Case Name: Wyeth Holdings Corp. v. Sandoz, Inc., Civ. No. 09-955-RGA-CJB, 2012 U.S. Dist. LEXIS 76998 (D. Del. Apr. 5, 2012) (Burke, M.J.)
Drug Product and Patent(s)-in-Suit: Tygacil® (tigecycline); U.S. Pat. Nos. 7,879,828 ("the '828 patent") and RE40,183 ("the '183 patent").
Nature of the Case and Issue(s) Presented: The issue here concerns whether the '828 was invalid as obvious under the doctrine of non-statutory double patenting. Plaintiff Wyeth's '183 patent issued in March 2008, was a reissue of U.S. Pat. No. 5,494,903 ("the '903 patent") and claims the chemical compound "7-Substituted-9-Substituted Amino-6-Demythyl-6-DeoxyTetracyclines." The patent is directed generally to tetracycline derivatives with antibacterial properties. Claim 97 of the '183 patent also claims a "pharmaceutical composition of matter" that includes a tetracycline "compound" as well as a "pharmaceutically acceptable carrier." In February 2011, the '828 patent issued. The '828 patent, entitled "Tigecycline Compositions and Methods of Preparation," claims compositions that include tigecycline, lactose, and an acid. Tigecycline is a particularly effective intravenous treatment against certain strains of drug-resistant bacteria and is marketed under the brand name Tygacil®.
In the instant case, Wyeth asserted that defendant Sandoz, Inc. ("Sandoz") infringed the '828 and '183 patents when it filed an ANDA seeking permission to manufacture a generic injectable form of tigecycline. Sandoz stipulated that its submission of the ANDA and subsequent manufacture, use, and sale of generic tigecycline would infringe the claims of the patents-in-suit if they were valid and enforceable. Sandoz challenged the validity of both patents-in-suit, and on February 10, 2012, moved for partial summary judgment pursuant to the doctrine of obviousness-type double patenting, arguing that claim 97 of the '183 patent rendered the asserted claims of the '828 patent invalid. The court held that summary judgment was improper because Sandoz failed to establish by clear and convincing evidence that the claims at issue are not patentably distinct.
Why Wyeth Prevailed: When Wyeth filed the '828 patent application in March 2006, it was initially rejected as obvious over the applicant's submission of prior art in combination with another U.S. Patent application known as "Testa." The Examiner concluded that it would have been prima facie obvious for a person of ordinary skill in the art to lyophilize the composition before adding an acid to lower pH and combat oxidation. In response, Wyeth argued that while Testa referred to lactose as one of a number of possible excipients, it did not teach lactose as a stabilizer, and ultimately persuaded the Examiner to withdraw his rejection and conclude that the claimed composition unexpectedly reduces epimerization and stabilizes the tigecycline. The '828 patent application referenced the '903 patent as prior art, but the Examiner never rejected the application on the basis of statutory or non-statutory double-patenting.
The Court first construed the relevant claim terms, specifically determining what constituted a "compound according to claim 1 [of the '183 patent]" and a "pharmaceutically acceptable carrier." The Court construed "compound" to mean "a tetracycline derivative of the formulae set forth in claim 1, including but not limited to tigecycline" and "pharmaceutically acceptable carrier" to mean "any solid or liquid, including but not limited to lactose, that may be combined with a tetracycline derivative of the formulae set forth in claim 1, and that results in an antibacterial formation." Having considered the meaning of the claim terms, the Court employed a two-step analysis of obviousness-type double-patenting. First, the Court identified five key differences between the claims: (i) the '183 patent referred to a broad range of tetracycline derivatives, while the '828 patent referred only to tigecycline; (ii) the '183 patent referred to a broad range of pharmaceutically acceptable carriers, while the '828 patent referred only to lactose; (iii) the '828 patent identified hydrochloric and/or gentisic acids as part of the composition, while the '183 patent included no reference to an acidic element; (iv) the '828 patent specified particular molar ratios of tigecycline to lactose, while the '183 patent contained no ratio; and (v) the '828 patent specified that the composition must be acidic within the pH range of 3.0 and 7.0, while the '183 patent contained no pH range.
Next, the court addressed whether the differences rendered the claims patentably distinct. Sandoz argued first that the two elements of the '828 patent's composition (tigecycline and lactose) fell within the scope of the broader claims of claim 97 of the '183 patent, and second that the remaining elements of the '828 patent claims were insignificant and obvious modifications to claim 97 of the '183 patent. The Court found that where the '183 patent claimed a large "genus" of tetracycline derivatives and pharmaceutical carriers, the '828 patent claimed a narrow "species" of tetracycline derivatives (tigecycline) and pharmaceutically acceptable carriers (lactose). The Court relied on established precedent that did not preclude a later patent from claiming a species within a previously claimed genus, so long as the species is novel, useful, and non-obvious. Next, the Court addressed Sandoz's second claim that there were no patentable distinctions between the '183 patent and the remaining elements of the '828 patent's claims, specifically the molar ratios of tigecycline to lactose, pH levels, and the inclusion of particular acids. Sandoz claimed that the molar ratio of tigecycline to lactose was "an arbitrary range" and did not render the claims in the '828 patent patentably distinct from the '183 patent. The Court disagreed and found that Sandoz did not offer sufficient evidence to contradict Wyeth's evidence asserting that the molar ratios were key to simultaneously stabilizing the rate of oxidation and epimerization. Next, Sandoz claimed that because the '183 patent disclosed a broadly defined mixture of a compound (which could be tigecycline) and a carrier (which could be lactose), and because the more specific mixture disclosed by the '828 patent fell within those more expansive parameters, the claims-at-issue in the '828 patent were not patentable. The Court again held that the genus-species distinction does not automatically foreclose patentability, and while Sandoz could ultimately present evidence that the claimed molar ratios were obvious, it had not met the burden of proof at the summary judgment stage. Similarly, the Court held that Sandoz did not offer sufficient evidence to support its claim that the pH ranges in the '828 patent had no apparent significance, or its claim that using hydrochloric acid to reduce the pH of the composition would have been obvious in view of the broad pH range claimed in the '183 patent.
The court also considered whether evidence of secondary considerations of nonobviousness can be considered when evaluating non-statutory double patenting. In Geneva v. GlaxoSmithKline, 349 F.3d 1373, 1378 n.1, the Federal Circuit commented on differences between a Section 103 obviousness analysis and an obviousness-type double-patenting inquiry, and noted, among other things, that "[o]bviousness requires inquiry into objective criteria suggesting non-obviousness; non-statutory double patenting does not." Based on Geneva, Sandoz argued that secondary considerations should not be part of the analysis. The district court noted conflicting opinions among the judges in Delaware, and ultimately held that Geneva does not foreclose consideration of secondary indicia of nonobviousness as part of the non-statutory double patenting inquiry.
Although it did not have the burden of proof of Sandoz's summary-judgment motion, Wyeth identified evidence supporting the claim that the combination of lactose, tigecycline, and acid in the '828 patent was not self-evident or obvious in light of the '183 patent or other prior art. Because the Court was required to draw all reasonable inferences in favor of the non-moving party, Wyeth's evidence of an "unexpected antibacterial synergy" made summary judgment improper. The Court held that, while Sandoz may ultimately be able to demonstrate that the "allegedly ‘unconventional'" choice of lactose in combination with acidic conditions was the result of the application of conventional and obvious principles, it had not demonstrated through clear and convincing evidence that the ‘828 patent impermissibly extended the term of the '183 patent.
