Purdue Pharma L.P. v. Teva Pharmaceuticals, USA, Inc. (994 F. Supp. 2d 367, 2014)

FINDINGS OF FACT AND CONCLUSIONS OF LAW

SIDNEY H. STEIN, District Judge.

CONTENTS

TABLE OF ABBREVIATIONS...................................................375

PART 1. INTRODUCTION...................................................376

I.The Record and Relevant Proceedings .................................377

A. The Asserted Patent Claims......................................377

B. The 2012 Ranbaxy Trial..........................................377

C. Claim Construction..............................................378

D. The 2013 Trial..................................................378

E. This Opinion....................................................378

II. Legal Standards.....................................................378

A. Procedural Context and the Hateh-Waxman Act....................378

B. Claims of Patent Infringement....................................379

C. The Affirmative Defense of Patent Invalidity........................380

1. N ovelty and Anticipation........-..............................380

2. Obviousness and Nonobviousness..............................381

3. Written Description and Enablement...........................382

4. Definiteness.................................................383

D. Product>-by-Process Claims ........^.............................383

E. Attorneys Fees .................................................384

PART 2. THE LOW-ABUK PATENTS........................................384

I. Findings of Fact.....................................................384

A. Purdue’s development of low-ABUK oxycodone .....................384

B. Purdue obtains the '799, '800, and '072 Patents......................387

1. The Chapman Application.....................................388

2. Further proceedings before the PTO...........................389

3. The low-ABUK patents-in-suit.................................389

C. The Noramco process............................................391

1. Teva plans to sell tablets containing oxycodone hydrochloride

API and a sustained release carrier..........................391

2. Teva’s tablets contain a non-zero amount of 14-hydroxy...........391

3. 8a forms during the Noramco process..........................392

4. 8a converts to 14-hydroxy during the Noramco process...........393

D. Facts pertinent to obviousness....................................394

1. The ordinary skill in the art is impressive.......................394

2. The prior art disclosed the fact that 8(3 converted to 14-

hydroxy and it disclosed methods of using hydrogenation

to reduce 14hydroxy levels in free base and salt

compositions..............................................395

3. Differences between the prior art and the claims.................397

4. The objective indicia of nonobviousness.........................398

II. Conclusions of Law..................................................401

A. Infringement...................................................401

1. Teva’s ANDA infringes claims 30-34 and 76-79 of the '800

Patent....................................................401

2. Teva’s ANDA infringes claims 1, 4, and 5 of the '072 Patent.....402

3. Teva’s ANDA infringes claims 3 and 19 of the '799 Patent.........402

4. Teva’s use of the Noramco API constitutes an act of

infringement..............................................403

B. Obviousness pursuant to 35 U.S.C. § 103 ...........................403

1. The invention would have been obvious to a skilled artisan........403

2. The asserted claims are invalid pursuant to 35 U.S.C. § 103.....407

C. Invalidity pursuant to 35 U.S.C. § 112 .............................409

1. The written description of the '799, '800, and '072 Patents

satisfies 35 U.S.C. § 112....................................409

2. The patents meet the enablement requirement of 35 U.S.C.

§ 112.60..................................................410

D. Collateral estoppel does not apply.................................411

III. Conclusion..........................................................413

PART 3. THE ABUSE-PROOF PATENTS ....................................413

I. Factual Background: Abuse of OxyContin became tragically rampant,

generating a public health crisis and responses........................413

II. The '383 Patent: Thermoforming Technology...........................416

A. Teva’s ANDA infringes the '383 Patent ............................417

1. Grunenthal’s search for abuse-deterrent formulations led it to

a thermoformed, PEO-based tablet...........................417

2. Teva compresses and then cures its tablets, making them

extremely hard............................................419

3. Comparing Teva’s process to that of the '383 Patent, the

asserted claims read on Teva’s tablets........................419

B. The '383 Patent is invalid as anticipated and obvious.................421

1. The McGinity Application anticipates the '383 Patent.............421

2. At the time of the '383 Patent’s development, the prior art

made the process obvious...................................426

C. Conclusion .....................................................428

III. The '314 Patent: Gel Test Technology .................................428

A. Teva’s ANDA does not infringe the '314 Patent, because Purdue

has not put forward reliable and relevant evidence of

infringement..................................................429

1. Purdue’s evidence of infringement is based on a gel test that

is not designed to replicate the '314 Patent’s gel test.....429

2. Purdue’s evidence of infringement is based on a gel test

conducted in an unreliable manner...........................430

3. To the extent that any experimental evidence is probative, it

suggests that Teva’s tablets do not infringe ...................432

B. The '314 Patent is invalid as indefinite.............................433

1. The “gel test” gives a skilled artisan insufficient guidance to

conduct a replicable experiment .............................433

2. The '314 Patent is both novel and nonobvious....................435

C. Conclusion .................. 437

PART 4. CONCLUSION AND RELIEF.......................................437

TABLE OF ABBREVIATIONS

'072 Patent U.S. Patent No. 7,683,072

'314 Patent U.S. Patent No. 7,776,314

'383 Patent U.S. Patent No. 8,114,383

'799 Patent U.S. Patent No. 7,674,799

'800 Patent U.S. Patent No. 7,674,800

'963 Patent U.S. Patent No. 6,488,963

14-hydroxy 14-hydroxyeodeinone

2013 Stip. Stipulations or Agreed Statements of Fact or Law, Joint Pretrial

Order, Case No. 04 Md. 1603, Dkt. No. 572, filed Aug. 28, 2013

2012 Stip. Stipulations or Agreed Statements of Fact or Law, Joint Pretrial

Order, Case No. 10 Civ. 3734, Dkt. No. 168, filed Oct. 12, 2012

8,14-dihydroxy-7,8-dihydrocodeinone 8,14-dihydroxy

8a, 14-dihydroxy-7,8-dihydrocodeinone 8a

8(3,14-dihydroxy-7,8-dihydrocodeinone 8P

8-acetoxy-14-hydroxydihydrothebaine 8-acetoxy

a,p-unsaturated ketone ABUK

Abbreviated New Drug Application ANDA

active pharmaceutical ingredient API

International Application No. WO 95/20947 Bastin

U.S. Patent No. 7,153,966 Casner

U.S. Patent No. 6,177,567 Chiu

crude oxycodone base COB

Daltons Da

Drug Master File DMF

U.S. Food and Drug Administration FDA

hydrochloride HC1

U.S. Patent No. 4,070,494 Hofftneister

high-performance liquid chromatography HPLC

Newtons N

New Drug Application NDA

osmotieally controlled-release oral delivery system OROS

parts per million ppm

polyethylene oxide PEO

purified oxycodone base POB

U.S. Patent and Trademark Office PTO

Defs.’ Post-Trial Mem. dated Nov. 6, 2013 Teva Mem.

U.S. Provisional Patent Application No. 60/310,534 WrighMDshlack

PART 1. INTRODUCTION

This consolidated trial concerns six patents associated with the pa in reliever OxyContin. Plaintiffs, led by the OxyContin manufacturer Purdue, allege that Teva, which manufactures generic pharmaceutical products, has infringed these patents by seeking approval from the U.S. Food and Drug Administration (“FDA”) to sell bioequivalents of OxyContin. In response, Teva argues that its proposed products do not infringe plaintiffs’ patents and that, in any event, the asserted patents are invalid. These arguments played out over the course of extensive litigation, culminating in a twenty-day-long bench trial before this Court. These findings of fact and conclusions of law are the results of that litigation.

