# Pfizer Inc. v. Teva Pharmaceuticals USA, Inc.

> District Court, D. New Jersey · March 20, 2007 · 482 F. Supp. 2d 390

URL: https://www.frixlaw.com/law-library/cases/2310522

## Case

- **Full name:** PFIZER INC., Pharmacia Corp., Pharmacia & Upjohn Inc., Pharmacia & Upjohn Company, G.D. Searle & Co., G.D. Searle LLC, Searle LLC (Delaware) and Searle LLC (Nevada) Plaintiffs, v. TEVA PHARMACEUTICALS USA, INC. Defendant
- **Court:** District Court, D. New Jersey
- **Decided:** March 20, 2007
- **Citations:** 482 F. Supp. 2d 390; 2007 U.S. Dist. LEXIS 20190; 2007 WL 1146472
- **Precedential status:** Published
- **Opinion:** Opinion by Lifland
- **Judges:** Lifland
- **Cited by:** 6 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/2310522

## Opinion text

FINDINGS OF FACT AND CONCLUSIONS OF LAW
LIFLAND, District Judge.
Plaintiffs, Pfizer, Inc., Pharmacia Corp., Pharmacia & Upjohn Inc., Pharmacia
&
Upjohn Company, G.D. Searle & Co., G.D. Searle LLC, Searle LLC (Delaware), and Searle LLC (Nevada) (collectively “Pfizer” or “Plaintiffs”) allege infringement of U.S. Patent Nos. 5,466,823 (the “ ’823 Patent”); 5,563,165 (the “ ’165 Patent”); and 5,760,-068 (the “ ’068 Patent”) (collectively the “patents-in-suit”) by Teva Pharmaceuticals U.S.A., Inc. (“Teva” or “Defendant”). The patents-in-suit are directed toward eele-eoxib, the active ingredient in Celebrex, and a broad genus of compounds that in-
*395
eludes celecoxib, pharmaceutical compositions including such compounds, and methods of using such compounds.
For the reasons set forth below,
1
the Court finds that Teva has failed to prove obviousness, inequitable conduct, a violation of the best mode requirement, or obvious-type double patenting by clear and convincing evidence. Thus, the patents are neither invalid nor unenforceable, and Teva has infringed the patents under 35 U.S.C. § 271 (e)(2).
BACKGROUND
I. A Brief History of Anti-Inflammatory Drugs
The precise biological reason people suffer from pain and inflammation is not yet fully understood. However, great progress has been made in recent decades toward understanding and treating the pain and other symptoms associated with inflammatory conditions. Around the turn of the century, researchers at Friedrich Bayer & Co. invented aspirin, which quickly gained popularity as a painkiller. Over the next several decades similar drugs— classified as traditional non-steroidal anti-inflammatory drugs (“NSAIDs”) — were introduced into the market, including ibuprofen and naproxen. Yet it was not until the early 1970s that the mechanism of action of these drugs was understood. In simplified terms, scientists eventually discerned that traditional NSAIDs worked by blocking the production of prostaglandins in cells. Prostaglandins are small molecules that are associated with both pain and inflammation, and with “good housekeeping” functions, such as contributing to good gastrointestinal physiology and blood clotting. These prostaglandin molecules are produced in the body when arachidonic acid (a fat found in cell membranes) is catalyzed by cyclooxygenase (COX) enzymes. Traditional NSAIDs inhibited the COX enzyme, thus preventing the creation of prostaglandins and the associated pain and inflammation.
[[Image here]]
This discovery also shed light on the cause of some of the reported side effects of traditional NSAIDs. It had been known for some time that NSAIDs were associated with gastrointestinal (“GI”) side effects, ranging from discomfort to serious life threatening ulcers, yet the cause of these GI risks was unclear. With the dis
*396
covery of the prostaglandin pathway, it became clear that in addition to reducing the negative effects of prostaglandins, traditional NSAIDs like aspirin also reduced the positive “housekeeping” functions, thus causing potentially severe GI risks. This new knowledge was an important step in the ongoing effort to invent a new kind of NSAID that would treat pain and inflammation without causing GI side effects.
The next breakthrough in anti-inflammatory drug development came in the 1970s and 1980s when scientists established that there were in fact two different kinds of COX enzymes: one responsible for producing good housekeeping prosta-glandins (COX-1), and one responsible for producing prostaglandins associated with pain and inflammation (COX-2). (See figure below.)
[[Image here]]
COX-1 was fully identified and sequenced in 1988. COX-2 was sequenced in 1991. Once both enzymes were sequenced, scientists hypothesized that it might be possible to selectively inhibit COX-2, thus creating a GI sparing NSAID. However, due to the similarity of the two enzymes, there was significant skepticism as to whether it would be possible to develop a drug that selectively inhibited either enzyme.
Scientists became more hopeful in 1992 after Dr. William Galbraith of DuPont-Merck gave a presentation at a prostaglan-din conference in Keystone, Colorado (“the Keystone Conference”). Dr. Galbraith’s presentation focused on a compound called DuP 697, which he reported might be a COX-2 selective inhibitor. Following the Keystone Conference, pharmaceutical companies stepped up their efforts to create a COX-2 selective compound, and thus began what Teva has characterized as a “race” to develop the first COX-2 selective inhibitor, with Pfizer and Merck as the two frontrunners.
II. Celebrex and the Patents-in-Suit
For Pfizer, the finish line of the COX-2 selective inhibitor race was Celebrex. Sometime between August and November 1993,
2
Pfizer scientists invented several
*397
new compounds they believed would selectively inhibit the COX-2 enzyme. One of the compounds was celecoxib.
On November 30, 1993, Pfizer filed U.S. Application No. 08/160,594 (the “ ’594 Application”), covering a broad range of chemical compounds, as well as pharmaceutical compositions utilizing the compounds, and methods of treatment. On July 12, 1994, the Patent Examiner issued a restriction requirement requiring Pfizer to select either the compound claims, the composition claims, or the method claims to prosecute, and further required Pfizer to elect a single species within the chosen group for examination.
Pfizer elected to prosecute the compound claims and chose the species described in example # lc (celecoxib) as the elected species. The Examiner then defined a “generic concept inclusive of the elected species ... for examination along with the elected species.” The ’594 Application, as narrowed, was approved and ultimately issued as the ’823 Patent. Pfizer filed several divisional applications covering the compounds that were not embraced by the ’823 Patent. These patents were issued, but are not relevant here. Pfizer also filed a divisional application covering compositions. This divisional application issued as the ’165 Patent. Finally, Pfizer also filed international application PCT12720 covering methods. This application entered the national stage as the T13 Application, and ultimately issued as the ’068 Patent. (See figure below.)
[[Image here]]
After the patents-in-suit were issued, Pfizer scientists conducted further testing of the compounds covered by the patents to identify a compound to develop into a commercial drug. Several compounds that initially seemed to be promising candidates were discarded after further testing revealed unacceptable properties such as excessive half-life or liver toxicity. Eventually, scientists selected celecoxib as the preferred compound and, following clinical trials, submitted a New Drug Application to the Food and Drug Administration (“FDA”) for Celebrex. The FDA ap
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proved Celebrex as a COX-2 selective NSAID for the treatment of osteoarthritis and rheumatoid arthritis on December 31, 1998. Celebrex was launched the following year, and almost immediately achieved enormous and sustained success in the marketplace.
III. Teva’s Abbreviated New Drug Application
The Hatch-Waxman Amendments to the Federal Food, Drug, and Cosmetic Act permit an applicant to file an Abbreviated New Drug Application (“ANDA”) with the Food and Drug Administration (“FDA”) requesting approval of a bioequivalent (“generic”) version of a drug that is already listed by the FDA as approved for safety and effectiveness without having to submit additional safety and efficacy data.
See
21 U.S.C. § 366 (j)(2)(A). An ANDA may be filed for drugs currently protected by patents. In its filing, the applicant must certify either (1) that it will not market its drug prior to the expiration of the relevant patents, or (2) that the relevant patents “are invalid or will not be infringed by the manufacture, use or sale of the new drug for which the ANDA is submitted.” 21 U.S.C. § 355 (j)(2)(A)(vii)(IV). An ANDA applicant filing its application with the FDA and making a Section TV certification must notify the holder of the patent, who may then bring an action against the applicant for infringement under 35 U.S.C. § 271 (e)(2).
See
21 U.S.C. §§ 355 (j)(2)(B)(i) and (j)(6)(B)(iii); see
also, e.g., SmithKline Beecham Corp. v. Apotex Corp.,
439 F.3d 1312, 1314 (Fed. Cir.2006). Submission of an ANDA is an act of patent infringement if the ANDA seeks approval to manufacture, use, or sell a drug that is claimed in a patent or the use of which is claimed in a patent. 35 U.S.C. § 271 (e).
Teva filed Abbreviated New Drug Application No. 76-898 with the FDA. The application was addressed to a proposed drug March 19, 2007 product identified as “Ce-leeoxib Capsules, 100 mg, 200 mg, and 400 mg.” The ANDA contained a Section IV certification challenging the validity of the patents covering celecoxib.
IV. The Current Litigation
In February 2004, Pfizer filed an action against Teva for infringement. In May 2004, Teva filed an answer and asserted an affirmative defense claiming that the patents-in-suit are invalid or unenforceable due to obviousness under 35 U.S.C. § 103 (a), inequitable conduct, and violation of the best mode requirement, and that the ’068 Patent (covering methods of use) is invalid for obvious-type double patenting over the T65 Patent (covering pharmaceutical compositions).
The parties tried the case before the Court from November 13 through December 8, 2006 and on December 13, 2006. Written closing statements were submitted to the Court on February 1, 2007.
JURISDICTION, VENUE AND APPLICABLE LAW
This Court has subject matter jurisdiction over Pfizer’s patent infringement claims pursuant to 28 U.S.C. §§ 1331 and 1338(a). Venue is proper under 28 U.S.C. §§ 1391 and 1400(b).
Because this action arises under the patent laws of the United States, this Court must apply the precedents of the United States Court of Appeals for the Federal Circuit, which has jurisdiction over any appeal of this judgment.
See
28 U.S.C. § 1295 (a).
STANDARD OF REVIEW
Patents enjoy a presumption of validity. 35 U.S.C. § 282 (“A patent shall be presumed valid.”). The party challenging the patent bears the burden of proving by clear and convincing evidence the inval
*399
idity or unenforceability of the claims of a patent.
See id; see also Alza Corp. v. Mylan Labs., Inc.,
464 F.3d 1286, 1289 (Fed.Cir.2006). “The ‘clear and convincing’ standard of proof of facts is an intermediate standard which lies somewhere between ‘beyond a reasonable doubt’ and a ‘preponderance of the evidence,’ ” and “has been described as evidence which produces in the mind of the trier of fact an abiding conviction that the truth of [the] factual contentions [is] ‘highly probable.’ ”
Buildex, Inc. v. Kason Indus., Inc.,
849 F.2d 1461, 1468 (Fed.Cir.1988) (internal quotation omitted). Thus, Teva bears the burden of proving each of its defenses of patent invalidity/unenforceability, and each element of those defenses, by clear and convincing evidence.
ANALYSIS
I. OBVIOUSNESS
Pursuant to § 103 of the United States Code, a patent is invalid if the claimed invention was “obvious” at the time it was created. The test for obviousness is “whether the claim at issue would have been obvious to one of ordinary skill in the art at the time of the patent.”
Avia Group Int'l, Inc. v. L.A. Gear California, Inc.,
853 F.2d 1557, 1563 (Fed.Cir.1988);
see also Alza Corp. v. Mylan Labs., Inc.,
464 F.3d 1286, 1289 (Fed.Cir.2006) (“[A] claimed invention is unpatentable if the differences between it and the prior art are ‘such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art.’ ”) (quoting 35 U.S.C. § 103 (a)). In adjudicating obviousness, four factors — called the
Graham
factors — must be considered: “(1) the scope and content of the prior art; (2) the level of ordinary skill in the prior art; (3) the differences between the claimed invention and the prior art; and (4) objective evidence of nonobviousness.”
In re Dembiczak,
175 F.3d 994, 998 (Fed.Cir.1999) (citing
Graham v. John Deere Co.,
383 U.S. 1, 17-18 , 86 S.Ct. 684 , 15 L.Ed.2d 545 (1966)).
“For a chemical compound, a
pri-ma facie
case of obviousness requires ‘structural similarity between claimed and prior art subject matter ...
where the prior art gives reason or motivation to make the claimed compositions.’
”
Yamanouchi Pharm. Co. v. Danbury Pharmacol, Inc.,
231 F.3d 1339, 1343 (Fed.Cir. 2000) (emphasis added) (quoting
In re Dillon,
919 F.2d 688, 692 (Fed.Cir.1990) (en banc)). Accordingly, this Court must apply the “motivation-suggestion-teaching” test, which asks “whether a person of ordinary skill in the art, possessed with the understandings and knowledge reflected in the prior art, and motivated by the general problem facing the inventor, would have been led to make the combination recited in the claims.”
In re Kahn,
441 F.3d 977 , 988 (Fed.Cir.2006). In other words, a
pri-ma facie
case of obviousness requires the party to “explain the reasons one of ordinary skill in the art would have been motivated to select the references and to combine them to render the claimed invention obvious.”
