03/28/14

Pfizer v. Teva: Claimed Compound Not Limited to Racemic Mixture Thereof

Category: Infringement   
 
 
 
 By: Eric Paul Smith, Contributor  
 
TitlePfizer Inc. v. Teva Pharmaceuticals USA, Inc., Nos. 2012-1576, -1601, -1602, -1603, -1604, -1605, -1607 (Fed. Cir. Feb. 6, 2014) (non-precedential).
Issues"Appellants[] appeal from a final judgment . . . that found various claims of the asserted patents infringed and from the court's holdings regarding enablement, written description, and obviousness." Pfizer at *4 (citations omitted). "Due to its scope and the breadth of the injunction entered, the disposition of this appeal rests entirely on a single claim: claim 2 of [U.S. Patent No. 6,197,819 (the ']'819 patent[')]." Id. at *5. At issue are (1) whether "the district court [correctly] construed the term '4-amino-3-(2-methylpropyl) butanoic acid' to mean 'the chemical compound 4-amino-3-(2-methylpropyl) butanoic acid,' without limitationas to stereochemical form," Pfizer at *6; and (2) whether "claim 2 is not invalid for lack of [a] enablement, [b] insufficient written description, or [c] obviousness," Id. at *7.
Holdings
(1) "We perceive no error in the district court's construction. . . . The patent specification discusses 4-amino-3-(2-methylpropyl) butanoic acid [hereinafter 3-isobutylGABA] as the 'preferred compound' generally and without regard to its stereochemistry. The specification makes clear that the patentee expressly used the word 'racemate,' 'racemic,' or its standard prefix (R, S) to refer to the chiral compound's racemate. Likewise, the patentee used standard prefixes (R) or (S) to designate a particular enantiomer of the compound. Because the patentee included no such references or prefixes in claim 2, it should not be so limited." Pfizer at *9 (citations omitted).
(2)(a) "In view of the finding that enantiomer separation methods are well-known and routine to a person of ordinary skill, we agree with the district court that the inventors were not required to provide a detailed recipe for preparing every conceivable permutation of the compound the invented to be entitled to a claim covering that compound. . . . [C]laim 2 satisfies the requirements under § 112(a) because the '692 application's disclosure, coupled with the methods for synthesis and resolution that were found to be well-known and routine in the art, is sufficiently enabling." Id. at *12 (citations omitted).
(2)(b) "[W]ritten description does not require inventors . . . to reduce to practice and be in physical possession of every species . . . of a genus . . . claim. [A]n application satisfies the written description requirement when it details 'relevant identifying characteristics' such that the compound can be distinguished from other compounds. Here, the '692 application not only disclosed the structure of 3-isobutylGABA as the preferred embodiment of the invention, but also set forth in vitro and in vivo data for the compound, and described a method of synthesizing the compound. [S]uch a description is sufficient for persons of ordinary skill in the art to recognize that the inventor invented what is claimed." Id. at *14 (citations omitted).
(2)(c) "The district court did not err in finding that Appellants failed to establish that gabapentin or 3-isopropylGABA would have been selected as lead compounds, or that Appellants failed to set forth evidence identifying the necessary teachings for a skilled artisan to modify alkyl groups at GABA's 3-position to improve anticonvulsant activity. Because we agree with the district court that the Appellants failed to prove that claim 2 would have been prima facie obvious over the asserted prior art compounds, we need not address the court's findings regarding secondary considerations of nonobviousness." Id. at *20 (citations omitted).
 
 

Procedural History"Defendants-Appellants Teva Pharmaceuticals USA, Inc.; Teva Pharmaceutical Industries, Ltd.; Lupin, Ltd.; Lupin Pharmaceuticals, Inc.; Actavis, Inc.; Actavis Elizabeth, LLC; Cobalt Laboratories, Inc.; Cobalt Pharmaceuticals, Inc.; Sun Pharma Global, Inc; Sun Pharmaceutical Industries, Ltd.; Sun Pharmaceutical Industries, Inc.; Wockhardt Ltd.; and Mylan Pharmaceuticals, Inc. (collectively, 'Appellants') appeal from a final judgment of the United States District Court for the District of Delaware that found various claims of the asserted patents infringed and from the court's holdings regarding enablement, written description, and obviousness." Pfizer at *4.
 