Three patents-in-suiU — United States Patent Nos. 7,674,799 (“the '799 Patent”), 7,647,800 (“the 800 Patent”), and 7,683,072 (“the '072 Patent”) (collectively, “the lowABUK patents”) — recite an improved formulation of oxycodone, the active pharmaceutical ingredient in OxyContin. Those patents describe an oxycodone salt with extremely low levels of a particular impurity, 14-hydroxycodeinone (“14-hydroxy”), which belongs to a class of potentially dangerous compounds known as a,(3-unsaturated ketones (“ABUKs”)). Purdue was the first to succeed in developing a lowABUK oxycodone salt as an active pharmaceutical ingredient (“API”). Its lowAJBUK patents reflect that work.

Also in suit are two patents — United States Patent Nos. 7,776,314 (“the '314 Patent”) and 8,114,383 (“the '383 Patent”) (collectively, “the abuse-proof patents”)— that claim technology making tablets resistant to abuse. The technology disclosed in these patents is intended to hinder would-be abusers from crushing tablets into powder, converting the powder into a liquid, and then injecting the solution intravenously in order to experience an opioid “high.”

The parties in these actions play various roles in the scientific and pharmaceutical communities. Universities provide the infrastructure for the advancement of human knowledge; pharmaceutical manufacturers seeking patents and marketing branded drugs discover new frontiers of medication and health; and generic pharmaceutical companies make those frontiers available to the public. This circle of invention, medicine, health, and profit depends on principles of intellectual property — the law’s allocation of restrictions and liberties.

Applying those principles and the evidence presented at trial, the Court concludes that Teva has not infringed any valid patent asserted by plaintiffs. As explained below, plaintiffs have not carried their burden of proving infringement of the '314 Patent. Although plaintiffs have proved by a preponderance of the evidence that Teva’s proposed products infringe the '799, '800, '072, and '383 Patents, Teva has proved by clear and convincing evidence that the asserted claims of those patents are invalid.

I. The Record and Relevant Proceedings

A. The Asserted Patent Claims

Purdue alleges that Teva’s proposed formulations infringe several claims of the patents-in-suit. In the low-ABUK portion of the trial, Purdue accuses Teva of infringing claims 3 and 19 from the '799 Patent, claims 30-34 and 76-79 from the '800 Patent, and claims 1, 4, and 5 from the '072 Patent. These claims are directed to an oxycodone salt API that contains 14-hydroxy at extremely low levels, and some of the claims specifically refer to an oral dosage form of that API.

In the abuse-proof portion of the litigation, Purdue accuses Teva of infringing claims 1, 2, 5, 7, and 8 from the '383 Patent. These claims describe a thermoformed pharmaceutical dosage form that is so physically hard that it can withstand forces as strong as 500 Newtons (500N) without breaking. Finally, Purdue accuses Teva of infringing claims 1, 2, 6, and 9 from the '314 Patent. These claims relate to a pharmaceutical dosage form that deters abuse by becoming viscous when dissolved in a liquid.

This consolidated litigation also included Purdue’s claims against Impax Laboratories, Inc., and Sandoz Inc., two other generic manufacturers. Impax and Sandoz appeared at trial alongside Teva but have since settled their actions. (See Case No. 11 Civ. 2400, Dkt. No. 147; Case No. 11 Civ. 4694, Dkt. No. 124; Case No. 12 Civ. 5082, Dkt. No. 43.) Purdue asserted claims from one patent — United States Patent No. 6,488,963 (“the '963 Patent”)— against Impax and Sandoz but not against Teva. This Opinion therefore does not address arguments related to the infringement or invalidity of the '963 Patent.

B. The 2012 Ranbaxy Trial

In November and December of 2012, the Court held an eight-day bench trial in Purdue Phrama, L.P., et al. v. Ranbaxy, Inc., et al, No. 10 Civ. 3734(SHS). There, Purdue and its affiliates asserted claims of infringement against Actavis Elizabeth LLC with respect to the low-ABUK patents. Actavis, in turn, presented evidence that the low-ABUK patents were invalid. The parties to the 2012 trial filed a consent judgment on May 1, 2013. That consent judgment provided, inter alia, that “[t]he Low ABUK Patents are valid and enforceable with respect to the Actavis [Abbreviated New Drug Applications] and any products described therein” and “[t]he products described in the Actavis [Abbreviated New Drug Applications] infringe the Low ABUK Patents.” (Case No. 04 Md.1603, Dkt. No. 546¶ 2.) Consequently, no findings of fact or conclusions of law ever emerged from that trial.

The same claims and defenses presented in the 2012 trial are again at issue in this trial, and the parties have agreed to adopt the entire record of the 2012 trial as part of the factual record in this trial. (Supp. to the Joint Pretrial Order Relating to Ranbaxy et al. Trial Record, Case No. 04 Md. 1603, Dkt. No. 582, filed Sept. 13, 2013, at 1 ¶ 1.)

C. Claim Construction

After extensive briefing and a claim construction hearing, this Court issued a Claim Construction Opinion and Order in this matter. See In re OxyContin Antitrust Litigation, 965 F.Supp.2d 420, No. 04 Md. 1603 (SHS), 2013 WL 4509633 (S.D.N.Y. Aug. 23, 2013) (“OxyContin Claim Construction ”). There, the Court construed the patent claims at issue in these actions to the extent the parties disputed the meanings of claim terms. All parties to this trial participated in litigating the claim constructions, so for purposes of this trial that Opinion and Order “define[s] the invention[s] to which the patentee is entitled the right to exclude.” Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed.Cir.2005) (en banc) (quotation marks omitted).

D. The 2013 Trial

The bench trial in the above-captioned matters began on September 23, 2013. The Court heard testimony from 22 witnesses and admitted hundreds of exhibits over the course of more than three weeks. Because of the adoption of the 2012 trial record as part of this trial’s record, the parties focused their presentations on the abuse-proof patents. That said, because Teva was not a party to the 2012 trial, it had (and took advantage of) the opportunity to present additional evidence on the low-ABUK patents.

E.This Opinion

On the basis of the record established by the parties and the applicable law, the Court enters these findings of fact and conclusions of law pursuant to Rule 52(a) of the Federal Rules of Civil Procedure. To the extent that any findings of fact may be deemed conclusions of law, they shall also be considered conclusions of law; to the extent that any conclusions of law may be deemed findings of fact, they shall also be considered findings of fact. See Miller v. Fenton, 474 U.S. 104, 113-14, 106 S.Ct. 445, 88 L.Ed.2d 405 (1985).

II. Legal Standards

A. Procedural Context and the Hatch-Waxman Act

This litigation arises under the Drug Price Competition and Patent Term Restoration Act of 1984, Pub.L. No. 98-417, 98 Stat.1585 (codified at 21 U.S.C. §§ 301 et seq.) (“Hatch-Waxman Act”). The Hatch-Waxman Act provides a streamlined regulatory pathway for generic pharmaceutical companies to seek approval of their drugs, while giving branded pharmaceutical companies an opportunity to sue to defeat approval of the generic drugs.