Id.
at 986 (internal quotations omitted). Evidence of motivation to combine need not be found explicitly in the prior art — it “may be implicit from the prior art as a whole,”
In re Kotzab,
217 F.3d 1365, 1370 (Fed.Cir.2000), or evident from the general knowledge of a person of ordinary skill,
Alza Corp. v. Mylan Labs., Inc.,
464 F.3d 1286, 1291 (Fed.Cir.2006);
In re Kahn,
441 F.3d 977 , 988 (Fed.Cir. 2006).
3
*400
Importantly, “[bjecause 35 U.S.C. § 103 (a) orders a Court to determine whether the subject matter was obvious ‘at the time the invention was made,’ the obviousness inquiry cannot be performed using hindsight.”
Janssen Pharmaceutica N.V. v. Mylan Pharms., Inc.,
456 F.Supp.2d 644, 654-55 (D.N.J.2006);
see also Orthopedic Equipment Co., Inc. v. United States,
702 F.2d 1005, 1012 (Fed.Cir.1983) (“It is wrong to use the patent in suit as a guide through the maze of prior art references, combining the right references in the right way so as to achieve the result of the claims in suit. Monday morning quarterbacking is quite improper when resolving the question of nonobviousness in a court of law.”). The motivation-suggestion-teaching test “stands as a critical safeguard against hindsight analysis and rote application of the legal test for obviousness.”
In re Rouffet,
149 F.3d 1350, 1358 (Fed.Cir.1998).
Teva contends that celecoxib and other compounds within the genus of the ’823 Patent would have been obvious to a person of ordinary skill in the art in November of 1993. In brief, Teva’s theory of obviousness is that the person of ordinary skill would have derived a pharmacophore from the disclosure of the Merck T96 Application's Patent,
4
and then used the pharmacophore, his/her general knowledge of pharmaceutical chemistry, and the teachings of two other references— the T42 Patent and the Fujisawa ’829 Application — to create twelve obvious compounds, including celecoxib.
As an initial matter, the Court finds that the ’196 Application/’995 Patent is not pri- or art to the patents-in-suit because the Merck ’995 Patent is not entitled to claim priority to the filing date of the T96 Application. This finding alone warrants a ruling for Pfizer since Teva’s entire theory of obviousness hinges on this reference. However, even assuming
arguendo
that the ’196 Application/’995 Patent is prior art, the Court finds that Teva has failed to meet its burden of proving a
prima facie
case of obviousness. As explained in detail below, Teva has not shown that the person of ordinary skill would derive the proposed pharmacophore or that the pharmacophore would inexorably lead to the creation of celecoxib as one of the twelve allegedly obvious compounds.
Accordingly, the Court finds that the patents-in-suit are not invalid for obviousness.
A.
The Date of Invention
At the outset, the Court must determine the precise invention date for cele-coxib. Because the Court must evaluate obviousness “at the time the invention was made,” the invention date is a threshold question that will guide the entire obviousness analysis. “A general rule in patent law is that the date of invention ... is presumed to be the date [the applicant] files a complete patent application in the Patent and Trademark Office disclosing the invention.” 1
Chisum on Patents
§ 3.08. This presumption can be overcome
*401
by proof of either: (1) an earlier reduction to practice of the invention, or (2) an earlier conception of the invention coupled with due diligence from the date of conception to a subsequent reduction to practice or to the filing of the application.
Id.; Dow Chemical Co. v. Halliburton Co.,
631 F.Supp. 666, 704 (N.D.Miss.1985),
aff’d
790 F.2d 93 (Fed.Cir.1986). “[This earlier] date, if established, is the ‘time the invention was made’ used in determining obviousness under 35 U.S.C. § 103 .”
Dow Chemical,
631 F.Supp. at 704 (N.D.Miss. 1985) (citing
Lockheed Aircraft Corp. v. United States,
213 Ct.Cl. 395 , 553 F.2d 69, 74 (1977)).
Here, the invention date has been an issue of considerable dispute. The filing date for the application was November 30, 1993. However, shortly before the trial began, Pfizer asserted an earlier invention date of August 2, 1993 on the ground of earlier conception of the invention coupled with due diligence from the date of conception to a subsequent reduction to practice or to the filing of the application
(i.e.,
ground (2) above). Specifically, Pfizer asserted that “it conceived the invention claimed in the patents-in-suit at least as early as August 2, 1993 and worked with reasonable diligence continuously through the time it filed for patent protection.” (Decl. of Michael Patunas in Support of Teva’s in Limine Motion No. 1, Ex. G at ¶ 9;
see also
Opinion on Teva’s Motion in Limine No. 1.)
5
To support its assertion of an August 2, 1993 conception date, Pfizer relied upon pages from the laboratory notebook of Dr. Bertenshaw, one of the inventors of cele-coxib. The notebook pages, dated August 2, 1993, disclosed a broad genus of chemical compounds with several substituents in several positions. Celecoxib was within the genus
(i.e.,
one could derive celecoxib by picking certain groups out of the possibilities listed in notebook pages), but the notebook pages provided no direction to celecoxib — no instruction or even suggestion to select these groups out of the plethora of possibilities provided.
Pfizer initially sought this earlier invention date in order to antedate the Fujisa-wa ’829 Application (with a publication date of August 11, 1993), which Teva originally indicated was an important piece of its obviousness theory. At trial, however, the parties’ respective positions began to shift. Teva did not rely heavily on the ’829 Application. Pfizer meanwhile questioned the appropriateness of starting with the ’196 Application/’995 Patent by introducing other patents — with effective dates later than August 2, 1993 — that the person of ordinary skill could have started with instead. These patents would not have been available to the person of ordinary skill if the date of invention was set at August 2, 1993, as Pfizer initially argued it should be. On the second day of trial, Teva’s counsel “concede[d] the invention date is at least in October,” but did not elaborate further. (Trial Trans. II 30:6.) The trial concluded without further elaboration from either party as to the invention date they respectively believed should be accepted by the Court.
Teva elaborated for the first time in its response to a Rule 52 motion filed by
*402
Pfizer at the close of Teva’s case-in-chief. In its response papers Teva argued that the proper invention date was October 4, 1993, since Pfizer scientists first synthesized celecoxib
(i.e.,
reduced it to practice) no later than that date. An October 4, 1993 invention date would benefit Teva’s obviousness argument in two ways. First, it would make the ’829 Application viable prior art to the patents-in-suit.
See infra
Section I.B.2. Second, as discussed in Section I.D.l(c), Pfizer proffers several possible starting points for the development of new NSAIDs that it contends would have been more appealing to the person of ordinary skill than the one Teva relies on. Two of these proposed starting points are patents that resulted from applications which were filed in November 1993. These patents would not have been available to the person of ordinary skill on October 4,1993.
Since the invention date had been a “moving target” throughout the trial and pre-trial proceedings, the Court sent a letter to counsel requesting that Pfizer “include a clear explication of [its] position regarding the proper invention date in its reply papers.” Letter to Counsel re:
Pfizer v. Teva,
Civ. Action No. 04-754 (Dec. 26, 2006). Pfizer did address the invention date in its reply papers — and moved the target once again. Pfizer abandoned its August 2 invention date argument, and urged the Court to adopt November 30, 1993 (the filing date of the patents-in-suit) as the default invention date.
Accordingly, there are three potential invention dates on the table. As noted, Pfizer no longer asserts an invention date of August 2, 1993. Nor does the Court find there to be adequate support for conception of the invention on that date.
6
This leaves October 4, 1993, and November 30, 1993, as the possible invention dates. As per the general rule,
see supra,
the Court will use November 30, 1993, as the default invention date unless there is clear and convincing evidence of the earlier October 4th date. The Court finds that there is.
This case presents a unique situation. Generally, it is the patent holder who seeks to assert an earlier invention date in order to antedate a prior art reference or to establish priority in the context of an interference. Here, however, it is
*403
Teva that asserts the earlier invention date of October 4,1993, based on Pfizer’s reduction to practice on or before that date. In support of its assertion, Teva cites several pieces of evidence, including Pfizer’s own statement in an interrogatory response that Pfizer scientists synthesized celecoxib at least as early as October 4,1993:
Interrogatory No. 28
Identify when, where and how the compound [celecoxib], and any pharmaceuti-cally acceptable salts thereof, were first synthesized, the individual(s) that conducted such synthesis, the individual(s) that directed such synthesis, and any analysis of the results of such synthesis.
Response to Interrogatory No. 28
Plaintiffs object to the term “any analysis of the results of such synthesis” as vague and ambiguous. Subject to the general and specific objections,
plaintiffs respond that celecoxib was first synthesized at least as early as October I, 1998
by Julie M. Miyashiro at G.D. Searle & Co.’s facilities in Skokie, Illinois.
(Declaration of Michael E. Patunas in Support of Teva’s Post-Trial Brief, Exh. 3, at 3 (emphasis added).) In the typical scenario, there are concerns over the credibility of the patent holder’s own self-serving testimony regarding an earlier date of conception or reduction to practice.
Chen v. Bouchard,
347 F.3d 1299, 1309 (Fed.Cir. 2003);
Mahurkar v. C.R. Bard, Inc.,
79 F.3d 1572, 1577 (Fed.Cir.1996). However, those concerns are inapplicable in the current situation where the earlier invention date hurts, rather than helps, the patent holder. Accordingly, the Court will give due weight to Pfizer’s own
self-defeating
statements regarding an earlier reduction to practice.
Furthermore, Pfizer’s statement is not the only evidence in the record that supports the October 4th date. There is documentary and testimonial evidence that corroborates the reduction to practice of celecoxib on this date. A page from the laboratory notebook of inventor Julie Mi-yashiro describes the synthesis (reduction to practice) of celecoxib. The page is dated October 4, 1993, and was signed and witnessed in accordance with Pfizer’s “Guidelines for Research Records.”
See
DTX 53;
see also
Deposition of Julie Marion Miyashiro Vol. 1 (Nov. 3, 2005), at 109:21-112:12. Accordingly, there is ample evidence to support the October 4th reduction to practice date, and the Court finds October 4, 1993 to be the correct invention date
for the individual compound celecoxib.
The next issue, therefore, is whether the synthesis of one species, celecoxib, supports an invention date of October 4, 1993, for all of the asserted claims of the ’823 Patent. The Court finds that it does. One of the asserted claims of the ’823 Patent (claim 9) covers only celecoxib.
7
Synthesis of celecoxib on October 4 certainly supports an October 4, 1993 invention date for this claim. The remaining asserted claims cover genuses of compounds that include celecoxib. The Court finds that the synthesis of celecoxib — an individual species within those genuses— on October 4, 1993 is sufficient to establish that date as the proper invention date for the genus claims as well.
The Board of Patent Appeals has held that the first party to conceive a species is the first to conceive of the generic invention.
Miller v. Walker,
214 U.S.P.Q. 845 , 847, 1982 WL 50432 (Bd.Pat.App.1982). Although the Federal Circuit has not made
*404
such a definitive statement, it has held that “conception of a species within a genus
may
constitute conception of the genus.”
8
Oka v. Youssefyeh,
849 F.2d 581, 584 (Fed. Cir.1988) (emphasis added);
see also In re Jolley,
308 F.3d 1317 , 1322 n. 2 (Fed.Cir. 2002). Moreover, the predecessor to the Federal Circuit has held that a prior reduction to practice of a species establishes priority to the genus in the context of an interference and “precludes another party from claiming that he is the first inventor of the genus containing the species.”
Mikus v. Wachtel,
504 F.2d 1150, 1151 (C.C.P.A.1974). Based on this caselaw, the Court finds that the date on which an individual species within a genus is reduced to practice constitutes the invention date for genus claims that include the species.
In re Zletz,
cited by Pfizer, is not to the contrary. In
Zletz,
the Federal Circuit stated: “Priority to a genus may indeed be shown by prior invention of a single species, but the genus will not be patentable to an applicant unless he has generic support therefor.”
In re Zletz,
893 F.2d 319, 323 (Fed.Cir.1989) (internal citation omitted). The first clause of this quotation simply restates the rule explained above and adopted by this Court that invention of a species can establish invention of a genus containing that species. The second clause of the sentence — contrary to Pfizer’s interpretation — does not negate this sentiment. The import of the second clause is that even though a party can establish
priority
to a genus by showing earlier invention of an individual species, he will not ultimately be able to
obtain a patent
for the genus unless he can provide adequate § 112 support therefor.
See id.
(citing
In re Grimme,
47 C.C.P.A. 785 , 274 F.2d 949, 952 (1960) (discussing the disclosure required to support a generic claim in the field of chemistry)).
Accordingly, the Court finds the invention date for celecoxib and the asserted claims of the ’823 Patent to be October 4, 1993.
9
B.
The Scope and Content of the Pri- or Art
“The scope and content of the prior art is limited to art that is analogous to the claimed invention. Analogous art is that which is from the same field of endeavor or, if not within the field of endeavor, is still reasonably pertinent to the particular problem with which the inventor is involved.”