 
 
Legal Reasoning (Prost, Moore, Rader, CJ)
Claim Construction and Infringement
Legal Standard"Claim construction is an issue of law that we review de novo. In construing a claim term, we look at the term's plain and ordinary meaning as understood by a person of ordinary skill in the art. There are two exceptions to this general rule: (1) when a patentee sets out a definition and acts as her own lexicographer, or (2) when the patentee disavows the full scope of a claim term either in the specification or during prosecution." Pfizer at *8 (citations omitted).
Appellants' Arguments"[Appellants] contend that the proper construction of claim 2 is that it covers only racemic (i.e., a 50:50 mixture of S- and R-enantiomers of) 3-isobutylGABA. Appellants contend that the patent specification, prosecution history, and applicant declarations submitted to the U.S. Patent and Trademark Office ('PTO') support a narrower construction of the claimed compound as a racemic mixture." Id. at *8.
Appellees' Arguments"[A] narrower construction would ignore the plain, clear, and specific language of the claim, which places no limitation on the claimed chiral compound. Appellees submit that the patentee’s inclusion of test results of the compound’s racemate in the specification, juxtaposed with the lack of a racemic limitation in the claim language, demonstrates the patentee’s intent not to limit the compound being claimed to its racemate. Appellees also point out that at trial, Appellants’ own expert admitted that claim 2 covers 3-isobutylGABA in any isomeric form, that is, the form is not defined." Id. at *8-9 (citations and internal quotation marks omitted).
Disclosure of Limited Test Results Does Not Limit Claimed Compound"The plain language of the claim does not include the narrowing limitation that the Appellants desire. The patent specification discusses 4-amino-3-(2-methylpropyl) butanoic acid as the preferred compound generally and without regard to its stereochemistry. The specification makes clear that the patentee expressly used the word 'racemate,' 'racemic,' or its standard prefix (R, S) to refer to the chiral compound’s racemate. Likewise, the patentee used standard prefixes (R) or (S) to designate a particular enantiomer of the compound. Because the patentee included no such references or prefixes in claim 2, it should not be so limited." Pfizer at *9. "Appellants also note that Tables 1 and 2 in the specification report test results pertaining only to the compound’s racemate, but not other mixtures with differing enantiomeric compositions. . . . [However, a]bsent a clear disavowal or lexicographic definition in the specification or the prosecution history, the reporting of test results limited to a racemate does not warrant importing a racemic limitation into claim 2. . . . There is no basis elsewhere in the intrinsic record to support Appellants' suggestion that the absence of an (R) or (S) prefix in claim 2 specifically signals the racemate . . . ." Id. at *9-10 (citations omitted).
Infringement"Because claim 2 was correctly construed to include 3-isobutylGABA regardless of its enantiomeric forms and infringement was stipulated to by the Appellants under this construction, we also affirm the finding of infringement." Id. at *10.
Enablement
Legal Standard"To be enabling under 35 U.S.C. § 112(a), a patent’s specification must describe the invention and the manner and process of making and using it, in such full, clear, concise, and exact terms, as to allow any person skilled in the art 'to make and use the full scope of the claimed invention without undue experimentation.' MagSil Corp. v. Hitachi Global Storage Techs., Inc., 687 F.3d 1377, 1380 (Fed. Cir. 2012) (internal quotation marks omitted)." Pfizer at *10.
Appellants' Arguments"Appellants contend that because claim 2 was construed to cover all compositions of 3-isobutylGABA, without limitation as to isomeric form, to be sufficiently enabling the ’692 application must teach a skilled artisan how to prepare every conceivable mixture of 3-isobutylGABA’s enantiomers." Id. at *11.