Under the Hatch-Waxman Act, a pharmaceutical company can seek FDA approval for a generic drug based on an already-approved branded drug by filing an Abbreviated New Drug Application (“ANDA”). 21 U.S.C. § 355©(2)(A), (8)(B). As the name suggests, an ANDA does not require the detailed showings necessary for the pioneer New Drug Application (“NDA”), such as proof of safety and effectiveness. See id. Where a branded manufacturer’s patent has not yet expired but a generic manufacturer nonetheless wants to enter the market, the generic must file a preexpiration challenge (known colloquially as a “Paragraph IV” certification, after the relevant paragraph number in the legislation). Id. § 3S5(j)(2)(A)(vii)(IV). A generic firm’s Paragraph IV certification must establish bioequivalence of the proposed generic version with the approved branded version of the drug. See 21 C.F.R. § 314.94(a)(9). The Paragraph TV certification must also state and explain at least one of the following claims: that the generic product would not infringe the branded firm’s patent, or that the branded firm’s patent is invalid. See 21 U.S.C. § 355(j) (2) (B) (iv) (II).

As the U.S. Court of Appeals for the Second Circuit has explained, the mere filing of “[a]n ANDA-IV certification ... constitutes an act of infringement, triggering the branded manufacturer’s right to sue.” Ark. Carpenters Health & Welfare Fund v. Bayer AG, 604 F.3d 98, 101 (2d Cir.2010) (citing 35 U.S.C. § 271(e)(2)(A)). When a branded manufacturer files suit pursuant to that right within 45 days of receiving notice of the Paragraph IV certification, the litigation automatically stays the generic’s entry to the market. 21 U.S.C. § 355(j)(5)(B)(iii). At its core, then, the Hatch-Waxman Act shifts risks between the patent holder and the generic manufacturer, allowing the generics to challenge the validity of the brands’ patents without incurring either high market entry costs or the risk of damages from infringement. See Ark. Carpenters Health & Welfare Fund, 604 F.3d at 101. More significantly for purposes of this trial, this structure allows the parties to try the dueling issues of patent infringement and patent invalidity at once.

B. Claims of Patent Infringement

“Patent infringement, whether literal or by equivalence, is an issue of fact, which the patentee must prove by a preponderance of the evidence.” Siemens Med. Solutions USA, Inc. v. Saint-Gobain Ceramics & Plastics, Inc., 637 F.3d 1269, 1279 (Fed.Cir.2011). “In order to prove infringement, a patentee must show that every limitation of the claims asserted to be infringed is found in the accused device.” Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562, 1565 (Fed.Cir.1997).

The infringement inquiry has two steps: (1) “the claim must be properly construed to determine its scope and meaning” and (2) “the claim as properly construed must be compared to the accused device or process.” Absolute Software, Inc. v. Stealth Signal, Inc., 659 F.3d 1121, 1129 (Fed.Cir.2011) (quotation marks omitted). The Court’s Claim Construction Opinion and Order of August 23, 2013 represents the first step. The second step — -assessing infringement by way of a comparison — remains. Because the allegedly infringing product in a Hatch-Wax-man Act case is not yet on the commercial market, the infringement inquiry focuses on what is likely to be sold following FDA approval. See Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed.Cir.2002).

“The second step in [this two-step] analysis is to apply the claims to the accused device.” Allen Eng’g Corp. v. Bartell Indus., Inc., 299 F.3d 1336, 1345 (Fed. Cir.2002). The accused device literally infringes a claim “when each of the claim limitations ‘reads on,’ or in other words is found in, the accused device.” Id.

Where the accused product does not literally infringe a claim limitation, the patentee may nonetheless prove infringement under the doctrine of equivalents. See generally Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997). To prove infringement of a claim through the doctrine of equivalents the patentee must prove that the difference between a missing claim element and what is found in the accused product is only “insubstantial.” Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 610, 70 S.Ct. 854, 94 L.Ed. 1097 (1950); TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1376-77 (Fed.Cir.2008). More specifically, the finder of fact inquires “whether a substitute element matches the function, way, and result of the claimed element, or whether the substitute element plays a role substantially different from the claimed element.” Warner-Jenkinson Co., 520 U.S. at 40, 117 S.Ct. 1040. This analysis is known as “the function, way, and result” test.

The doctrine of equivalents has important limits. “There can be no denying that the doctrine of equivalents, when applied broadly, conflicts with the definitional and public-notice functions of the statutory claiming requirement.” Id. at 29, 117 S.Ct. 1040. The Court therefore scrupulously applies the function-way-result test, remaining “specially vigilant against allowing the concept of equivalence to eliminate any claim limitations completely.” Allen Eng’g Corp., 299 F.3d at 1345.

C. The Affirmative Defense of Patent Invalidity

A defendant “in any action involving ... infringement of a patent” may plead as an affirmative defense that the asserted patent is invalid. 35 U.S.C. § 282(b)(2)-(3); see also Microsoft Corp. v. i4i Ltd., — U.S. -, 131 S.Ct. 2238, 2242, 180 L.Ed.2d 131 (2011). Because “[a] patent shall be presumed valid,” “[t]he burden of establishing invalidity ... rest[s] on the party asserting such invalidity.” 35 U.S.C. § 282(a). A defendant asserting patent invalidity must demonstrate invalidity by clear and convincing evidence. Microsoft Corp., 131 S.Ct. at 2242.

1. Novelty and Anticipation

An invention must be novel in order to receive a valid patent. 35 U.S.C. § 102. “Invalidity based on lack of novelty (often called ‘anticipation’) requires that the same invention, including each element and limitation of the claims, was known or used by others before it was invented by the patentee.” Hoover Grp., Inc. v. Custom Metalcraft, Inc., 66 F.3d 299, 302 (Fed.Cir.1995). A patent is therefore invalid due to anticipation when “a single prior art reference ... expressly or inherently disclose[s] each claim limitation.” Finisar Corp. v. DirecTV Group, Inc., 523 F.3d 1323, 1334 (Fed.Cir.2008). The doctrine’s application is encapsulated in the old chestnut: “[t]hat which infringes, if later, would anticipate, if earlier.” Upsher-Smith Labs., Inc. v. Pamlab, LLC, 412 F.3d 1319, 1322 (Fed.Cir.2005) (quoting Peters v. Active Mfg. Co., 129 U.S. 530, 537, 9 S.Ct. 389, 32 L.Ed. 738 (1889) (quotation marks omitted)).

The anticipating reference need not explicitly spell out each element of the anticipated patent claim, but rather can teach a claim limitation if the “teaching is inherent in [the] prior art reference.” Corning Glass Works v. Sumitomo Elec. USA, Inc., 868 F.2d 1251, 1262 (Fed. Cir.1989). To show inherent anticipation, a defendant must demonstrate clearly and convincingly that a claim limitation not disclosed in the anticipating reference will always be present when the prior art is practiced as taught in that reference. Glaxo Inc. v. Novopharm Ltd., 52 F.3d 1043, 1047-48 (Fed.Cir.1995). “Inherent anticipation requires that the missing descriptive material is ‘necessarily present,’ not merely probably or possibly present” in the anticipating reference. Trintec Indus., Inc. v. Top-USA Corp., 295 F.3d 1292, 1295 (Fed.Cir.2002) (quoting In re Robertson, 169 F.3d 743, 745 (Fed.Cir. 1999)).