Janssen Pharmaceutica N.V. v. Mylan Pharms., Inc.,
456 F.Supp.2d 644, 652 (D.N.J.2006).
As
explained above, Teva argues that the patents-in-suit are obvious in light of three prior art references: the Merck T96 Application/’995 Patent, the Fujisawa ’142 Patent, and the Fujisawa ’829 Application. Pfizer disputes that the ’196 Application and the ’829 Application are prior art to the patents-in-suit. The prior art status of these two references is discussed below.
1. The Merck ’196 Application/’995 Patent Is Not Prior Art
On June 24, 1993, Merck and Co., Inc. (“Merck”) filed U.S. Patent Application 08/082,196 (the “ ’196 Application”) entitled “Phenyl Heterocycles as COX-2 Inhibitors.” In early November 1993, Merck withdrew several claims of the ’196 Appli
*405
cation from consideration. On November 23, 1993, the Patent Examiner rejected the remaining claims under 35 U.S.C. § 112 for failing to adequately teach how to use the claimed invention for failure to satisfy the enablement requirement). The Examiner explained:
the claims are directed to compounds which selectively inhibit COX-2, compositions containing them, and methods of treating cyclooxegenase mediated diseases using said compounds. The discovery of COX-2 is a recent development in the art, as indicated in the instant specification, and relatively little is known about it and its properties.... Relatively little is known regarding the activity of COX-2, and there is no predictability as to which compounds will inhibit COX-2. In such a field, the data found in the specification regarding the activity of the claimed compounds is not sufficient to enable the full scope of the invention as claimed. Even within the limited set of compounds tested for activity, the variation of activity is so great that the data cannot be said to create the expectation that the multitude of compounds claimed will have the claimed activity.
(PTX 34 at PFC 02019556.)
On January 10, 1994, Merck filed a continuation-in-part (“CIP”) application Serial No. 08/179,467 (the “’467 Application”). The ’467 Application included substantial additional data, including
in vivo
data. Shortly thereafter, on February 22, 1994, Merck expressly abandoned the 196 Application. In the remarks section of the express abandonment, Merck stated as follows:
In an informal interview [the patent examiner] clarified that with regard to the compounds and their use as anti-inflammatory agents, she is concerned that there is insufficient proof that inhibition of COX-2 would translate into anti-inflammatory activity.
In response, applicants point out that this is a question [of] utility (35 USC 101) rather than a failure to teach how to use under 35 USC 112. Indeed, applicants have extensively taught “how to use.” See for Example pages 10-16 of the specification. In that there is no 101 rejection, Applicants must assume that the Examiner is not concerned about utility. Accordingly, the present rejection is traversed.
In any event, the above mentioned CIP renders the Examiner’s concern moot, in that rat paw edema assay data are provided demonstrating that applicants!’] compounds are useful anti-inflammatory agents.
(Id.
at PFC 02019560-61.) On December 12, 1995, CIP Application ’467 issued as U.S. Patent No. 5,474,995 (the “ ’995 Patent”).
A patent is available as prior art as of the actual filing date of the application that resulted in the patent.
See In re Wertheim,
646 F.2d 527, 534 (C.C.P.A.1981). The reasoning underlying this rule is that the patent could have issued on that day but for delays in the patent office, and “[a]s Justice Holmes said in
Milbum,
‘The delays in the patent office ought not to cut down the effect of what has been done.’ ”
Id.
A question arises where, as here, the patent issues from a CIP application: Is the patent considered prior art as of the date the original parent application was filed (here, June 24,1993), or only as of the filing date of the CIP (here, January 10, 1994)? This distinction is critical here because the CIP was filed after the invention date for the claims at issue in this case.
10
*406
As such, the ’995 Patent can only be prior art if it is entitled to claim priority to the June 24, 1993 filing date of its original ’196 Application.
The Federal Circuit has addressed this question, and has held that a patent issuing from a CIP is entitled to the earlier filing date of its parent application if — and only if — the disclosures of the parent provide adequate § 112 support for the claims that actually appear in the patent as issued.
11
See, e.g., Go Med. Indus. Pty., Ltd. v. Inmed Corp.,
471 F.3d 1264 , 1270 (Fed.Cir.2006) (“A patent application for an invention disclosed in a previously-filed application in a manner that satisfies all the requirements of 35 U.S.C. § 112 is entitled to the benefit of the earlier filing date.”);
see also In re Wertheim,
646 F.2d at 538 (holding that entitlement to an “earlier U.S. filing date for the patent necessarily depends on further compliance with §§ 120 and 112”).
12
Accordingly, determining whether a patent is entitled to claim priority to its parent’s filing date generally requires the Court to examine both the parent application and the resulting patent and independently evaluate whether the patent claims were fully supported by the disclosures of the parent application; as applied to this case, the question is whether the disclosures of the ’196 Application provide adequate §112 support for the claims of the ’995 Patent.
Entitlement to claim priority to the filing date of a parent application may not be available under certain circumstances.
See Pennwalt Corp. v. Akzona Inc.,
740 F.2d 1573, 1579 (Fed.Cir.1984). In
Penn-walt,
the plaintiffs subsidiary filed a patent application that was rejected by the Patent and Trademark Office (“PTO”) under 35 U.S.C. § 112 for failure to satisfy the enablement requirement.
Id.
at 1579 . Following this rejection, the subsidiary abandoned the original application and filed a CIP application describing the claims in more detail.
Id.
The Federal Circuit held that (1) the filing of a CIP in response to a § 112 rejection creates a rebuttable presumption of acquiescence in the PTO’s determination that the original application did not comply with the requirements of § 112, and (2) that a finding of acquiescence precludes an inventor from claiming entitlement to the filing date of the original application.
Id.
at 1579-80. The reason for this preclusion is simple: An inventor who acquiesced in the PTO’s conclusion that the claims did not meet the statutory requirements for patentability is estopped from later claiming that these requirements were in fact met.
See, e.g.,
4
Chisum on Patents
§ 11.03.
The
Pennwalt
Court thus made clear that a finding of acquiescence is a threshold finding, which eliminates the need to independently evaluate whether the claims of an issued patent are supported by the disclosure of a rejected application.
Id.
at 1580 n. 13;
see also Moll v. Northern Telecom. Inc.,
No. 94-5451, 1995 WL 676420 , at *3, 1995 U.S. Dist. LEXIS
*407
17053, at *10 (E.D.Pa. Nov. 5, 1995) (explaining that a finding that the inventor acquiesced in the PTO’s final rejection of the earlier parent application “eliminates the need to [independently evaluate] whether the claims of the patent that issued were supported by the disclosure of the rejected application.”).
Notably,
Pennwalt
and other cases that apply the acquiescence rule generally involve a different factual situation from the instant case. Typically, a patent holder seeks the benefit of the parent application’s earlier filing date in order to antedate a potentially invalidating reference.
See, e.g., Max Daetwyler Corp. v. Input Graphics, Inc.,
608 F.Supp. 1549 (E.D.Pa. 1985). Here, by contrast, an alleged in-fringer is seeking the benefit of a parent application’s earlier filing date in order to make a third party’s patent available as a prior art reference to the patents-in-suit.
Pfizer urges the Court to apply the
Pennwalt
framework here, and argues that the Court need not independently evaluate whether the claims of the ’995 Patent are fully supported by the disclosures of the ’196 Application because “[t]he ‘filing of a CIP application to overcome a PTO rejection’ gives rise to a rebuttable ‘presumption of acquiescence in the rejection,’ resulting in a presumption that the applicant is not entitled to the earlier filing date.” (Pfizer’s Post-Trial Brief at 8 (citing
Pennwalt,
740 F.2d at 1578 ).) Teva disagrees, arguing that the
Pennwalt
framework is not applicable in this factual situation.
The Court finds that the first step of the
Pennwalt
framework is applicable here, but not the second. The Court agrees with Teva that the estoppel reasoning underlying step two does not apply where, as here, the party arguing for the earlier filing date is not the party that allegedly acquiesced in the PTO rejection. In other words, Teva should not be es-topped from arguing that the § 112 requirements were satisfied with respect to the relevant claims of the Merck ’196 Application just because Merck (an entirely unrelated party) acquiesced in the PTO’s conclusion that the claims did not meet those requirements.
Cf. Arkla, Inc. v. U.S.,
37 F.3d 621, 624 (Fed.Cir.1994) (explaining that the parties must have had a full and fair opportunity to litigate the subject at issue for estoppel to apply);
Bd. of Trs. of Trucking Employees of North Jersey Welfare Fund, Inc. v. Centra,
983 F.2d 495, 505 (3d Cir.1992) (same).
There is no similar reason to ignore the first step of the
Pennwalt
framework. The idea that the filing of a CIP in response to a § 112 rejection creates a re-buttable presumption of acquiescence in the PTO’s determination that the original application did not comply with the requirements of § 112 is equally applicable in the factual context presented here. And although an ultimate finding of acquiescence would not have a step-two preclu-sive effect in this context, the Court finds that it would still be relevant as evidence that the rejected application did not fully support the claims of the issued patent.
In sum, the Court will apply the following framework to answer the question of whether the ’995 Patent is entitled to claim priority to the filing date of the T96 Application: The Court will evaluate the prosecution history of the ’196 Application to determine whether there is a
prima facie
case of acquiescence, and if so, whether it is rebutted. Regardless of the Court’s finding on this issue, Teva will not be precluded from arguing that the disclosure of the T96 Application provides adequate § 112 support for the claims of the ’995 Patent. The Court will undertake an inde
*408
pendent evaluation of this question, but will consider a finding of acquiescence as part of its analysis.
(a) Merck Acquiesced in the PTO’s Rejection of the ’196 Application
There is
prima facie
evidence that Merck acquiesced in the PTO’s rejection of the ’196 Application based on the fact that Merck filed a CIP (with additional data) in response to the PTO’s § 112 rejection of the Application on enablement grounds.
See supra.
Teva argues that the elements of a
prima facie
case of acquiescence cannot be established because Merck never faced a “final rejection” during prosecution of the Merck ’196 Application.
13
The Court is not persuaded by this argument.
Mr. Ronald Smith, Teva’s expert on patent office practice and procedure, defined a “final rejection” as a rejection made in a “second office action, after the examiner had already rejected the claims, at least once, and an applicant has had a chance to respond to the rejection. If the examiner still feels the rejection is appropriate he would make the second action final.” (Trial Trans. XII 19:13-18.) Mr. Smith also stated that the November 23, 1993 rejection by the patent examiner was not a “final rejection.” (Trial Trans. XII 19:19-21.) Teva points to Federal Circuit caselaw stating that “[e]stoppel does not occur ... in the absence of an explicit
final rejection
under 35 U.S.C. § 112 , first paragraph.”
Waldemar Link, GmbH & Co. v. Osteonics Corp.,
32 F.3d 556, 560 (Fed.Cir.1994).
The Court agrees that the November 23, 1993 rejection of the ’196 Application was not a “final rejection,” but finds that fact to be irrelevant to determining the existence of a
prima facie
case of acquiescence. Teva mis-uses the relevant case-law. Certainly there are cases stating that only a final rejection will give rise to a presumption of acquiescence.
See, e.g., Paperless Accounting, Inc. v. Bay Area Rapid Transit System,
804 F.2d 659, 662-64 (Fed.Cir.1986);
Waldemar,
32 F.3d at 560 . But in both
Paperless Accounting
and
Waldemar
a preliminary § 112 rejection was later withdrawn by the patent examiner in subsequent rejections. “In both cases, the patentee filed the CIP application after the PTO had withdrawn the § 112 objections. Thus, in both cases, there was no acquiescence in a § 112 rejection because there was no pending § 112 rejection when the continuation-in-part application was filed.”
B & S Plastics, Inc. v. Hydro Air Indus., Inc.,
No. SA CV 95-492, 1995 WL 811901 , 1995 U.S. Dist. LEXIS 20791 , at *8-*9 (C.D.Cal. Oct. 10, 1995).
14
Without a pending § 112 rejection at the time the CIP was filed, the applicants were not faced with the choice to fight or submit — and it is the decision to
*409
submit rather than fight that gives rise to the
prima facie
case of acquiescence.
In the present case, by contrast, there was an unambiguous rejection of the ’196 Application under § 112. Merck could have chosen to fight the rejection or submit to it. As Mr. Smith conceded, Merck could have responded to the rejection and asked the patent examiner to reconsider. It did not do so. It filed a CIP that addressed the examiner’s concerns. It chose to submit, impliedly conceding that the disclosure of the application was insufficient. Thus, the elements of a
prima facie
case can be established despite the fact that the rejection was not technically “final.”
Moreover, Teva has offered no alternative explanation for Merck’s decision to file a CIP. In fact, Mr. Smith, Teva’s own witness, conceded that Merck abandoned the T96 Application in favor of the CIP
in response to
the examiner’s rejection:
Q: Then what did the applicants do
in response to the rejection? ...
A: Applicants abandoned the application in favor of the co-pending continuation in part application filed January 10, 1994.
15
(Trial Trans. XI 66:25-67:8 (emphasis added).)
Accordingly, the Court finds that there is
prima facie
evidence of acquiescence, and will turn to the question of whether there is “countervailing evidence” of non-acquiescence.
Pennwalt,
740 F.2d at 1579 . Teva vigorously argues that there is ample countervailing evidence in the prosecution history of the ’196 Application to rebut a finding of acquiescence. Teva points specifically to Merck’s response to the Examiner’s rejection, in which Merck stated that it disagreed with the decision and traversed the rejection.
