated drying process to dry its product after application of each and every layer. (Id. at TVL00685699; see also Chambliss Tr. at 468, l. 5 ­ 470, l. 8.) In fact, Teva's ANDA requires that water make up not more than 5.0% of its product, and testing disclosed that water comprised only 1.1% of the final product. (Chambliss Tr. at 465, ll. 3-11; PTX0445A at TVL007539.) In Dr.

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Chambliss' words, a formulation with only 1.1% moisture is "very dry." (Chambliss Tr. at 465, l. 15.) The below demonstrative shows the basic structure of the granule resulting from the above manufacturing process:

(See Chambliss at Tr. 463, l. 11 ­ 467, l. 8.) Dr. Chambliss testified that he had seen NDA and ANDA descriptions such as the above "many times," and there was nothing out of the ordinary about it. (Id. at 467, ll. 17-23 and 474, ll. 12-21.) Dr. Byrn conceded on cross-examination that he had no basis to doubt that Teva can manufacture a pharmaceutical product with an effective subcoat. (Byrn Tr. at 150, ll. 5-9.) b) Teva's Final Product Is A Layered Formulation In Which The Lansoprazole And Magnesium Carbonate Are Separate, Not Homogenously Mixed.

Dr. Bugay's initial report confirmed the layered nature of the ANDA product under visual inspection. (See supra in subsection III.C.(1).) Plaintiffs consequently turned to a number of avoidance arguments including that a two micron talc layer is not thick enough to be a separating layer and the research and development records show this to be the case; there is sufficient water in the manufacturing process to create a mixture and to facilitate Dr. Byrn's proton transfer theory; and the ANDA product is stable and, thus, must meet the "in 23
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contact . . .evenly" limitation. Furthermore, Plaintiffs refused to commit to a single infringement theory in their brief. Plaintiffs argue both that no contact is necessary and that "even contact" can be achieved through their new proton transfer theory, yet Plaintiffs continue to exert substantial effort trying to show that contact is present. None of these arguments stands up under scrutiny, as set forth in the subsections below. When evaluating the manufacturing-related arguments, Teva respectfully submits that the Court should consider the relative experience levels of Dr. Chambliss and Dr. Byrn as it specifically relates to the manufacture of pharmaceutical products that have subcoats. Dr. Chambliss' experience includes 17 years working at G. D. Searle, Bristol-Myers, and ScheringPlough. (Chambliss Tr. at 448, ll. 13-20; see also discussion in note 1.) Dr. Chambliss explained at trial that his substantial industry experience included work on formulations similar to Teva's ANDA product and many formulations that involved the use of subcoats. (Id. at 448, l. 4 ­ 450, l. 24.) Dr. Chambliss also has substantial experience with the machines that make these formulations: "My whole career I've worked with machines that make pharmaceutical products from the mixing of those to the tableting to the pelletization, drying, all the machines." (Id. at 451, l. 23 ­ 452, l. 2.) In stark contrast, Dr. Byrn candidly conceded on cross-examination that he only had one prior work experience relating to subcoats and that was in connection with a litigation: Q. Would you agree with me that the only one work experience you have before this litigation regarding subcoats was another litigation regarding subcoats? Yes.

A.

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(Byrn Tr. at 150, l. 25 ­ 151, l. 3.) Dr. Byrn also conceded that he never has been employed by a pharmaceutical company for the purposes of developing a product with subcoats.8 (Id. at 150, ll. 10-13.) Testing of samples made according to the ANDA process likewise supports the layered nature of the Teva ANDA product. Teva show