In considering whether a prior art reference anticipates a claim, courts do not consider whether that reference includes optional elements of the claim. After all, “optional elements do not narrow the claim because they can always be omitted.” In re Johnston, 435 F.3d 1381, 1384 (Fed.Cir.2006). Whether a device includes or excludes the optional element does not determine whether it is an embodiment of the claimed invention, see id., so optional elements do not affect an anticipation analysis. Cf. Upsher-Smith Labs., Inc., 412 F.3d at 1322.

Anticipation and its subsidiary issues are questions of fact. Amkor Tech., Inc. v. Int’l Trade Comm’n, 692 F.3d 1250, 1254 (2012) (anticipation); Telemac Cellular Corp. v. Topp Telecom, Inc., 247 F.3d 1316, 1328 (2001) (inherency).

2. Obviousness and Nonobviousness

“Generally, a party seeking to invalidate a patent as obvious must demonstrate by clear and convincing evidence that a skilled artisan would have been motivated to combine the teaching of the prior art references to achieve the claimed invention, and that the skilled artisan would have had a reasonable expectation of success in doing so.” OSRAM Sylvania, Inc. v. Am. Induction Techs., Inc., 701 F.3d 698, 706-07 (Fed.Cir.2012) (quotation marks omitted). “The Supreme Court has warned, however, that, while an analysis of any teaching, suggestion, or motivation to combine known elements is useful to an obviousness analysis, the overall obviousness inquiry must be expansive and flexible.” Id. at 707 (citing KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 415, 419, 127 S.Ct. 1727, 167 L.Ed.2d 705 (2007)).

A claim must have been nonobvious “at the time the invention was made.” 35 U.S.C. § 103(a). Accordingly, courts must avoid the improper use of hindsight in this analysis and ought not “simply retrace[] the path of the inventor.” See Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358, 1364 (Fed.Cir. 2008). Therefore, unlike in an analysis of novelty, an inherent property of a prior art reference contributes to obviousness only to the extent that the inherent property was known at the time of the invention. See In re Newell, 891 F.2d 899, 901 (Fed. Cir.1989); In re Adams, 53 C.C.P.A. 996, 356 F.2d 998, 1001-02 (1966).

“The ultimate judgment of obviousness is a legal determination.” KSR Int’l Co., 550 U.S. at 427, 127 S.Ct. 1727. That legal determination rests on “underlying factual inquiries including: (1) the scope and content of the prior art, (2) the differences between the claimed invention and the prior art, (3) the level of ordinary skill in the art, and (4) objective indicia of nonobviousness.” Pregis Corp. v. Kappos, 700 F.3d 1348, 1354 (Fed.Cir.2012); see also Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17-18, 86 S.Ct. 684, 15 L.Ed.2d 545 (1966).

The analysis of obviousness must therefore include consideration of secondary, objective indicia. See, e.g., Power Integrations, Inc. v. Fairchild Semiconductor Int’l, Inc., 711 F.3d 1348, 1368 (Fed.Cir.2013). “Objective evidence of nonobviousness can include copying, long felt but unsolved need, failure of others, commercial success, unexpected results created by the claimed invention, unexpected properties of the claimed invention, licenses showing industry respect for the invention, and skepticism of skilled artisans before the invention.” Id. In order for commercial success to provide a secondary indication of nonobviousness, the success of the commercial product must arise from the patent claims at issue. See, e.g., King Pharms., Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1281 (Fed. Cir.2010); Brown & Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 1130 (Fed.Cir.2000) (“A nexus between commercial success and the claimed features is required.”). And in considering whether there was “a long-felt, unmet need” that the invention satisfied — another secondary indication of nonobviousness, see Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324, 1332 (Fed.Cir.2009)— the starting point is “the date of an articulated identified problem and evidence of efforts to solve that problem.” Tex. Instruments v. U.S. Int’l Trade Comm’n, 988 F.2d 1165, 1178 (Fed.Cir.1993).

3. Written Description and Enablement

A patent is invalid if it violates the “written description” or “enablement” clauses of 35 U.S.C. § 112. Section 112 demands both (1) that a patentee adequately disclose his or her invention to the public, and (2) that the patent enable others to replicate it. Id. § 112(a). The written description requirement and the enablement requirement are distinct, and the patent must satisfy both. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1344 (Fed.Cir.2010) (en banc).

a) Written Description

A patent’s “description must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed.” Ariad Pharm., 598 F.3d at 1351. To analyze a patent’s written description, a court considers “whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Id. (quotation marks, alterations, and citations omitted). Thus, a court must conduct “an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art.” Id. The invention that must be adequately described is measured by the asserted claims. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1565 (Fed.Cir.1991). The issue of written description is one of fact. Id.

b) Enablement

A valid patent must disclose enough detail to enable a person of ordinary skill in the art to practice the invention “without undue experimentation at the time of filing.” ALZA Corp. v. Andrx Pharms., LLC, 603 F.3d 935, 939 (Fed.Cir. 2010). “The key word is ‘undue,’ not ‘experimentation.’ ” In re Wands, 858 F.2d 731, 737 (Fed.Cir.1988). Accordingly, patents are not required to be blueprints for commercial production of a product. See CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1339 (Fed.Cir.2003). Furthermore, “a patent need not teach, and preferably omits, what is well known in the art.” Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1365 (Fed.Cir.2006) (quotation marks and alteration omitted).

“Although the ultimate determination of whether one skilled in the art could make and use the claimed invention without undue experimentation is a legal one, it is based on underlying findings of fact.” Transocean Offshore Deepwater Drilling, Inc. v. Maersk Drilling USA, Inc., 699 F.3d 1340, 1355 (Fed.Cir.2012) (quotation marks omitted). Factors to consider include: (1) quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability of the art; and (8) the breadth of the claims. See In re Wands, 858 F.2d at 737. While “a specification need not disclose what is well known in the art,” the requirement of an enabling disclosure is not satisfied by complete reliance on a skilled artisan’s knowledge. Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed.Cir. 1997).

4. Definiteness

A valid patent “particularly point[s] out and distinctly claim[s] the invention.” 35 U.S.C. § 112(b). “Because claims delineate the patentee’s right to exclude, the patent statute requires that the scope of the claims be sufficiently definite to inform the public of the bounds of the protected invention.” Halliburton Energy Svcs., Inc. v. M-I LLC, 514 F.3d 1244, 1249 (Fed.Cir.2008). A patent that does not satisfy this requirement fails to put the public on notice of what would infringe and what would not infringe. See id.; Athletic Alternatives, Inc. v. Prince Mfg., Inc., 73 F.3d 1573, 1581 (Fed.Cir. 1996). Thus, to meet the definiteness requirement a patent must “clearly circumscribe what is foreclosed from future enterprise.” United Carbon Co. v. Binney & Smith Co., 317 U.S. 228, 236, 63 S.Ct. 165, 87 L.Ed. 232 (1942), quoted in Halliburton Energy Svcs., Inc., 514 F.3d at 1249.