“Traverse” is a term of art in the patent office. It means that the applicant disagrees with the position of the examiner and requests reconsideration. (Trial Trans. X 157:6-13; see afeo XI 67:22-68:3 (“[Traverse] means that they disagree with the rejection and request that it be withdrawn.”).) Mr. Smith testified that “if an applicant was acquiescing in a rejection, he wouldn’t file a traversal.” (Trial Trans. XII 20:22-23.)
The Court does not find traversal — in the circumstances presented here — to be compelling evidence of non-acquiescence. There are two reasons for this finding: one substantive and one procedural. As to the substance of the traversal, Merck never actually disputed the idea that the data was insufficient to establish the utility of the claimed compounds. It merely argued (erroneously) that this was not a § 112 problem. (PTX 34 at PFC 02019560-61 (“[AJpplicants point out that this is a question [of] utility (35 USC 101) rather than a failure to teach how to use under 35 USC 112. Indeed, applicants have extensively taught ‘how to use.’ In that there is no 101 rejection, Applicants must assume that the Examiner is not concerned about utility. Accordingly, the present rejection is traversed.”).) Thus, the traversal does not illustrate
disagreement
— i.e., non-acquiescence — with the fundamental finding that the disclosed data was insufficient. Moreover, Merck’s argument was legally inaccurate. As discussed further
infra,
it is well
*410
established that the “use” element of the enablement requirement incorporates the utility requirement of 35 U.S.C. § 101 .
See infra; see also, e.g., In re Fisher,
421 F.3d 1365, 1378 (Fed.Cir.2005).
The procedural consideration involves the context of the traversal. Merck traversed
in an express abandonment.
As Mr. Smith explained, because Merck set forth its traversal and accompanying argument in an express abandonment, the PTO was never going to consider or act on the traversal in any way:
Q: [The traversal] is in a document where they [Merck] are expressly abandoning the application, right?
A: Yes.
Q: So they are not going to get the examiner to remove or change the rejection at the time that they are abandoning, right?
A: At the time — no, not at the time.
Q: ... After you file an express abandonment, the Patent Office doesn’t have to do anything in that application other than [mark] it as abandoned, right?
A: I think they send out a letter acknowledging the express abandonment, then send the case the abandoned files.
(Trial Trans. XII 29:22-30:9.) This was not Merck’s only option. The company could have chosen to simply traverse the rejection
without
abandoning the application. Since the rejection was not final, the examiner could have withdrawn or amended the rejection. By traversing in an express abandonment, Merck effectively eliminated this possibility.
For both of these reasons, the Court is not persuaded that Merck’s traversal rebuts the
prima facie
evidence of acquiescence. Accordingly, the Court finds that Merck acquiesced in the PTO’s § 112 rejection of the T96 Application.
As explained above, the inquiry does not end here. ■ The Court must still conduct an independent evaluation of whether the claims of the ’995 Patent are fully supported by the disclosure of the ’196 Application. If so, then all disclosures of the ’196 Application that were carried forward into the ’995 Patent will properly be considered prior art.
See In re Lund,
54 C.C.P.A. 1361 , 376 F.2d 982 (1966). If not, then the ’196 Application/’995 Patent is not prior art, and Teva’s entire theory of obviousness will be effectively eviscerated. Merck’s acquiescence is but one factor that the Court will consider when conducting this analysis.
(b) Claim 6 of the ’995 Patent is Not Supported By the Disclosure of the ’196 Application
Teva contends that claim 6 of the ’995 Patent is fully supported by the disclosure of the T96 Application. The Court disagrees. The parties do not dispute the relevant facts, only the legal conclusions to be derived therefrom.
i.
Undisputed Facts
Claim 6 of the ’995 Patent is a genus claim covering dozens of chemical compounds:
*?
[[Image here]]
The claim requires a furanone core,
16
one phenyl ring with a sulfonamide or methylsulfone substituent, and another phenyl ring with one or two substituents chosen from hydrogen (H), flouro (F), chloro (Cl), or bromo (Br) in any of the available positions. Finally, claim 6 requires that the two phenyl rings be attached at a double bond.
The T96 Application covers several thousand compounds. Tables 1 and 2 of the T96 Application include several examples of covered compounds. (DTX 302 at 31-43.) Examples # 9 and # 10 in table 1 of the T96 Application are within the genus disclosed in claim 6 of ’995 Patent.
(Id.
at 33.) Three (unnumbered) examples in table 2 of the ’196 Application are also within the genus disclosed in claim 6 of ’995 Patent.
(Id.
at 39.) Thus, five— and only five — compounds within the genus of claim 6 of the ’995 Patent are disclosed in the T96 Application. These five compounds are reproduced below:
[[Image here]]
These five compounds show diphenyl fura-nones with one phenyl substituted with a sulfonamide or methylsulfone and with a flourine or chlorine on the second phenyl. Importantly, however, the compounds do not cover the full scope of claim 6. (Trial Trans. VII 126:13-20.) For example, none of the five compounds use a bromine
*412
substituent. None of them include two different substituents. Nor do they cover the full range of possible positions for the mono- or di-substituted substituents.
As for data, the 196 Application includes in vitro data for two of the examples (examples 9 and 10).
(Id.
at 45^6.) There is no in vivo data disclosed in the 196 Application, but it does include a description, written in the past tense, of a rat paw edema assay.
17
(Id.
at 44.)
Finally, the 196 Application provides a detailed description for synthesizing example 9, and a general method for synthesizing example 10. Notably, the synthesis procedure for example 9 set forth in the 196 application is not included in the CIP application or the ’995 Patent. It was replaced by a different procedure.
ii.
The Disclosure of the T96 Application Does Not Satisfy the Written Description Requirement for Claim 6 of the ’995 Patent
A patent must contain a written description of the claimed invention.
See
35 U.S.C. § 112 (stating that the “specification shall contain a written description of the invention”). The written description must reasonably convey to a person of ordinary skill that the inventor possessed the entire invention — here, the entire genus covered by claim 6 of the ’995 Patent — as of the application filing date.
Eiselstein v. Frank,
52 F.3d 1035, 1039 (Fed. Cir.1995);
see also In re Reiffin,
199 Fed. Appx. 965, 967 (Fed.Cir.2006) (not prece-dential) (The “disclosure as originally filed must convey with reasonable clarity to those skilled in the art that [another] was in possession of the invention.”) (internal quotations omitted). Thus, the question in this case is whether the five examples disclosed in the T96 Application would convey to a person of ordinary skill that Merck possessed the entire genus of claim 6 of the ’995 Patent as of the filing date of the ’196 Application.
It is well established that the written description requirement does not require a description of every possible embodiment falling within the scope of a genus claim, and that disclosure of a few species can reasonably convey possession of a genus and thus satisfy the written description requirement.
See, e.g., In re Curtis,
354 F.3d 1347 (Fed.Cir.2004);
Bilstad v. Wakalopulos,
386 F.3d 1116, 1124 (Fed.Cir.2004). Indeed, “disclosure of [even a single] species
may be
sufficient written description support for a later claimed genus including that species.”
Bilstad,
386 F.3d at 1124 . But it is not always sufficient. “There are ... exceptions to the general rule that disclosure of a species provides sufficient written description support for a later filed claim directed to the genus.”
Id.
at 1125 . In
Bilstad ,
the Federal Circuit surveyed several cases that considered the issue of written description support for an added genus claim when only a species was disclosed. The Court determined that the critical distinction between cases where disclosure of a species sufficed and those where it did not was the level of predictability in the relevant art:
The distinction in these cases is based upon what would be reasonably conveyed to a person skilled in the art at the time of the original disclosure. If the difference between members of the group is such that the person skilled in the art would not readily discern that other members of the genus would per
*413
form similarly to the disclosed members, i.e., if the art is unpredictable, then the disclosure of more species is necessary to adequately show possession of the entire genus.
Id.
In other words, the primary exception to the general rule that disclosure of a species is a sufficient written description of a later claimed genus involves inventions in unpredictable fields.
Id.
(“[UJnpredict-ability in the particular field may warrant closer scrutiny of whether disclosure of a species is sufficient to describe a genus.”). In an unpredictable field, a broader disclosure is required.
Pharmaceutical chemistry is a highly unpredictable field.
See, e.g., 2 Chisum, on Patents
§ 5.04 (“Because of the unpredictable nature of chemical reactions, a newly-synthesized compound may be very similar in structure to known and existing compounds and yet exhibit very different properties.”). Indeed, the Federal Circuit has expressly stated that the particular chemistry involved in the development of celecoxib was and is highly unpredictable. In an opinion in separate case involving the development of celecoxib, the Federal Circuit wrote:
Even with the three-dimensional structures of enzymes such as COX-1 and COX-2 in hand, it may even now not be within the ordinary skill in the art to predict what compounds might bind to and inhibit them, let alone have been within the purview of one of ordinary skill in the art in the 1993-1995 period
Univ. Of Rochester v. G.D. Searle & Co., Inc.,
358 F.3d 916, 925 (Fed.Cir.2004). Moreover, the evidence presented in this case confirms the unpredictability of the field. For example, Dr. Talley — one of the inventors of celecoxib — testified about two compounds that were produced by his team. The two compounds were identical except that the positions of two substituent groups were reversed. With the groups in one position, the compound was a good inhibitor. With the groups in the reverse position, the compound was devoid of activity. (Trial Trans. XV 57:15-58:8;
see also id.
at XII 71:18-80:23 (Dr. Seibert);
infra
Section I.D.4.)
In its Post-Trial Brief, Teva contends Dr. Trummlitz testified that based on the disclosure of the 196 Application, the person of ordinary skill would have understood that the inventors of the 196 Application possessed all of the compounds of Claim 6 of the ’995 Patent. (Teva’s Post-Trial Brief at 130.) Teva cites volume four of the trial transcript at 92:17-94:2 and 103:19-114:2. The Court has reviewed the transcript and does not find any such assertion in Dr. Trummlitz’s testimony. Moreover, even if such a statement could be extrapolated from Dr. Trummlitz’s testimony, Teva has offered no persuasive reasoning or supporting evidence as to why or how disclosure of five examples would reasonably convey to a person of ordinary skill that Merck actually possessed the entire genus of claim 6 on June 24,1993.
Teva also argues that three additional compounds that were disclosed on page 41 of the ’196 Application provide written description support for claim 6 of the ’995 Patent. The Court disagrees. The three compounds at issue are 4,5 diphenyl fura-nones. In other words, they are diphenyl furanones with a double bond between the carbon atoms in the 4 and 5 positions. Teva admits that these compounds are not within the scope of claim 6, but nevertheless argues that they should be considered because they are “in equilibrium” with three 3,4 furanones that are within the scope of the claim.
When compounds are in equilibrium, it means that if one compound is present, both will be present. Thus, according to
*414
Teva, when looking at the 4,5 furanones in the ’196 Application, the person of ordinary skill would “immediately envision the 3,4 furanones” as well. (Teva’s Post-Trial Brief at 132.) By way of evidence in support of this assertion, Teva cites to the testimony of Pfizer’s medicinal chemistry expert, Dr. William Jorgensen. Teva asserts that Dr. Jorgensen admitted the different compounds could be in equilibrium, but the Court does not read Dr. Jorgen-sen’s testimony to support this assertion. The relevant testimony was as follows:
Q: That furanone, the 4, 5 configured furanone, would be in equilibrium with a 3, 4 furanone, wouldn’t it?
A: I am not sure you want to go there. For compounds like this you can imagine multiple equilibrium.... They are [in] [equilibrium in the sense that any two isomers, if you have enough heat, it will convert it. That is a better way to do it. If you think about 3, 4, and the 4,5[ ] fura-none, they are different molecules .... And there is some barrier in between them. If there is enough heat you might be able to get them over that barrier or they might decompose on you. So in principal ... now, quote, they are in equilibrium in the sense that they are isomers. And maybe you could equilibriate thermally. Maybe not. Maybe they would decompose.
(Trial Trans. XVI 111:24-112:15.) Dr. Jorgensen clearly stated that the 4,5 fura-nones and the 3,4 furanones are “different molecules,” and that although “they are isomers,” they might “decompose” if one tries to equilibrate them.
(Id.)
Teva offers no evidence other than Dr. Jorgensen’s testimony that the compounds are in equilibrium. Teva’s expert’s did not address the idea. There are no documents that support it. Moreover, Teva offered no evidence, other than its bald assertion, to support the idea that the person of ordinary skill would immediately envision the 3,4 furanones even if the compounds were in equilibrium. Accordingly, the Court will not consider the 4,5 furanones as providing support for claim 6 of the ’995 Patent.
In sum, given the unpredictability of the art, the Court finds that the written description requirement for claim 6 of the ’995 Patent is not satisfied by the disclosure of five individual compounds in the ’196 Application. This finding alone would be sufficient to hold that claim 6 is not fully supported by the disclosure of the ’196 Application; however, the Court also finds that other § 112 requirements are not met.
iii.
The Disclosure of the ’196 Application Does Not Satisfy the Enablement Requirement for Claim 6 of the ’995 Patent
Section 112 also includes an enablement requirement.