Enantiomer Separation Well-Known in the Art"First, there is no requirement that a specification must disclose what is routine and well known in the art. Second, as the district court found, there is no dispute in the record that the co-inventors of the ’819 patent were the first to create and claim the chemical compound 3-isobutylGABA. It is also undisputed that the parent application discloses the method for synthesizing the compound and states that the compound’s enantiomers may be prepared or isolated by methods already well known in the art." Id. at *11-12 (citations and internal quotation marks omitted). "Where a claim has been construed to cover a chemical compound, the specification is not deficient merely because it does not disclose how to prepare a particular form or mixture—among hundreds of possible permutations—of that compound. See In re Hogan, 559 F.2d 595, 606 (CCPA 1977) (noting that requiring such specific disclosures would 'impose an impossible burden on inventors'). . . . [C]laim 2 satisfies the requirements under § 112(a) because the ’692 application’s disclosure, coupled with the methods for synthesis and resolution that were found to be well-known and routine in the art, is sufficiently enabling." Id. at *12.
Written Description
Legal Standard"A party alleging that a patent is invalid for lack of written description has the burden of establishing by clear and convincing evidence that a patent disclosure does not reasonably convey to a skilled artisan that the inventor was in possession of the claimed invention at the time of the patent application." Pfizer at *13.
Appellants' Arguments"First, Sun argues that although the ’692 application discloses a chemical synthesis method for the racemate of 3-isobutylGABA, it discloses nothing towards the isolation of the enantiomers, even though claim 2 of the ’819 patent has been construed to encompass all forms of the compound. Second, according to Sun, despite the patentee describing the separation of the racemate (i.e., isolation of the enantiomers) as anything but routine in later applications, at the time of the ’692 application, both inventors readily admitted that they had not yet separated the racemic mixture to obtain a purified enantiomer." Id. at *13-14 (citations omitted).
No Requirement to Reduce to Practice or Be in Physical Possession of All Species"Sun conflates the disclosure requirement for claim 2 with that for claim 1: it argues that because the inventors had not sufficiently described the narrower claim 1 (to prebagalin) they could not have sufficiently described the broader claim 2 (to 3-isobutylGABA). . . . [W]ritten description does not require inventors, at the time of their application for a patent, to reduce to practice and be in physical possession of every species . . . claim. For claims to a chemical compound, an application satisfies the written description requirement when it details relevant identifying characteristics such that the compound can be distinguished from other compounds. Here, the ’692 application not only disclosed the structure of 3-isobutylGABA as the preferred embodiment of the invention, but also set forth in vitro and in vivo data for the compound, and described a method of synthesizing the compound. . . . [S]uch a description is sufficient for persons of ordinary skill in the art to recognize that the inventor invented what is claimed." Id. at *14 (citations omitted).
Obviousness
Legal Standard for Compounds"Whether a new chemical compound would have been prima facie obvious over particular prior art compounds follows a two-part inquiry under our precedent. First, the court determines whether a chemist of ordinary skill in the art would have selected the asserted prior art compound as a lead compound, or starting point, for further development. A lead compound is a compound in the prior art that would be most promising to modify in order to improve upon its activity and obtain a compound with better activity. The selection analysis may be guided by evidence of the compound’s pertinent properties, such as chemical activity or potency. Mere structural similarity between a prior art compound and the claimed compound does not inform the lead compound selection." Pfizer at *17 (citations and internal quotation marks omitted). "The second step of the obviousness analysis requires a showing that the prior art would have taught a skilled artisan to make specific molecular modifications to a lead compound so that the claimed compound may be made with a reasonable expectation of success." Id. at *19 (citations and internal quotiation marks omitted).