The definiteness analysis boils down to whether a claim limitation is “insolubly ambiguous,” such that a court could not construe the claim. See Datamize, LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1347 (Fed.Cir.2005). For example, in Halliburton Energy Services, Inc., a claim limitation requiring that a certain material be a “fragile gel” without further detail was found to be insolubly ambiguous because “neither [the patentee’s] proposed definition nor any other possible construction resolves the ambiguity of the scope of the term.” 514 F.3d at 1250. Other indefinite claims include those that “recite[ ] means-plus-function elements without disclosing corresponding structure in the specification, ... include! ] a numeric limitation without disclosing which of multiple methods of measuring that number should be used, ... and contain! ] a term that is completely dependent on a person’s subjective opinion.” Id. (internal citations and quotation marks omitted)

D. Product-by-Process Claims

A patent claim may describe a product “ ‘at least in part in terms of the method or process by which [the product] is made.’ ” Bonito Boats, Inc. v. Thunder Craft Boats, Inc., 489 U.S. 141, 158 n. *, 109 S.Ct. 971, 103 L.Ed.2d 118 (1989) (quoting 3 Chisum on Patents § 8.05, p. 8-67 (1988)). A patentee can state a claim in product-by-process form by reciting a product and a series of steps by which that product is obtainable. Eg., Abbott Labs, v. Sandoz, Inc., 566 F.3d 1282, 1295 (Fed. Cir.2009). For instance, when “the claimed physical properties of [a product] are attributable to the process that is used to make [it],” the claims are to a product made by a process. Andersen Corp. v. Fiber Composites, LLC, 474 F.3d 1361, 1372 (Fed.Cir.2007). An accused product infringes a product-by-process claim only if it is made by a substantially identical process. See Atl. Thermoplastics Co., Inc. v. Faytex Corp., 970 F.2d 834 (Fed.Cir. 1992).

A court determines the obviousness of a product-by-process claim without reference to its process limitations. Greenliant Sys., Inc. v. Xicor LLC, 692 F.3d 1261, 1268 (Fed.Cir.2012); Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1366-67 (Fed.Cir.2009). The same is true for determinations of novelty or anticipation. See SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1318 (Fed.Cir.2006), reh’g and reh’g en banc denied, 453 F.3d 1346 (Fed.Cir.2006). Conversely, for the purposes of written description and enablement, unlike obviousness and novelty, the Court gives meaning to the process terms of the patent because the specification must describe and enable the full scope of the claims. See 35 U.S.C. § 112; cf. Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed.Cir.1991).

E. Attorneys Fees

In a lawsuit for patent infringement, “[t]he court in exceptional cases may award reasonable attorney fees to the prevailing party.” 35 U.S.C. § 285. The U.S. Court of Appeals for the Federal Circuit has explained Section 285’s limitation to “exceptional cases” in this way:

A case may be deemed exceptional where there has been some material inappropriate conduct related to the matter in litigation, such as willful infringement, fraud or inequitable conduct in procuring the patent, misconduct during litigation, vexatious or unjustified litigation, conduct that violated Fed.R.Civ.P. 11, or like infractions.

Brooks Furniture Mfg., Inc. v. Dutailier Int’l, Inc., 393 F.3d 1378, 1381 (Fed.Cir. 2005) (citing cases). In order for a court to award fees to the prevailing party, that party must demonstrate by clear and convincing evidence that the case is exceptional. See id. at 1384.

PART 2. THE LOW-ABUK PATENTS

I. Findings of Fact

A. Purdue’s development of lowABUK oxycodone

The FDA approved Original OxyContin in 1995. (Stipulations or Agreed Statements of Fact or Law, Joint Pretrial Order, Case No. 04 Md. 1603, Dkt. No. 572, filed Aug. 28, 2013, at 24 [hereinafter 2013 Stip.] ¶ 42.) Purdue brought Original Oxy-Contin to market, heralding its design as a eontrolled-release tablet. {See Gasdia 2012 Tr. 477.) In other words, OxyContin’s significant advantage over other opioid pain relievers was its ability to sustain the release of its API over a twelve-hour period. {See id.; Sellers 2013 Tr. 81-82.) The API in OxyContin is oxycodone hydrochloride (“oxycodone HC1”). (Wuest 2012 Tr. 610.)

In 2000, Rhodes Technologies, then Purdue’s wholly owned subsidiary, began to construct a facility to manufacture oxycodone hydrochloride. (Shamblen 2012 Tr. 76.) Purdue aimed to use the oxycodone API produced by that facility in its Oxy-Contin products. Rhodes synthesized the API in three steps: first, it oxidized thebaine, a derivative of the opium poppy, to form 14-hydroxy; second, Rhodes hydrogenated the 14-hydroxy to form oxycodone free base; and third, it added hydrochloric acid to form oxycodone hydrochloride salt. {Id. at 80; Kupper 2012 Tr. 124-25; PTX 304 at P2378483.)

In February 2003, Purdue submitted a supplemental NDA to the FDA, seeking approval for Rhodes to manufacture its oxycodone API. (Stipulations or Agreed Statements of Fact or Law, Joint Pretrial Order, Case No. 10 Civ. 3734, Dkt. No. 168, filed Oct. 12, 2012, at 14 [hereinafter 2012 Stip.] ¶ 38; PTX 304.) The FDA responded in January 2004, setting forth several conditions for its approval of the drug master file. (PTX 266.) Among those conditions, the FDA directed Rhodes to either provide evidence that the level of 14-hydroxy in its oxycodone API was safe or else lower the level of 14-hydroxy in the API to less than ten parts per million (10 ppm). (Id.)

Purdue proposed that the FDA temporarily allow Rhodes to produce oxycodone API with up to 500 ppm 14-hydroxy, while the company worked toward the 10 ppm limit. (PTX 305 at P2378417-18; Shamblen 2012 Tr. 88-89; Kelly 2012 Tr. 514.) The FDA accepted the proposal. (Kelly 2012 Tr. 514-15; PTX 267.) To achieve the 500 ppm purity level, the Rhodes facility practiced “better washing and better drying” of its product using a high-capacity, high-efficiency spherical dryer and a centrifuge. (Shamblen 2012 Tr. 89-90.) In March 2004, Rhodes submitted an amended drug master file that summarized this intermediate production process. (PTX 268.)

By the fall of 2004, Rhodes had developed a permanent solution to the 14-hy-droxy levels. On November 12, 2004, Rhodes submitted to the FDA a second amendment to its drug master file. (PTX 269; PTX 308; Kelly 2012 Tr. 517-18.) Rhodes described a revised manufacturing process that used a “new low ABUK step” designed to “convert any residual [14-hy-droxy] that reappeared after the normal processing into the final product of oxycodone hydrochloride.” (Shamblen 2012 Tr. 93.) Rhodes reported that this process achieved less than 5 ppm of 14-hydroxy in each of three validation lots. (PTX 269 at P2376224; PTX 308 at P2379581.) The FDA approved Rhodes as a commercial supplier of oxycodone API on March 15, 2005. (PTX 382; Kelly 2012 Tr. 519-20.)