See
35 U.S.C. § 112 (“[T]he specification shall contain a written description ... of the manner and process of making and using [the invention] in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same.”). Although related, the written description and enablement requirements are distinct and must be analyzed separately.
See, e.g.,
3
Chisum on Patents
§ 7.04;
Invitrogen Corp. v. Clontech Labs. Inc.,
429 F.3d 1052 , 1071 n. 17 (stating that the “written description requirement is distinct from the enablement requirement”). Even assuming
arguendo
that the disclosure of the ’196 Application satisfies the written description requirement with respect to claim 6 of the ’995 Patent, the claim would not be fully supported because the enablement requirement is not met.
*415
To satisfy the enablement requirement, the disclosure “must teach those skilled in the art how to
make
and
use
the full scope of the claimed invention without ‘undue experimentation.”’
Univ. of Rochester v. G.D. Searle & Co., Inc.,
249 F.Supp.2d 216, 231 (W.D.N.Y.2003). The Federal Circuit has explained the “undue experimentation” standard as follows:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the invention claimed.
PPG Indus., Inc. v. Guardian Indus. Corp.,
75 F.3d 1558, 1564 (Fed.Cir.1996) (quotation and citation omitted). The Federal Circuit has also set forth factors to consider in determining whether a disclosure would require undue experimentation: “(1) the 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 or unpredictability of the art, and (8) the breadth of the claims.”
In re Wands,
858 F.2d 731, 737 (Fed.Cir. 1988).
Importantly, the “use” element of the enablement requirement also incorporates the utility requirement of 35 U.S.C. § 101 :
The how to use prong of
section 112
incorporates as a matter of law the requirement of 35 U.S.C. § 101 that the specification disclose as a matter of fact a practical utility for the invention. If the application fails as a matter of fact to satisfy 35 U.S.C. § 101 , then the application also fails as a matter of law to enable one of ordinary skill in the art to use the invention under 35 U.S.C. § 112 .
In re Ziegler,
992 F.2d 1197, 1200-01 (Fed. Cir.1993) (citations omitted);
see also In re Fisher,
421 F.3d 1365, 1378 (Fed.Cir.2005) (“It is well established that the enablement requirement of § 112 incorporates the utility requirement of § 101.”). In other words, a showing of practical utility of the claimed invention is necessary to satisfy the enablement requirement.
As best as the Court can tell, Teva’s argument is essentially as follows: (1) the synthesis information and in vitro data included in the ’196 Application are sufficient to enable a person of ordinary skill to make and use the five examples disclosed in the ’196 Application, and (2) this is sufficient to enable a person of ordinary skill to make and use all of the compounds covered by claim 6 of the ’995 Patent without undue experimentation.
Turning to the first step of Teva’s argument, Teva asserts that the synthesis information included in the T96 Application would enable a person of ordinary skill to make the disclosed examples, and that the in vitro data disclosed in table 3 of the ’196 Application would be sufficient to prove the utility of the examples, and enable the person of ordinary skill to use them. Pfizer contends that the “use” element of the requirement is not satisfied because, due to the large number of compounds disclosed in the T96 Application and the lack of any in vivo data, there was no basis to conclude that any particular compound of the Application was in fact anti-inflammatory as asserted in the specification.
In vitro data can be sufficient to establish the utility of a chemical compound. In vivo data is not always required.
See, e.g., In re Fisher,
421 F.3d at 1376-78 ;
Cross v. Iizuka,
753 F.2d 1040 (Fed.Cir.1985). In
Cross ,
Iizuka filed an application claiming thromboxane synthe-
*416
tase inhibitors, which were alleged to be useful in treating inflammation, asthma, hypertension, and other health problems. Cross filed an application claiming the same compounds two months later, and the PTO declared an interference. The dispositive issue in the case was whether Iizuka’s application, which included in vi-tro, but not in vivo, data, was sufficient to comply with the practical utility requirement of § 101.
Id.
at 1050. The Board of Patent Appeals held that it was, and the Federal Circuit agreed.
Id.
(“Based upon the facts of this case, we are not persuaded that the Board erred in finding that the
in vitro
utility disclosed in the [Iizuka application] is sufficient to establish a practical utility.”). The Court explained its reasoning as follows:
Opinions of our predecessor court have recognized the fact that pharmacological testing of animals is a screening procedure for testing new drugs for practical utility. This in vivo testing is but an intermediate link in a screening chain which may eventually lead to the use of the drug as a therapeutic agent in humans. We perceive no insurmountable difficulty, under appropriate circumstances, in finding that the first link in the screening chain, in vitro testing, may establish a practical utility for the compound in question. Successful in vitro testing will marshal resources and direct the expenditure of effort to further in vivo testing of the most potent compounds, thereby providing an immediate benefit to the public, analogous to the benefit provided by the showing of an in vivo utility.
Today, under the circumstances of the instant case, where the Japanese priority application discloses an in vitro utility,
ie.,
the inhibition of thromboxane synthetase in human or bovine platelet microsomes, and where the disclosed in vitro utility is supplemented by the similar in vitro and in vivo pharmacological activity of structurally similar compounds,
ie.,
the parent imidazole and 1-methylimidazole compounds, we agree with the Board that this in vitro utility is sufficient to comply with the practical utility requirement of § 101.
Id.
at 1051 (internal citations omitted).
The Court understands the opinion in
Cross
to stand for the proposition that in vitro data can suffice to establish practical utility when “the disclosed in vitro utility is supplemented by the similar in vitro and in vivo pharmacological activity of structurally similar compounds.” In these circumstances, the person of ordinary skill can be reasonably confident that the disclosed compounds will work as claimed despite the lack of in vivo data for the specific compounds covered by the claim. Teva argues that these circumstances are present here because there was published in vitro and in vivo data for the type of compounds claimed in the ’196 Application, substituted diphenyl heterocycles, which would lead the person of ordinary skill to assume a correlation between in vitro and in vivo efficacy in the claimed compounds. The Court disagrees.
The only evidence supporting Teva’s argument is the testimony of Dr. Trummlitz. Dr. Trummlitz testified that the person of ordinary skill could have concluded that the compounds of the ’196 Application were anti-inflammatory despite the lack of in vivo data. He explained that the Fujis-awa ’142 Patent and WO 708 Patent both included in vitro and in vivo data for similar compounds, and that DuP 697 was known by 1993 to be anti-inflammatory and believed to be COX-2 selective. Based on this published data, Dr. Trum-mlitz asserted that “one could conclude that this type of compound will work.” (Trial Trans. IV 107:8-9.) He also stated:
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I think the general method, if we are working in a new area, if you have new compounds, you need very early the link between in [vitro] and in vivo. If you have already data showing good correlation, then it is not so important, you will do it later, the in vivo studies.
(Trial Trans. IV 107:9-13;
see also
Trial Trans. IV 109:24-114:21.)
The Court is not persuaded by this testimony. As an initial matter, COX-2 selective anti-inflammatory development was a “new area” in 1993. As the Patent Examiner who reviewed the T96 Application stated: “The discovery of COX-2 is a recent development in the art, as indicated in the instant specification, and relatively little is known about it and its properties.” (PTX 34 at PFC 02019556.) Thus, even according to Dr. Trummlitz’s own testimony, the person of ordinary skill would have needed to see the link between in vitro and in vivo activity at the time the 196 Application was filed.
Moreover, several of Pfizer’s witnesses testified that without in vivo data, the person of ordinary skill would not have known whether the compounds were anti-inflammatory. Dr. Jorgensen testified that the lack of in vivo data in the Application “means that the compounds that are disclosed are not necessarily anti-inflammatory,” and that “antiinflammatory [activity] would have to be determined in an in vivo experiment.” (Trial Trans. XVI 51:6-12.) Dr. Seibert, who spoke about her experiences on the team that developed celecox-ib, testified that not all compounds that “worked” in vitro were anti-inflammatory in vivo. She stated that they could not predict on the basis of in vitro data whether a compound would be active in vivo: “[Y]ou had to do the study. You could not predict.”
(Id.
XII 74:5-16.) Dr. Talley, another inventor of celecoxib, testified that even when a compound performed well in in vitro assays, he could not tell whether it would be anti-inflammatory until the compound was tested in a laboratory animal.
(Id.
XV 67:7-13.) Dr. Galbraith, who gave the presentation on DuP 697 at the Keystone conference, testified that anti-inflammatory activity must be determined based on in vivo studies and data.
(Id.
XVII 10:22-11:4 (explaining the need for “in vivo data where you actually had animal, experimental results showing that the compounds were antiinflammatory in nature”).) Indeed, even Dr. Wolfe' — one of Teva’s own medical experts — testified that in vitro and in vivo test results do not always match up. (Trial Trans. V 147:9-23.)
Finally, the Patent examiner who reviewed the T96 Application also agreed with this assessment. She rejected the Application on the ground that “there [was] insufficient proof that the inhibition of COX-2 would translate into anti-inflammatory activity.” PTX 34 at PFC 02019560;
see also
Trial Trans. XVI 51:16-52:24. Merck’s acquiescence in this rejection is the proverbial last nail in the coffin; the final piece of evidence that the disclosure of the T96 Application does not enable even its own claimed compounds.
Turning to step two of Teva’s argument as set forth above, the Court finds that even assuming the disclosure of the T96 Application would have enabled the person of ordinary skill to make and use the five examples, this would not have enabled a person of ordinary skill to make and use the entire scope of claim 6 of the ’995 Patent.
As discussed
supra,
the examples and supporting information in the T96 application do not cover the entire genus of claim 6. This is not always fatal to enablement of a claim, but as with the written description requirement, the amount of disclosure required to enable the full scope of a genus claim depends, in large part, on the degree
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of predictability in the relevant field. The Federal Circuit has highlighted the importance of unpredictability in evaluating the enablement of generic claims:
In unpredictable art areas, this court has refused to find broad generic claims enabled by specifications that demonstrate the enablement of only one or a few embodiments and do not demonstrate with reasonable specificity how to make and use other potential embodiments across the full scope of the claim. Enablement is lacking in those cases, the court has explained, because the un-described embodiments cannot be made, based on the disclosure in the specification, without undue experimentation.
PPG Indus., Inc. v. Guardian Indus. Corp.,
75 F.3d 1558, 1564 (Fed.Cir.1996) (internal citations omitted)
Given the unpredictability of pharmaceutical chemistry in general, and of COX-2 selectivity in particular, information and data on more than a handful of species was necessary to enable a person of ordinary skill to make and use the full scope of the genus claimed in claim 6 of the ’995 Patent without undue experimentation, and to be confident in its utility. Teva offers virtually no evidence in support of its conclusory statement that a person of ordinary skill would be able to generalize the information provided to cover the full scope of the claim. Teva once again cites to Dr. Trummlitz’s testimony reproduced in volume 4 of the transcript at 92:17-94:2 and 103:19-114:2. Having reviewed the cited testimony, the Court finds no persuasive explanation of how the disclosure of the 196 Application would enable all of the compounds of claim 6. The entirety of the testimony on this specific question seems to be as follows:
Q: How, if at all ... does the lack of any specific in vivo data impact your opinion that the 196 application provides support for the claims in the ’995 patent which you just identified!;?]
A: I think the claims of the ’995 patent are supported by the data in the 196 application.
Q: For the same reasons or different reasons?
A: For the reasons I mentioned before. Because the data are present. Which know what the correlation between in vitro and in vivo is.
(Trial Trans. IV 109:14-23.) This falls far short of persuasively explaining how the disclosure of the 196 Application enables the full scope of claim 6.
The Federal Circuit has explained that the written description requirement and enablement requirement “usually rise and fall together.”
LizardTech Inc. v. Earth Resource Mapping, Inc.,
424 F.3d 1336, 1346 (Fed.Cir.2005). This case is no exception.
[A] recitation of how to make and use the invention across the full breadth of the claim is ordinarily sufficient to demonstrate that the inventor possesses the full scope of the invention, and vice ver-sa. ... Whether the flaw in the specification is regarded as a failure to demonstrate that the patentee possessed the full scope of the invention recited in claim [6 of the ’995 Patent] or a failure to enable the full breadth of that claim, the specification provides inadequate support for the claim under section 112, paragraph one.
Id.
In sum, the Court finds that the en-ablement requirement for claim 6 of the ’995 Patent is not satisfied by the disclosure of the ’196 Application.
iv.
The T96 Application Does Not Violate the Best Mode Requirement
The final requirement of § 112 is that the application must “set forth the best mode contemplated by the inventor for
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carrying out his invention.” 35 U.S.C. § 112 . Pfizer contends that the “best mode requirement” is not met for claim 6 of the ’995 Patent. Specifically, Pfizer argues that Merck identified Vioxx as the best mode of the invention, but failed to disclose the compound in the ’196 Application.
The Court does not agree that the failure to disclose Vioxx in the T96 Application constitutes a violation of the best mode requirement. There is no evidence that Vioxx was the inventors’ preferred embodiment at the time the ’196 Application was filed. In the absence of a subjective preference
at that time,
there can be no best mode violation.
See Go Med. Indus. Pty., Ltd. v. Inmed Corp.,
471 F.3d 1264 , 1270 (Fed.Cir.2006).
v.