Appellants' Arguments"Appellants contend on appeal that the district court clearly erred in failing to make the following findings: (1) Fish, Shashoua, and Colonge taught that 3-isopropylGABA and other homologous compounds may have anticonvulsant activity; (2) one of ordinary skill in the art would have expected 3-isobutylGABA to have anticonvulsant activity due to its structural similarities to 3-isopropylGABA; and (3) gabapentin, a 3-alkylGABA compound in the prior art with demonstrated anticonvulsant efficacy, provided a motivation for persons skilled in the art to try other alkyl substituents at GABA’s 3-position." Id. at *16.
Evidence for Selection of Lead Compound Too Sparse"With respect to gabapentin, no evidence in the record firmly situates gabapentin in the prior art or otherwise supports its selection as a lead compound. At most, Appellants established that gabapentin was being tested for its anticonvulsant effect contemporaneously with 3-isobutylGABA, but there is no testimony establishing its being tested prior to the discovery of 3-isobutylGABA." Id. at *17-18 (citations omitted). "Record evidence supporting 3-isopropylGABA’s candidacy as a lead compound is just as meager. . . . [N]othing in the Fish, Shashoua, and Colonge references single out 3-isopropylGABA, among the other compounds within the references’ broad disclosures, as a promising compound to modify due to its anticonvulsant effect. In addition, these references fail to identify a lead compound because they disclose nothing concrete about 3-isopropylGABA or its mechanisms of action, including whether it has anticonvulsive properties." Id. at *18-19.
Evidence for Motivation to Modify Too SparseWith respect to gabapentin, "there is no evidence in the record of motivation for a skilled artisan to modify gabapentin for further anticonvulsant research. Appellants chose to emphasize that gabapentin was a solid choice for a skilled artisan based on its structural similarity to pregabalin, a fact the specification of the ’819 patent acknowledged. A patent challenger, however, must demonstrate the selection of a lead compound based on its promising useful properties, not a hindsight-driven search for structurally similar compounds." Id. at *18 (citations and internal quotation marks omitted). With respect to 3-isobutylGABA, "the record also supports the district court’s finding that Appellants failed to identify the teachings required in the second step of the inquiry. According to Appellants, the disclosures in Fish, Shashoua, and Colonge would have taught a skilled artisan to modify lower alkyl substitutes—which includes isobutyl—at GABA’s 3-position to achieve 3-isobutylGABA. However, it is quite evident that the Fish, Shashoua, and Colonge references together disclosed trillions of compounds without calling out alkyl groups in particular or singling out isobutyl specifically. . . . [T]he Appellants did not point to any evidence in the prior art indicating that a particular compound or class of compounds nor identify any teachings as of the filing date that would have directed a skilled artisan to substitute [at GABA’s 3-position] with an isobutyl group, as opposed to any other alkyl group.” Indeed, a vague suggestion in the prior art pointing to a broad class of compounds, without any teaching particularly identifying isobutyl among the millions of potential compounds, is not a teaching of specific molecular modifications required by our precedent. [Additionally,] Appellees . . . credibly established that anticonvulsant drug discovery in 1990 was complicated, unpredictable, and largely conducted through trial and error. This finding would have precluded any argument . . . that there would have been a reasonable expectation of success to achieve an anticonvulsant in 3-isobutylGABA . . . ." Id. at *19-20 (citations and internal quotation marks omitted).
Conclusion
Claim 2 Was Properly Construed, Is Valid, and Was Infringed"We hold that the district court did not err in its conclusion that claim 2 of the ’819 patent has been infringed, and that Appellants failed to prove that the claim is not enabled, insufficiently described, or obvious. . . . Accordingly, we affirm the district court’s judgments of infringement and no invalidity." Pfizer at *21.
 
 
Image Attribution Statement: Ben Mills, “Ball-and-stick model of an enantiomeric pair of mecoprop molecules, as found in the crystal structure of racemic mecoprop. The (S)-(−)-enantiomer is on the left; the (R)-(+) enantiomer is to the right,” public domain, see http://en.wikipedia.org/wiki/File:Mecoprop-racemic-dimer-from-xtal-labelled-3D-balls.png (last visited March 29, 2014).
 
 
 
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