Rhodes had begun experimenting with ways to reduce 14-hydroxy levels in its oxycodone hydrochloride years before the FDA’s 2004 mandate. (See Kupper 2012 Tr. 129-32.) In 2001 and 2002, Rhodes focused on the second synthesis step — the step of hydrogenating 14-hydroxy into oxycodone — for a quick fix. More specifically, Rhodes hypothesized that the unwanted 14-hydroxy in the end product was merely left-over 14-hydroxy that had not been hydrogenated in this second step. So its scientists attempted to control the 14-hy-droxy in the final API by ensuring that “the hydrogenation reaction from [14-hy-droxy] [to] oxycodone free base was run to completion.” (Id. at 129.) Rhodes’s scientists thought they had succeeded: they ran this extended hydrogenation step, analyzed samples of the oxycodone free base using high-performance liquid chromatography (“HPLC”), and found no 14-hy-droxy. (Id. at 133-34; PTX 374). The HPLC analysis had a lower limit of detection of 100 ppm (PTX 374), giving Rhodes great confidence that it had found its answer.

As the Rhodes scientists soon discovered, however, their answer was incomplete at best. When they finished the third and final synthesis step — creating a salt from the oxycodone free base by adding hydrochloric acid — they tested the final API and found that the 14-hydroxy had returned in vast quantities. (Kupper 2012 Tr. ,135, 137-38.) Although there had been no sign of 14-hydroxy in the oxycodone free base after step two, it rebounded to “a level of around 1,500 [ppm]” in the final API of oxycodone hydrochloride after step three. (Id.)

Scratching their heads at the reappearance of 14-hydroxy after the final synthesis step, Rhodes scientists resumed their research into the sources of the 14-hy-droxy and how to remove it. (Id. at 137.) That research program quickly bore fruit. In a November 27, 2002, report, Rhodes research scientist Lonn Rider hypothesized that the 14-hydroxy present in the API formed due to the dehydration of two impurities, 8a, 14-dihydroxy-7,8-dihydro-codeinone (“8a”) and 8(3,14-dihydroxy-7,8-dihydrocodeinone (“8(3”). (Id. at 139-41.)

8(3 and 8|3 are diastereomers of 8,14— dihydroxy-7,8-dihydrocodeinone (“8,14-dihydroxy”). (2012 Stip. ¶ 77.) In other words, 8a and 8(3 are two forms of the same compound, namely 8,14-dihydroxy. 8a and 8(3 “have the same atoms connected to other atoms but they differ in the[ ] three-dimensional arrangement of the atoms.” (Heathcock 2012 Tr. 1144; see also Chapman v. Casner, 315 Fed.Appx. 294, 295-96 (Fed.Cir.2009) (discussing 8,14-dih-ydroxy’s stereoisomers).) That difference in three-dimensional arrangement relates to the orientation of a hydroxyl group. The difference is clear in a molecular diagram. In such a diagram:

Carbons and carbon-carbon bonds that lie close to the average plane of the molecule are represented by simple lines. Groups that are oriented toward the viewer are represented through bonds that use a solid wedge symbol. And groups that are oriented away from the viewer, beneath the molecular plane, are represented by [] hashed wedges.

(Wuest 2012 Tr. 554-55.) An ordinarily skilled chemist can tell 8a from 8(3 by those graphical representations. (See Heathcock 2012 Tr. 1211; Molander 2013 Tr. 2198-2200; cf. Wolf 2012 Tr. 1006-07.)

Rider’s focus on 8,14-dihydroxy flowed intuitively from two known principles: First, as Rhodes and Rider knew, 8,14-dihydroxy formed as a byproduct of the first synthesis step. That step, the oxidation of thebaine to yield 14-hydroxy, also produces “several overoxidation products ... in small amounts,” including 8,14-dihy-droxy. (Kupper 2012 Tr. 140.) Second, as Rhodes and Rider knew, 8,14-dihydroxy could undergo acid-catalyzed dehydration to form 14-hydroxy. (DTX 727; Heath-cock 2012 Tr. 1141-42.) Rhodes suspected that the addition of acid at the salt-formation step was converting the 8,14-dihy-droxy to 14-hydroxy. (Kupper 2012 Tr. 138.)

What Rhodes’s scientists still did not know was whether the reappearance of 14-hydroxy resulted from the dehydration of 8(3, 8a, or some combination of the two. In fact, Rhodes’s scientists were uncertain whether 8a even existed. Rhodes’s scientists were familiar with the 8(3 isomer of 8,14-dihydroxy. They “had a reference standard for it,” and there were “easily detectable amounts” present in Rhodes’s oxycodone product. (Id. at 142.) By comparison, Rhodes knew little about the 8a isomer. Purdue’s scientists had previously noted its potential existence in oxycodone products, but no scientific literature discussed 8a. ,(/d) Purdue and Rhodes investigated. Purdue scientist Frank Cheng conducted mass spectral analysis of the suspected 8a isomer. That analysis returned a molecular weight consistent with the hypothesis that 8a was formed during thebaine oxidation. (Id. at 145; PTX 303.) The suspected 8a compound also had a “fragmentation pattern” from the mass spectrum similar to the 8^ isomer. (Kupper 2012 Tr. 145; PTX 303.) Moreover, the compound’s HPLC chromatogram resembled 8|3’s chromatogram. (Kupper 2012 Tr. 145; PTX 303.) This evidence suggested that the oxidation step produced both 8(3 and 8a.

Knowing that both isomers were present after the second synthesis step (oxidation), Rhodes’s scientists set to work studying which isomer dehydrated to 14-hydroxy in the third synthesis step (salt formation). (See Rider 2012 Tr. 211.) In January 2003, Rider “conducted an experiment to examine the stability of oxycodone hydrochloride solution in isopropanol and water under the conditions” of the Rhodes spherical dryer used in the salt-formation step. (Id.; PTX 312.) Rider sampled the resulting solution. (Rider 2012 Tr. 215.) He discovered that the amount of 14-hydroxy had increased compared to the free base, the amount of 8a had decreased compared to the free base, and the amount of 8p had roughly stayed the same. (Id. at 211, 216-17.) In other words, while 8(3 stayed constant, levels of 8a and 14-hydroxy changed in a complementary manner. To Rider and the other Rhodes scientists, the experiment confirmed that 8a was the “culprit.” (Id. at 217-18; Kupper 2012 Tr. 147-48.) 8a was transforming into 14-hydroxy.

Having discovered 8a as the source of the 14-hydroxy problem, Rhodes scientists set out to solve that problem. Rhodes and Purdue entertained several potential solutions, but the one that stood out immediately was the addition of a further hydrogenation step, at the end of the three-step oxycodone hydrochloride synthesis, to convert the remaining 14-hydroxy into oxycodone. (Rider 2012 Tr. 219-21; Kupper 2012 Tr. 151.) This solution occurred to Dr. Robert Kupper, a Rhodes scientist, immediately: “[o]nee the mechanism of formation was known, the hydrogenation was the first thing that popped into my mind.” (Kupper 2012 Tr. 197.) And besides having support in scientific principles, this solution was productive both because Rhodes “had excess equipment” for the task and because it had “several million dollars worth of oxycodone hydrochloride” in its inventory that would become usable product if the second hydrogenation step succeeded in converting the remaining 14-hydroxy into oxycodone. (Id. at 151.)