Summary of Claim 6
In sum, the Court finds that claim 6 of the ’995 patent was not fully supported by the disclosure of the ’196 Application since neither the written description nor enablement requirements were satisfied by the disclosure.
(c) Claim 15 of the ’995 Patent is Not Supported By the Disclosure of the ’196 Application
Teva contends that claim 15 of the ’995 Patent is fully supported by the disclosure of the ’196 Application. As with claim 6, the parties do not dispute the relevant facts, only the legal conclusions to be derived therefrom.
i.
Undisputed Facts
Claim 15 of the ’995 Patent is a Markush claim that lists 36 compounds. (PTX 17, at col. 76.) The first two compounds of Markush claim 15 of the ’995 Patent are the same as the compounds of examples 9 and 10 of the ’196 Application. As explained above, the T96 Application also includes data and synthesis methods for these two compounds. The other 34 compounds are not disclosed anywhere in the T96 Application. Teva claims that § 112 support for the first two compounds of Markush claim 15 is sufficient to describe and enable the entire claim. Pfizer disagrees and further argues that the ’196 Application fails to provide adequate support for even those first two compounds.
ii.
Adequate Section 112 Support for Markush Claims
“A Markush group is a listing of specified alternatives of a group in a patent claim.”
Abbott Labs. v. Baxter Pharm. Prods.,
334 F.3d 1274, 1280 (Fed. Cir.2003). Markush claims usually cover a family of compounds by defining the structure common to all members, as well as one or more alternatives selected from a set consisting of named chemical compounds. A letter, most often the letter “R,” is typically used to represent the set of alternatives. Roger Schechter and John Thomas,
Principles of Patent Law
217 (2d ed). For example: “A compound of the formula OH — CH—R, where R is selected from the group consisting of chlorine, bromime, and iodine.”
Id.
Although this simple example neatly illustrates the Markush format, it may not fully convey the desirability of this type of claim. In this case, if the Mar-kush format were unavailable an inventor could simply three draft claims individually reciting chlorine, bromime and iodine. But in the real world of chemistry the relevant alternatives often constitute chemical radicals that may themselves consist of hundreds of closely related compounds. Inventors in such fields as pharmacology ... would be sorely pressed if required to draft dozens or hundreds of claims to define
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each and every member of the alternative group.
Id.
Teva claims that a Markush group is fully supported as long as there is adequate § 112 support for even one member of the Markush group. Pfizer vigorously disputes this proposition, and contends that Markush claims require support for each member of the Markush group. There is little caselaw on this question. Indeed, there is little caselaw on Markush claims in general. Given that over 1,000 patents with Markush claims issue in the United States every year,
18
one would expect this to be a common issue with a settled answer. However, this is not the case. Pfizer and Teva direct the Court to one case each. In an independent search of the caselaw, the Court was unable to find any other relevant cases and virtually no guidance in treatises or other texts.
Teva relies on
Ex parte Ebata,
19 U.S.P.Q.2d 1952 , 1991 WL 326561 (Bd. Pat.App. & Inf.1991). Ebata filed a patent application on June 10, 1981. This application was followed by a series of CIP applications, the last of which — No. 07/045,775 (the “ ’775 Application”)' — was filed on April 29, 1987. The patent examiner rejected the application as obvious over several prior art references, including U.S. Patent No. 4,761,426 (the “Martin Patent”). Ebata appealed.
The Martin Patent also resulted from a series of continuation and continuation-in-part applications culminating with application No. 06/643,763 (the “ ’763 Application”), which was filed on August 24, 1984. The Martin Patent issued from the ’763 Application on August 2, 1988. For the sake of clarity, the various applications that led to the Martin and Ebata Patents are listed in the chart below.
[[Image here]]
The Board of Patent Appeals began its opinion by stating that
“if
the Martin patent constitutes legally available prior art in this case, the relevant subject matter disclosed by Martin anticipated claim 23 within the meaning of 35 U.S.C. 102.”
Id.
at 1954 , 1991 WL 326561 . The Board then turned to what it considered the “real question,” “whether and to what extent Martin constitutes legally available prior art under 35 U.S.C. 102(e).”
Id.
In this regard, the Board had to determine whether the Martin Patent was entitled to claim priority to the October 8, 1980 filing date of its (grand)parent application. Only if it was entitled to that date would it be available as prior art.
Id.
Claim 2 of the Martin Patent was a Markush claim covering four salt forms of
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lysocellin. The Board held that the Mar-kush claim was full supported by the ’722 Application, which disclosed one of the four salt forms.
Id.
at 1955 , 1991 WL 326561 (“[T]he specific recitation of the manganese salt or complex is fully described within the meaning of 35 U.S.C. 112, first paragraph, in grandparent application Serial No. 06/196/722.”). The Board explained its reasoning as follows:
Bear in mind that the Markush group of claim 2 is merely an arbitrary subgenus covering four salt forms of lysocellin .... This is tantamount to claiming the administration of each salt form or embodiment separately in separate claims. It would elevate form over substance to hinge a legal conclusion, respecting availability of the Martin patent as a reference, on whether Martin set forth four separate claims directed to patentable salt forms or, as in claim 2 here, set forth a Markush group covering the four embodiments alternatively.
Id.
Pfizer, meanwhile, relies on
In re Fouche,
58 C.C.P.A. 1086 , 439 F.2d 1237 (1971), to support its position that
all
members of a Markush group must have adequate § 112 support. In
Fouche ,
the inventors claimed “a class of compounds having pharmaceutical utility due to their antidepressant, neuroleptic and tranquilizing properties.”
Id.
at 1238. The Patent Office rejected claims 1-3 of the application, and the Board of Patent Appeals affirmed the rejection. Claim 1 was a Markush claim covering a range of compounds:
1. A dibenzo [a, d] cycloheptadiene derivative of the formula:
[[Image here]]
and its acid addition salts and quaternary ammonium derivatives in which A is a divalent, saturated aliphatic hydrocarbon chain of 2 to 5 carbon atoms, such that at least 2 carbon atoms separate the radical Z from the dibenzocyclo-heptadiene ring, and Z is a member selected from the group consisting of amino, monoalkylamino, dialkylamino, in which the alkyl radicals contain 1 to 5 carbon atoms each, and 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, and 4-alkyl-l-piperazinyl in which the alkyl radical contains 1 to 5 carbon atoms, and such rings substituted by at least one alkyl radical of 1 to 5 carbon atoms each.
The Patent Examiner rejected this claim on the ground of insufficient disclosure under § 112. The Examiner noted that the definition of “Z” in the claim was by a Markush group including both aliphatic and heterocyclic members, and found that the specification did not enable use of compounds within the claim having heterocyclic moieties.
Id.
at 1242. None of the examples included compounds wherein Z was heterocyclic.
Id.
The Court agreed that the application failed to teach a person of ordinary skill how to use the hetero-cyclic members and affirmed the PTO’s rejection of claim 1. The Court stated:
It seems clear, and it is not disputed by appellant, that where an applicant undertakes to define his invention by the recitation of a Markush group, he must enable one of skill in the art to make
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and use at least one composition employing each member of the Markush group.
Id.
Both parties offer various interpretations of the cases and attempt to distinguish the unfavorable opinion on various grounds — none of which the Court finds particularly persuasive. The Court need not resolve this complicated question because the evidence does not establish that even the first two compounds of Markush claim 15 are fully supported by the disclosure of the ’196 Application.
iii.
The ’196 Application Does Not Enable the First Two Compounds of Claim 15 of the ’995 Patent
Since compounds 1 and 2 of claim 15 are expressly disclosed in the ’196 Application, there can be no dispute that the written description requirement is met with respect to those specific compounds. The enablement requirement, however, if not satisfied even with respect to these two particular compounds. As discussed in detail in Section I.B.l(b), given the lack of in vivo data in the ’196 Application, the person of ordinary skill would not know whether examples 9 and 10 (which are compounds 1 and 2 of claim 15) were anti-inflammatory. Since the Application fails to establish the practical utility of those compounds, it also fails to enable them under § 112. Thus, even under Teva’s interpretation of the law, claim 15 of the ’995 Patent is not fully supported by the disclosure of the ’196 Application because the enablement requirement is not satisfied.
(d) Conclusion Regarding the ’196 Application/’995 Patent
Since neither claim 6 nor claim 15 or the ’995 Patent are fully supported by the disclosure of the 196 Application, the ’995 Patent is not entitled to the June 24, 1993 filing date of the 196 Application. Accordingly, the 196 Application/ ’995 Patent is not prior art to the patents-in-suit.
2. The ’829 Application Is Prior Art to the Patents-in-Suit
The Fujisawa ’829 Application was published on August 11, 1993. Pfizer initially argued that the ’829 Application was not prior art to the patents-in-suit because celecoxib was invented on August 2, 1993 — nine days prior to this reference date. As discussed above, Pfizer has abandoned this argument and the Court has established the invention date to be October 4, 1993.
See supra
Section I.A. Accordingly, the ’829 Application is proper prior art.
C.
The Level of Ordinary Skill in the Prior Art
The second
Graham
factor is the level of ordinary skill in the prior art. The obviousness analysis is conducted from the perspective of a person at that skill level. 35 U.S.C. § 103 (a). This hypothetical person of ordinary skill is an objective legal construct who is presumed to be aware of all the relevant prior art.
Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc.,
807 F.2d 955, 962 (Fed.Cir.1986).
While the person having ordinary skill knows all of the prior art, s/he is neither a genius nor an innovator. “A person of ordinary skill in the art is also presumed to be one who thinks along the line of conventional wisdom in the art and is not one who undertakes to innovate, whether by patient, and often expensive, systematic research or by extraordinary insights, it makes no difference which.”
Standard Oil Co. v. Am. Cyanamid Co.,
774 F.2d 448, 454 (Fed.Cir.1985);
see also Life Techs., Inc. v. Clontech Labs., Inc.,
224 F.3d 1320, 1326 (Fed.Cir.2000).
The parties in this case dispute the appropriate educational background of the person having ordinary skill in the art.
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Pfizer argues that such a person would have a bachelor’s or master’s degree in chemistry or a related science and several years of experience at a pharmaceutical or biotechnology company. Teva claims that the person of ordinary skill would have a Ph.D. in chemistry or a related science plus several years of experience. “The dispute appears to be somewhat academic (so to speak).”
Janssen Pharmaceutica N.V. v. Mylan Pharms., Inc.,
456 F.Supp.2d 644, 653 (D.N.J.2006). Neither party contends that the educational background of the person of ordinary skill is determinative of whether the patents-in-suit are obvious or not. Additionally, neither party provided evidence on how specific prior art references in the record would have been viewed differently depending upon the educational background of the person of ordinary skill.
Furthermore, it appears that few courts conducting an obviousness analysis ever specify the exact level of ordinary skill in the art. In the opinion of one authority, this is because, “[i]n practice, the concept of ‘a person of ordinary skill in the art’ seems more designed to remind judges to put themselves in the shoes of a skilled artisan, rather than to compel a specific factual finding.” Roger Schechter
&
John Thomas,
Principles of Patent Law,
§ 5.3.2.2 (2d ed.2004).
To the extent that it matters, the Court agrees with Pfizer that the person of ordinary skill would have a bachelor’s or master’s degree in chemistry or a related science and several years experience working in the relevant field. Pfizer’s expert in pharmaceutical chemistry so testified (Trial Trans. XVI 50:11-19), and one of the inventors of celecoxib testified that only half the people on the team that developed celecoxib had Ph.D.s. The other half had a bachelor of science or master’s degree in chemistry or a related science.
(Id.
XV 45:6-13.) Although both of Teva’s chemistry experts testified that the person of ordinary skill would have had a Ph.D., the Court finds the combination of hypothetical and real world testimony presented by Pfizer’s witnesses to be more persuasive.
19
Pfizer also argues that Teva’s person of ordinary skill is, contrary to law, someone who invents. Pfizer relies in part on the testimony of one of Teva’s expert witnesses, Dr. Baker, who stated that he derived the pharmacophore through the use of his own intuition. The Court does not find this to be persuasive evidence. “Intuition” is not synonymous with “invention.” A comparison of the definitions of the two words is illustrative.
• “Intuition” is defined as “the act or process of coming to direct knowledge or certainty without reasoning or inferring,” “immediate cognizance or conviction without rational thought,” and “immediate apprehension or cognition.”
Webster’s Third New International Dictionary
1187 (1993).
• “Invention,” by contrast, is defined as “the power to conceive new ideas and relationships,” “a faculty for creative selection of theme and imaginative treatment of design or content,” and “a product of thought or mental synthesis.”
Id.
at 1188.
Accordingly, the Court does not interpret Dr. Baker’s statement regarding his use of intuition as a concession that Teva’s person of ordinary skill is one who invents.
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Pfizer also relies on testimony of Teva’s experts that the person of ordinary skill is “trying to get a patent,” and makes choices with the goal of avoiding prior art and creating a patentable invention. This issue is addressed below in the context of the specific
choices
— ie., steps in Teva’s obviousness theory- — that are predicated on that goal.
D.
The Differences Between the Claimed Invention and the Prior Art
Assuming
arguendo
that the ’196 Application/’995 Patent is prior art, Teva still has to prove that the claimed invention is obvious in light of this and other prior art references. As explained above, a
prima facie
case of obviousness exists with respect to a chemical compound if there is “structural similarity between claimed and prior art subject matter ... [and] the prior art gives reason or motivation to make the claimed compositions.”