This new hydrogenation step did not, however, exactly replicate the hydrogenation of 14-hydroxy in oxycodone free base, as Rhodes had done in its original synthesis steps. That original hydrogenation step used water and formic acid to produce a formate salt, which Rhodes then “converted to the free base by an addition of a base of sodium hydroxide.” (Rider 2012 Tr. 298; see Kupper 2012 Tr. 151-52.) The newly-added hydrogenation step, by contrast, happened after the free base had been converted to oxycodone hydrochloride. (Rider 2012 Tr. 299.) This hydrogenation converted 14-hydroxy into oxycodone but did not react with previously formed oxycodone hydrochloride. (Id. at 300-01.)

By June 2003, Rhodes’s laboratory could routinely produce oxycodone API with 14-hydroxy levels less than 10 ppm using the two-hydrogenation process. (Kupper 2012 Tr. 152; PTX 343 at P2217855.) Method in hand, Rhodes scientists worked to fit the method into the factory manufacturing process. They set up the factory process by July 2004 and submitted the amended drug master file to the FDA in November 2004. (Kupper 2012 Tr. 153.)

B. Purdue obtains the '799, '800, and '072 Patents

Purdue and Rhodes’s work on lowABUK oxycodone yielded three further patents in March 2010: the '799, '800, and '072 Patents. (2012 Stip. ¶ 23.) Broadly speaking, the '800 Patent claims “a process for preparing an oxycodone salt substantially free of 14-[hydroxy].” (E.g., PTX 3 at 34:21-22.) The'072 Patent claims low-ABUK “oxycodone hydrochloride active pharmaceutical ingredient.” (E.g., PTX 4 at 34:56-59.) The '799 Patent claims an “oral dosage form” of lowABUK oxycodone hydrochloride. (E.g., PTX 2 at 34:54-64.)

Purdue’s patents did not come easily. They required years of advocacy before the U.S. Patent and Trademark Office (“PTO”), the Board of Patent Appeals and Interferences, and the U.S. Court of Appeals for the Federal Circuit. Because the parties dispute the significance of the history of the patents, the Court highlights aspects of that history here.

1. The Chapman Application

The '799, '800, and '072 Patents continue from application No. 11/391,897, known as the “Chapman Application.” (See 2013 Stip. ¶ 27(a)-(c).) The Chapman Application, in turn, continues from the March 30, 2005 application No. 11/093,626, which issued as U.S. Patent No. 7,129,248. (See id.) As with the patents-in-suit, the Chapman Application recited a “process for preparing oxycodone hydrochloride having less than 25 ppm [14-hydroxy].” Purdue was the real party in interest behind the Chapman Application. (DTX 715; Bjorge 2012 Tr. 1048-49,1070.)

On April 19, 2007, the Board of Patent Appeals and Interferences declared an interference between the Chapman Application and U.S. Patent No. 7,153,966 (known as “Casner”). (2012 Stip. ¶ 26.) That action, Patent Interference 105,553, concerned a claim from the Chapman Application and one from the Casner patent. (DTX 715.)

The relevant claims, claim 1 of the Casner patent and claim 96 of the Chapman Application, “relatefd] to a method for making oxycodone using a hydrogenation step” for the purpose of “the formation of oxycodone having low levels” of ABUKs. (Id. at P1057606; Bjorge 2012 Tr. 1052.) Chapman’s claim 96 disclosed a process for making oxycodone similar to claim 1 of the '800 Patent, but without any limitation that a portion of the 14-hydroxy must have derived from the 8a isomer. (PTX 10 at P1056017.) The Board further stated that Chapman claims 96-118 “correspond” to the subject matter of the interference. (DTX 715 at P1057605.) Chapman claims 115-118 called for “the process according to claim 96, wherein the resultant oxycodone contains [14 — hydroxy] in an amount less than” various purity limits ranging from 25 ppm to 5 ppm. (DTX 678 at P1055888.)

Casner, the junior party in the interference, asked the Board to rule that the Chapman Application was invalid as obvious. (DTX 715 at P1057640; Bjorge 2012 Tr. 1070.) On March 13, 2008, the Board declared the subject matter of the interference to be obvious. (See 2012 Stip. ¶ 31.) The Board characterized the purported invention as “a method for making oxycodone using a hydrogenation step” for the purpose of forming “oxycodone having low levels ... of [ABUK] impurities.” (DTX 715 at P1057606.) The Board compared Chapman’s claims to the prior art and concluded that “the principal difference[ ]” between them was that “no one reference describes all of the claimed process steps.” (Id. at P1057625.) The Board concluded that “[b]ased on the record before us, we hold that the subject matter of Chapman claim 96 and ... Casner claim 1 would have been obvious within the meaning of 35 U.S.C. § 103.” (Id. at P1057640.)

Purdue appealed directly to the Federal Circuit. See Chapman, 315 Fed.Appx. at 294. The Federal Circuit agreed with the Board and affirmed the Board’s conclusion that claim 96 of the Chapman Application was obvious and therefore unpatentable. See id. at 297-98. The Federal Circuit reasoned that “claim 96 would have been obvious if properly-combinable references disclosed conditions suitable to promote reaction of 8,14-dihydroxy to 14-hydroxy. The prior art references here do just that: they indicate that [8p], at least, will under certain reaction conditions form 14-hy-droxy.” Id. at 297.

2. Further proceedings before the PTO

Purdue filed several continuations of the Chapman Application. The '799 Patent continued as Serial No. 11/653,531 and issued on March 9, 2010. The '800 Patent continued as Serial No. 11/729,741 and issued on March 9, 2010. The '072 Patent continued as Serial No. 11/653,529 and issued on March 23, 2010. (2012 Stip. ¶ 23.)

The PTO initially rejected as obvious a number of asserted claims of the patents as they were then drafted. The Examiner paid particular attention to one prior art reference, U.S. Patent No. 6,177,567 (the “Chiu” patent), which disclosed a process for preparing a low-ABUK oxycodone crude base. (PTX 10 at P1052803-04; PTX 11 at P1034148-49; PTX 12 at P1045523-24; PTX 741.) The Examiner observed:

Chiu teaches that in order to determine the completeness of the reaction, the disappearance of [14-hydroxy] was determined by HPLC ... and further teaches that if the reaction was discerned to be incomplete, the batch was stirred for an additional 2h period. Therefore, it would have been obvious to one skilled in the art to prepare the instant Oxycodone hydrochloride composition having less impurities with different levels of [14-hydroxy] since Chiu teaches determining levels of [14-hy-droxy] by HPLC during preparation of Oxycodone or its salt.

(PTX 12 at P1045524.)

The Examiner also questioned the non-obviousness of the patents on the grounds that prior art regarding 80 might render obvious those claims relating to 8a. As the Examiner wrote, “unless applicants provide some unexpected results of [8a] as compared to [80], it would have been obvious to one skilled in the art to prepare Oxycodone salt with reduced amount of 14-hydroxy[ ] with reasonable expectation of success.” (PTX 11 at P1035381-82; Heathcock 2012 Tr. 1142^3.)