In re Dillon,
919 F.2d 688, 692 (Fed.Cir. 1990) (en banc). Here, the chemical compound at issue is celecoxib. The chemical structure of celecoxib can be pictorially depicted as follows:
[[Image here]]
Teva’s theory of the obviousness of cele-coxib involves many steps, all of which must be proven by clear and convincing evidence.
See Takeda Chem. Indus., Ltd. v. Mylan Labs., Inc.,
417 F.Supp.2d 341, 347 (S.D.N.Y.2006) (stating that when a theory of obviousness “requires the chemist to pursue several steps in manipulating a compound revealed in the prior art, the patent challenger must show that one of ordinary skill in the art would have had sufficient motivation to take
each of those steps.”)
(emphasis added). Teva contends that on October 4, 1993, a person of ordinary skill would have taken all of the following steps: (1) selected the ’196 Application as a starting point; (2) devised the hypothetical pharmacophore proposed by Teva’s experts; and (3) combined the teachings of the ’196 Application and the T42 Patent with a knowledge of pharmacological principles to arrive at the twelve allegedly obvious compounds. Each of these steps involves several sub-steps, all of which must also be proven by clear and convincing evidence for Teva to successfully establish a
prima facie
case of obviousness. If the person of ordinary skill would not have taken even one of the asserted steps, Teva’s obviousness defense must fail. Although Teva proved some of these sub-steps, the Court finds that Teva’s obviousness argument fails at every major crossroad.
The Court also notes at the outset that it found the testimony of Pfizer’s expert witness, Dr. Jorgensen, to be more comprehensible, comprehensive, persuasive, and credible than the testimony of either of Teva’s chemistry experts, Dr. Baker or Dr. Trummlitz. Although all three experts are eminently well-qualified, the Court found Dr. Jorgensen’s testimony to be un
*425
derstandable, logical, and compelling. Dr. Trummlitz’s testimony, by contrast, was extremely difficult to follow. Both Drs. Baker and Trummlitz frequently hurried over complicated issues and — even after prodding from the Court — failed to provide detailed explanations of their opinions and the bases therefor.
Moreover, specific aspects of Drs. Baker and Trummlitz’s testimony cast doubt on their credibility. As discussed in more detail herein, Dr. Baker provided internally inconsistent testimony with respect to the exclusion of a carbon, carbon double bond from the pharmacophore,
see infra
Section I.D.2(d), and offered post-hoc rationalizations to explain his failure to consider certain references,
see infra
Section I.D.l(c), n. 19. Dr. Trummlitz testified that the person of ordinary skill would have made choices based on the excessive half-life of DuP 697 without any actual knowledge of whether that information was known in 1993,
see infra
Section I.D.3(d), and asserted that he made an error in his expert report when it became clear that the analysis laid out in his report could not have led to the development of celecoxib,
see infra
Section I.D.3(e). In addition to these examples, which are discussed in context below, Dr. Trummlitz supplemented the opinions articulated in his expert report in order to respond to issues raised in Dr. Baker’s cross-examination, which Dr. Trummlitz observed.
20
Finally, Dr. Trummlitz asserted at trial that the person of ordinary skill would not have attempted to innovate; however, when he was asked at his deposition whether the person of ordinary skill tried to innovate, his response was “Sure. That’s why he is hired.” (Trial Trans. VII 177:23-178:19.)
Based on all of these considerations, the Court finds Pfizer’s chemistry expert to be more credible and more persuasive than Teva’s chemistry experts. This finding colors the Court’s view of the entire case, and underlies — even when not explicitly mentioned' — -many of the Court’s impressions and decisions.
1. The Person of Ordinary Skill Would Not Choose the T96 Application/’995 Patent As the Starting Point for Developing New NSAIDs
Even assuming
arguendo
that the T96 Application is prior art to the patents-in-suit, the Court finds that the person of ordinary skill would not select it as the starting point for his/her efforts. One thing the parties essentially agree on is that the problem to be solved was the development of a new NSAID without serious GI side effects. The parties disagree, however, about what the person of ordinary skill would have chosen as the starting point for solving this problem.
Teva argues that the person of ordinary skill would have searched the prior art for references that disclosed COX-2 selective compounds because s/he would have ex
*426
pected those compounds to be anti-inflammatory and gastric sparing. Among the references disclosing COX-2 selective compounds, the person of ordinary skill would have preferred those that included enough information to derive a pharmaco-phore. Teva contends that using these parameters, the person of ordinary skill would have selected the ’196 Application as his/her starting point because it was the only reference that disclosed a series of COX-2 selective compounds from which a person of ordinary skill could have derived a pharmacophore for COX-2 selectivity.
Pfizer argues that the person of ordinary skill would not have limited his/her search to COX-2 related art, and even if s/he did so limit the search, would not have selected the ’196 Application as the starting point because flaws in the Application made it inferior to other potential leads. Specifically, Pfizer contends that the person of ordinary skill would not have reasonably expected the compounds of the ’196 Application to be anti-inflammatory in vivo, and would have preferred to start with a compound (or group of compounds) with proven in vivo activity such as DuP 697 or NS-398.
For the reasons discussed below, the Court finds that Teva has failed to prove by clear and convincing evidence that the person of ordinary skill would have selected the T96 Application as the starting point for developing a new NSAID with reduced GI side effects.
(a) The Person of Ordinary Skill Would Not Have Limited the Search to COX-2 Selective Compounds
Pfizer first argues that the person of ordinary skill would not have limited his/ her search to COX-2 selective inhibitors. Teva contends that the person of ordinary skill would have limited the search to such compounds because by 1993, s/he would have understood that COX-2 selective inhibition was the most promising approach to solving the problem at hand. In support of its position, Teva points out that Pfizer created an entire project devoted to identifying COX-2 selective NSAIDs.
While it is certainly true that Pfizer allocated significant resources to this project, Pfizer scientists pursued several other approaches during this time as well. For example, in the early 1990s, Pfizer scientists were investigating the possibility of developing a “steroid like drug” that would inhibit the conversion of genes to COX-2 enzymes — i.e., inhibit the synthesis of COX-2 entirely. (Trial Trans. XII 63:9-65:7; PTX 2400.) Although Pfizer shifted more resources into the COX-2 selective NSAID project following the Keystone Conference, it continued working on other approaches as well. Similarly, other companies looking for gastric-sparing anti-inflammatory compounds were also investigating several different pathways.
(Id.
at XVII 8:2-10:12; PTX 2501.) These approaches were still being actively pursued in 1993 because scientists were not confident that they would be able to develop a compound that selectively inhibited COX-2.
Accordingly, the Court finds that Teva has failed to prove that the person of ordinary skill would have focused his/her search exclusively on COX-2 selective compounds.
(b) Teva Has Not Established That the Person of Ordinary Skill Would Have Reasonably Expected the Compounds of the T96 Application to Be Anti-Inflammatory
Pfizer’s next argument is that even if the person of ordinary skill searched only COX-2 related art, s/he would not have selected the ’196 Application as the starting point because s/he would not have ex
*427
pected the compound to be anti-inflammatory. Pfizer contends that due to the lack of in vivo data in the ’196 Application, the person of ordinary skill would not have known whether the compounds possessed the desired anti-inflammatory activity. Several of Pfizer’s witnesses testified to this effect.
21
(See, e.g.,
Trial Trans. XVI 51:6-12; XII 74:5-16; XV 67:7-13; XVII 10:22-11:4;
see also supra
Section I.B.l(b).)
Teva vigorously disputes this assertion and contends that the person of ordinary skill would have concluded, based on the disclosure and teaching of the ’196 Application, that the compounds disclosed therein were anti-inflammatory in vivo.
22
Specifically, Teva points to the fact that the application discloses the rat paw edema assay (a standard in vivo assay for determining anti-inflammatory activity), describes it in the past tense, and states that the compounds are anti-inflammatory.
See
DTX 302 at 10 (“The Compound of Formula I is useful for the relief of pain, fever and inflammation of a variety of conditions .... ”);
Id.
at 44 (“Rat Paw Edema — Protocol”).
With respect to the rat paw edema assay, the ’196 Application states:
Assays for Determining Biological Activity
The compound of formula I can be tested using the following assays to determine their cyclooxygenase-2 inhibiting activity.
Inhibition of Cyclooxygenase Activity
Compounds were tested as inhibitors of cyclooxygenase activity in whole cell and microsomal cyclooxygenase assays. Both of these assays measures prosta-glandin E2 synthesis in response to ara-chidonic acid, using radioimmunoas-say. ...
Rat Paw Edema Assay
— Protocol
Male Sprague-Dawney rats (150-200 g) were fasted overnight and were given po either vehicle (1% methocel) or a test compound. One hr later, a line was drawn using a permanent marker at the level above the ankle in one hind paw to define the area of the paw to be monitored. The paw volume (V0) was measured using a plethysmometer (Ugo-Basile, Italy) based on the principle of water displacement. The animals
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were then injected subplantarly with 50 SI of 1% carrageenan solution in saline (FMC Corp., Maine) into the paw using an insulin syringe with a 25-gauge needle (i.e. 500<tg carrageenan per paw). Three hr later, the paw volume (V3) was measured and the increases in paw volume (V3 — V0) were calculated. The animals were sacrificed by C02 asphyxiation and the absence or presence of stomach lesions scored. Data were compared with the vehicle-control values and percent inhibition calculated. Since a maximum of 60-70% inhibition (paw edema) was obtained with standard NSAIDs, ED30 values were used for comparison. All treatment groups were coded to eliminate observer bias.
(DTX 302 at 44.) This section of the Application also includes “representative biological data” from the in vitro test to evaluate “inhibition of cyclooxygenase activity” referred to above.
(Id.
at 11, tbl. III.) As for the rat paw edema assay, there is no data, no summary of the results, no further discussion at all.
Mr. Smith, Teva’s expert on Patent Office practice and procedure, testified that there is an understanding in the PTO that “applicants are not to use the past tense unless the work has already been done. In fact, if they use the past tense indicating that work had been done when in fact it was a prophetic example and work had not been done, that would be considered to be misleading [t]o the Patent Office. It would be inappropriate.” (Trial Trans. XI 69:13-22.) Thus, according to Teva, the description of the rat paw edema assay in the past tense shows that the test was done, and, coupled with the statement that the compounds are anti-inflammatory, would have led the person of ordinary skill to reasonably expect that the compounds were, in fact, anti-inflammatory in vivo.
Pfizer has several issues with Teva’s theory. First, the description is captioned a “protocol,” and does not mention any particular compounds being tested. Second, the description is in a section called “Assays for Determining Biological Activity,” which begins with the general statement that “[t]he compound of Formula I
can be tested
using the following assays .... ” (DTX 302 at 10 (emphasis added).) Third, when compounds were actually tested in an assay described in the section — as with the “Inhibition of Cyclooxygenase Activity” test — the inventors explicitly stated that “compounds were tested,” and provided data on the results obtained.
The Court admits that it finds this issue hard to resolve. Both parties raise legitimate points with respect to the proper interpretation of the language of the “Rat Paw Edema Assay — Protocol.” On the one hand, the use of the past tense certainly implies that the test was actually done, and it would be both odd and improper to phrase the section that way if the test were not done. On the other hand, the use of the phrase “protocol,” the lack of any data or results, and the differences between the description of the in vitro and in vivo tests (e.g., failure to state that “compounds were tested”) imply — at best — that the test was not done. At worst, the person of ordinary skill could infer from lack of data that the test was done and the results did not support a finding that the compounds were anti-inflammatory.
Accordingly, the resolution of this issue turns on the burden of proof. It is Teva’s burden to prove its assertion that the person of ordinary skill would have selected the T96 Application as the starting point for the development of new NSAIDs because s/he would have reasonably expected the compounds to be gastric sparing and anti-inflammatory. This Teva has not done. Especially in light of the existence of other possible leads (discussed in Section D.l(e), below) that were known to be
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both COX-2 selective and anti-inflammatory, the Court finds that Teva has failed to meet its burden of proof on this issue.
(c) Better Leads Were Available to the Person of Ordinary Skill to Begin Development of New NSAIDs
Pfizer has proffered several other potential starting points, namely DuP 697, NS-398, Merck Patent No. 5,604,260 (the “ ’260 Patent”), and Merck Patent No. 5,436,265 (the “’265 Patent”). The Court will discuss these potential leads in turn.
i.
’260 Patent and ’265 Patent
Pfizer argues that the person of ordinary skill could have started with the ’260 Patent or the ’265 Patent. The ’260 Patent states that the disclosed compounds are COX-2 selective, and provides data and instructions for synthesizing the compounds. The ’265 Patent contains a list of representative embodiments of the invention, which the Patent claims are COX-2 selective. Thus, they would appear to be promising leads.
However, the filing date for the ’260 Patent was November 4, 1993 and the filing date for the ’265 Patent was November 12, 1993. Since both of these dates are after the invention date for the patents-at-issue, which the Court has found to be October 4, 1993
(see supra
Section I.A), neither the ’260 nor the ’265 Patents were available to the person of ordinary skill as of the date of invention and therefore cannot be considered for the purpose of determining whether the person of ordinary skill would have started with the T96 Application.
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ii.
DuP 697 and NS-398
Pfizer also argues that the person of ordinary skill could have started with DuP 697 or NS-398. Teva concedes that the available literature in October 1993 identified DuP 697 and NS-398 as displaying COX-2 selectivity in vitro and having anti-inflammatory activity in vivo. However, both Dr. Baker and Dr. Trummlitz testified that the person of ordinary skill would have preferred to start with the ’196 Application because neither DuP 697 nor NS-398 could provide as much information as the numerous examples disclosed in the ’196 Application concerning which elements were important to achieving COX-2 selectivity. (Trial Trans. I 116:6-23; III 130:8-21; 124:12-125:5.) In other words, both experts said that the person of ordinary skill could build a better pharmaco-phore from the multiple examples of the T96 Application than from DuP 697 or NS-398.
Pfizer disputes the idea that the person of ordinary skill would have preferred to work from a pharmacophore rather than an individual lead compound. It cites Dr. Jorgensen’s testimony that “most individu
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als practicing medicinal chemistry prefer to work from a lead compound.” (Trial Trans. XVI 105:22-106:3.) Pfizer also argues that in a field where the COX-2 in vitro assays were new and less understood than well-established in vivo assays, the person of ordinary skill would have clearly preferred to start with a lead compound with demonstrated in vitro and in vivo activity, rather than to create a pharmaco-phore based solely on in vivo data. The Court finds the last point quite persuasive. Regardless of whether an inventor would generally prefer a single lead compound or a pharmacophore, it would be logical for the person of ordinary skill to prefer a single compound known to have all the desired properties over a pharmacophore derived from compounds that may or may not have those properties.
Furthermore, DuP 697 and NS-398 were both covered by patents that contained additional examples of compounds. Dr. Trummlitz testified that the person of ordinary skill could derive a pharmaco-phore from these patents, but that it would be different from the hypothetical pharma-cophore proposed in this case and would not lead the person of ordinary skill to celecoxib. (Trial Trans. VII 71:7-73:20 (NS-398); VII 73:21-75:21 (DuP 697);
see also
PTX 913 (patent covering NS-398).)
After being questioned about these two patents on cross examination, Dr. Trum-mlitz testified on re-direct that he did not use the patent covering NS-398 because it did not include COX-1 or COX-2 data. He offered no explanation as to why the person of ordinary skill would not use the patent covering DuP 697.
Taking all of this into consideration, the Court is not persuaded that it is “highly probable” that the person of ordinary skill would choose the ’196 Application as the starting point for developing new NSAIDs.
Buildex, Inc. v. Kason Indus., Inc.,
849 F.2d 1461, 1463 (Fed.Cir.1988). Accordingly, Teva has not met its burden of proving by clear and convincing evidence that the ’196 Application was the appropriate starting point for the development of new NSAIDs.
2. The Person of Ordinary Skill Would Not Derive The Hypothetical Pharmacophore From the Teachings of the ’196 Application
Even if the ’196 Application/’995 Patent is prior art to the patents-in-suit and the person of ordinary skill would have selected it as the starting point, Teva has not proven that the person of ordinary skill would derive the hypothetical pharmaco-phore from the disclosure of the Application. A pharmacophore is a “core structure ... drawn from a series of biological data ... [which] summarizes the basic features which might lead to [the desired activity.]” (Trial Trans. I 108:23-25.) Dr. Baker testified that pharmacophores are commonly used in the development of new pharmaceuticals. Both Dr. Baker and Dr. Trummlitz testified that the person of ordinary skill would have derived the following pharmacophore from the examples disclosed in tables 1 and 2 of the T96 Application, and would have reasonably expected compounds within the pharmaco-phore to be COX-2 selective:
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[[Image here]]
Essentially, Teva argues that the person of ordinary skill would have derived this pharmacophore because almost all of the 71 example compounds in the T96 Application contain 5-membered heterocycles, have a methylsulfonyl or sulfonamide sub-stituent on the 4-position of one of the phenyl rings, and have two phenyls attached to the heterocycle in adjacent positions. (Trial Trans. 1114:12-22; 1116:6-23; III 124:12-126:1.) Pfizer vigorously disputes that the person of ordinary skill would have derived this pharmacophore. Pfizer argues that the pharmacophore is too broad in some respects, too narrow in others, and the result of impermissible hindsight. Specifically, Pfizer raises four arguments with respect to Teva’s hypothetical pharmacophore: (1) the person of ordinary skill would not have focused exclusively on the examples; (2) Teva’s experts ignored several examples in creating the pharmacophore; (3) the pharmaco-phore should not permit the use of any heterocycle; and (4) the pharmacophore should require the six membered rings to be attached to the heterocycle via a carbon, carbon double bond. The Court will address each of these arguments in turn.
(a) The Person of Ordinary Skill Would Focus on the Examples
Although Pfizer seems to have abandoned this argument, Pfizer initially argued that the person of ordinary skill would not have focused on the examples and representative compounds to the exclusion of the genus disclosed in the ’196 Application. The Court disagrees. Dr. Baker and Dr. Trummlitz both testified that the person of ordinary skill would, in fact, focus primarily on the examples. Moreover, Pfizer’s own medicinal chemistry expert, Dr. Jorgensen, testified that in building a pharmacophore, the person of ordinary skill “would rely heavily on the examples in table one, the additional structures in table 2 and also be cognizant of the data that is in table three.” (Trial Trans. XVI 56:1-4.)
Accordingly, the Court is persuaded that the person of ordinary skill would focus on the examples provided in the ’196 Application, and not on the broader genus disclosed therein.
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(b) Exclusion of Some Examples From the Pharmacophore Was Appropriate
Pfizer’s second issue with the hypothetical pharmacophore is that Teva’s experts ignored three of the fourteen examples with data in table 1 when deriving the pharmacophore. Example 7 used a non-heterocycle as the five-membered ring. Example 4 used a cyclohexane, rather than a phenyl ring, as one of the six-membered rings. Example 14 used an acylsulfonam-ide, rather than a sulfonamide or methyl-sulfone, as the A-phenyl substituent. Therefore, Pfizer argues, the pharmaco-phore is too narrow and should include heterocycles and non-heterocycles, phenyls and cyclohexanes, and aeylsulfonamides.
Teva’s experts offered two explanations for their failure to include these examples in the pharmacophore. First, Teva’s experts testified that it was unnecessary to include these variations in the pharmaco-phore because they were essentially the same as the elements that were included. As for examples 4 and 14, Dr. Baker testified that a cyclohexane is “quite equivalent to a phenyl group,” (Trial Trans. II 96:20-97:4), and that an acylsulfonamide is a labile group, which will quickly form a “grouping equivalent to a sulfonamide group,”
(Id.
at II 101:22-102:4).
Dr. Baker’s explanation regarding example 7 is more complex, but essentially expresses the same idea: the non-heterocyclic example did not have to be included because it would act the same way as the heterocyclic examples. He explained his reasoning as follows. In both the hetero-cyclic and non-heterocyclic examples, the phenyl rings were situated on adjacent carbon atoms that were connected by a double bond. As the person of ordinary skill would have known, the carbon, carbon double bond in the heterocyclic examples would cause the central ring to be flat. This, in turn, would situate the phenyls in distinct and proper positions. Similarly, the person of ordinary skill would have known that in the non-heterocyclic example, the “double bond [would be] flat[,] exactly the same as th[e] heterocycle is flat. Therefore, the two phenyl groups situated on that double bond are in the same orientation as from the [heterocy-cle].”
(Id.
at II 100:9-12; II 97:3-100:12.)
In other words, Dr. Baker asserted that the carbon, carbon double bond was the essential feature that ensured the phenyl rings were placed in the correct orientation — whether the ring was heterocyclic or not. A non-heterocycle with a carbon, carbon double bond would act the same way as a heterocycle with a carbon, carbon double bond to position the phenyl rings in the appropriate position. “Therefore, although this molecule was not included in the pharmacophore, it really doesn’t negate anything about the pharmacophore, and in fact a man skilled in the art would understand that this molecule would be within this pharmacophore if he needed to consider that in the future.”
(Id.
at II 100:12-17.)
The Court is not persuaded by this explanation. In fact, this explanation seems to hurt Teva’s ease more than it helps it. If the excluded examples are the same as the included examples, and they are — as Dr. Baker asserted — implicitly within the pharmacophore, then there was no reason not to explicitly draw them into the figure, other than thinly-veiled hindsight and an attempt to narrow the options to arrive at celecoxib. Indeed, including them would benefit the person of ordinary skill by expanding the pool of possible options in which to pursue further development and testing.
Teva’s second explanation is more persuasive. Teva’s second explanation is that the inclusion of these examples would have meant including exceptions to the teach
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ings of the T96 Application. According to Teva, the person of ordinary skill would not have included such “outliers.” Rather, as a matter of standard practice, s/he would have looked for and included only the majority teaching of the Application. The Court agrees.
Dr. Baker testified that “when one examines a patent of this sort ... one takes the main information one can gain.” (Trial Trans. I 117:4-9.) Moreover, Dr. Talley, one of the inventors on the patents-in-suit, submitted a declaration to the PTO in connection with another patent application. In the declaration, he reviewed and analyzed the teachings of the Fujisawa ’142 Patent. He concluded that the Patent taught the use of a 5,1 configuration, rather than a 1,5 configuration, because 199 of 204 compounds with a sulfur containing substituent had a 5,1 configuration. (DTX 32 at PFC 01561786-89.) Dr. Talley testified at trial that he believed this was an appropriate analysis of the ’142 Patent and its teachings. (Trial Trans. XV 92:17-95:10.) This supports Teva’s assertion that the person of ordinary skill would follow the majority teaching of a reference and disregard “exceptions” to that general trend.
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Pfizer offered no contrary evidence indicating that all examples or available information must be included in a pharmaco-phore. Dr. Jorgensen did testify that all of the examples should have been included, but these conclusory statements are not sufficient to overcome the testimony of Dr. Baker and Dr. Talley relied on by Teva.
Accordingly, since only 2 of the 71 examples in the ’196 Application included a non-heterocycle, only 4 of the examples include a non-phenyl, and only 1 of the examples uses a substituent other than a sulfonam-ide or methylsulfone, it was not inappropriate for Teva’s experts to exclude these “outliers” from the hypothetical pharmaco-phore.
(c) Inclusion of Unlisted Heterocycles Was Not Appropriate
The hypothetical pharmacophore proposed by Teva’s experts permits any one of approximately fifty heterocycles to be used. Pfizer contends that this aspect of the pharmacophore is unduly broad. The examples of the ’196 Application disclose only eight different heterocycles, and the genus claim explicitly states that the het-erocycle should be selected from a list “consisting of’ twenty-seven possible het-erocycles. (PTX 34 at PFC 02019268-72.) “The phrase ‘consisting of is a term of art in patent law signifying restriction and exclusion.”
See Vehicular Techs. Corp. v. Titan Wheel Int’l, Inc.,
212 F.3d 1377 , 1382-83 (Fed.Cir.2000). In other words, “consisting of’ means these-and-only-these-options.
See Norian Corp. v. Stryker Corp.,
363 F.3d 1321, 1331 (Fed.Cir. 2004) (“ ‘Consisting of is a term of patent convention meaning that the claimed invention contains only what is expressly set forth in the claim.”). Thus, Pfizer argues that the pharmacophore should be limited to those heterocycles actually listed in the ’196 Application. Importantly, pyra-zoles — -the heterocycles used in celecoxib—
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are not among the possibilities listed or disclosed in the ’196 Application. Therefore, if the pharmacophore were limited to the listed heterocycles, it would be impossible to arrive at celecoxib.
Pfizer’s argument has significant intuitive appeal. Merck could have included a broader range of heterocycles in its ’196 patent application. It did not. It selected specific heterocycles and excluded others. Common sense dictates that the person of ordinary skill would have assumed that this choice was made for a reason, that the excluded heterocycles would not act in the same way, and that they should not be included in the pharmacophore.
Teva raises three points in opposition to this argument. The Court does not find any of them to be persuasive.
First, Teva argues that ’196 Application does not “teach away” from pyrazoles or other unlisted heterocycles:
Nothing in the Merck ’196 application would have provided a disincentive to using a pyrazole. It is silent regarding pyrazoles. The law is clear that teaching away requires more than silence; it requires an express statement regarding the unadvisable or disadvantageous nature of a given element.
(Teva’s Post-Trial Brief at 89.) This is a red herring. While it is true that the T96 Application does not teach away from unlisted
heterocycles
— ie., it does not include any teaching that pyrazoles or other heter-ocycles would
not
work — this is not the relevant test. The question is whether it would have been obvious to the person of ordinary skill that other unlisted heterocy-cles
would
work and should therefore be included in the pharmacophore.
See Syntex (U.S.A) LLC v. Apotex, Inc.,
2006 U.S. Dist. LEXIS 36089 , at *64-65 (N.D. Cal. June 2, 2006) (the question of whether a reference teaches away from a given use is separate and distinct from the question of whether there is motivation to combine the references in the asserted way). Not saying something
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Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/2310522. Public record. Not legal advice.