Purdue’s response distinguished the pri- or art based on stereochemistry (the spatial arrangement of atoms) and based on the process steps involved in the Chiu reference. As to the stereochemistry, Purdue submitted the declaration of Dr. Steven Baldwin to demonstrate the “unexpected results” of 8a to the Patent Office. Baldwin stated that 8a and 80 are “different compounds and have surprisingly different properties (e.g. reactivities).” (PTX 11 at P1035678; Heathcock 2012 Tr. 1143.) As to the Chiu reference, Purdue explained that the prior art reference concerned 14-hydroxy in oxycodone free base, not 14-hydroxy that “would reappear during hydrochloride salt formation.” (PTX 10 at P1052961-62; see Crimmins 2012 Tr. 799-800.)

Purdue prevailed. The Examiner approved the patents, in part “due to [Purdue’s] persuasive arguments and declaration by Dr. Baldwin.” (PTX 10 at P1059552.)

3. The low-ABUK patents-in-suit

Purdue has asserted that Teva’s ANDA infringes claims 3 and 19 of the '799 Patent; claims 30-34 and 76-79 of the '800 Patent; and claims 1, 4, and 5 of the '072 Patent. The '799, '800, and '072 Patents have substantially identical specifications but differ in the nature of the claims.

Each of the three patents has an identical “Figure 1,” which depicts the synthesis of oxycodone hydrochloride from thebaine. First, thebaine undergoes oxidization, yielding 14-hydroxy. Second, the 14-hy-droxy is hydrogenated to produce oxycodone free base. Third, a hydrochloride solution acidifies that oxycodone free base, resulting in oxycodone hydrochloride. In addition, another reaction appears alongside the first synthesis step: over-oxidation of the thebaine, forming 8a. In depicting this reaction, Figure 1 identifies 8a both by name and by graphical representation. (PTX 2 at 6; PTX 3 at 6; PTX 4 at 6; Wuest 2012 Tr. 554-55,1253-54.)

Figure 2, identical in each of the three low-ABUK patents, provides further context regarding 8a. It depicts the conversion of 8a into 14-hydroxy as a result of dehydration in the presence of acid. (PTX 2 at 7; PTX 3 at 7; PTX 4 at 7; Wuest 2012 Tr. 1254.) Here, as in Figure 1, the 8a isomer is labeled as such and is further identified by graphical representation. Even the caption of Figure 2 recites the isomer’s name, for a belt-and-suspenders identification: “Dehydration of 8a,14-hihy-droxy-7,8,-dihydrocodeinone.” (PTX 2 at sheet 2, fig. 2.)

By way of a taxonomy of the isomers, the patents’ specifications all state that “[t]he term 8,14-dihydroxy-7,8-dihydroco-deinone includes either 8a,14-dihydroxy-7,8-dihydrocodeinone; or 8(3,14 — dihydroxy — 7,8 — dihydrocodeinone or can include a mixture of both compounds.” (E.g., PTX 3 at 5:54-57.)

The common specification includes no method for detecting 8a. (Kupper 2012 Tr. 191; Wuest 2012 Tr. 1324-25.) However, the description goes on to recite the chemical structure of 8a and the nature of the reaction that produces it. For example, the specification states that 8,14-dihy-droxy converts to 14-hydroxy “during salt formation reactions known in the art.” (PTX 3 at 8:4-11.) The patents’ written description does not explicitly identify conditions that transform 8a, but not 8(3, into 14-hydroxy. (See, e.g., Rider 2012 Tr. 278.) The specification also does not disclose a pH range at which 8a will not form. (Id. at 278-79; Wuest 2012 Tr. 1330-31.) But Example 3 of the specification demonstrates conditions that suffice to convert 8a into 14-hydroxy. (Wuest 2012 Tr. 1258.) Furthermore, as Dr. James Wuest explained at trial, a skilled artisan “would understand that the 8(3 compound is essentially inert under [the] conditions [of Example 3] and would not undergo this acid-induced transformation.” (Id. at 1258.)

The reactivity or inertness of 8(3 under the conditions of Example 3 represent a fulcrum in the arguments over how much the common specification discloses about 8a. After all, in arguing that an ordinary skilled artisan would understand the patents’ reference to 8a, Purdue relies on the premise that the patent’s reader understands Example 3 as not referring to 8(3. Example 3 uses hot 0.2N hydrochloride, with 0.2N representing the normality, or the equivalent concentration of the acid. (Id. at 1258-59.) In that acid, according to Example 3, the 8,14-dihydroxy reacts, decreasing from 0.29% to 0.04%. (PTX 3 at 26:8-11.) Wuest credibly opines that an ordinary skilled artisan would know that the 8,14-dihydroxy reacting in those conditions must be 8a and not 8(3, because the Weiss reference shows that 8(3 is inert in such conditions. (Wuest 2012 Tr. 1258; Wuest 2013 Tr. 2364-65; see Ulrich Weiss, Derivatives of Morphine II Demethylation of 14-Hydroxycodeinone 14-Hydroxymorphinone and 8,14-Dihydroxydihydromor-phinone, 22J. Org. Chem. 1505-078 (1957) (“Weiss”) (DTX 727).) As Wuest explains, Weiss shows 8(3 reacting in 6N hydrochloride (“HC1”) and not reacting in 2N HC1. (Wuest 2013 Tr. 2305-06.) An ordinarily skilled chemist would understand that 6N HC1 is more concentrated than 2N HC1, which in turn is more concentrated than 0.2N HC1, and that an acid-catalyzed reaction that occurs in 6N HC1 but not in 2N HC1 will not occur in 0.2N HC1. (See Wuest 2012 Tr. 1255-61,1287-90; Heath-cock 2012 Tr. 1187-90; Wuest 2013 Tr. 2303-13.)

Teva has attempted to show just the opposite, that 8(3 reacts and is not inert under the conditions of Example 3. They put forth Dr. Brian Smith’s experimental results that replicate Weiss’s work to show the reactivity of 8 (3 in 6N HC1 (Smith 2013 Tr. 2044-47) and that attempt to extrapolate through limited testing how 8(3 behaves in 2N HC1 (id. at 2037-52). The Court cannot credit this extrapolation as reliable evidence of reactivity: Smith did not measure the purity of the 8p base at the start of his experiment in 2N HC1 (in contrast to his experiment in 6N HC1, which began with a measurement of the 8(3 base’s purity), thereby eliminating any substantial meaning from the purity he measured at the end of his experiment. (See id. at 2047; Wuest 2013 Tr. 2307-09.) Moreover, even assuming arguendo that Smith’s 2N HC1 experiment began with the purity of 8(3 base that Teva assumes, the large extent of the reaction into 14-hydroxy could not be explained by 8|3 alone; at least some 8a must have contributed to the reaction. (See Wuest 2013 Tr. 2311-13, 2441-42.) On balance, Wuest’s credible explanation of the Weiss reference, balanced against Teva’s attacks on that explanation, persuades the Court that a person of ordinary skill in the art would have read Example 3 as describing 8a.

C. The Noramco process

Teva proposes to use oxycodone API manufactured by Noramco, Inc. (2013 Stip. ¶ 110.) Noramco is an FDA-approved supplier of oxycodone API. (Kelly 2012 Tr. 510-11.) At trial, the parties intensely disputed whether 8a forms during Noramco’s manufacturing process and, if it does, whether some of that 8a converts to 14-hydroxy during the final salt formation st