Last week, the Federal Circuit handed down its opinion in Pfizer Inc. v. Sanofi Pasteur Inc., affirming the Patent Trial and Appeal Board's (PTAB) determination that all claims of U.S. Patent No. 9,492,559 challenged in five inter partes review (IPR) proceedings were obvious. In light of the Office's promulgation of Guidance to the examining corps as well as PTAB judges of the "increased flexibility" in obviousness determinations mandated by the Supreme Court's decision in KSR v. Teleflex and the Federal Circuit's application of that mandate since the Court's decision, the instant decision (by both the PTAB and the Court) is informative if not necessarily illustrative.
The claims of the '559 patent are directed to "immunogenic compositions" (used in vaccines) against Streptococcus pneumoniae capsular saccharide antigens. Of the 45 claims challenged in these IPRs three were set forth in the opinion as being representative:
1. An immunogenic composition comprising a Streptococcus pneumoniae serotype 22F glycoconjugate, wherein the glycoconjugate has a molecular weight of between 1000 kDa and 12,500 kDa and comprises an isolated capsular polysaccharide from S. pneumoniae serotype 22F and a carrier protein, and wherein a ratio (w/w) of the polysaccharide to the carrier protein is between 0.4 and 2.
3. The immunogenic composition of claim 1, wherein the composition further comprises a S. pneumoniae serotype 15B glycoconjugate and a S. pneumoniae serotype 33F glycoconjugate.
4. The immunogenic composition of claim 3, wherein the composition further comprises a S. pneumoniae serotype 12F glycoconjugate, a S. pneumoniae serotype 10A glycoconjugate, a S. pneumoniae serotype 11A glycoconjugate and a S. pneumoniae serotype 8 glycoconjugate.
Claim 1 recites the claimed compositions most broadly (directed to the serotype 22F glycoconjugate having a range of specific molecular weights) and the two dependent claims recite in addition combinations of two (claim 3) or 4 (claims 4) additional serotype-specific glycoconjugates. Challengers Merck Sharp & Dohme Corp. and Sanofi Pasteur Inc. and SK Chemicals Co., Ltd. based their obviousness challenges on a combination of prior art: PCT Patent Application Publication No. 2007/071711 ("GSK-711") and U.S. Patent Application Publication No. 2011/0195086 ("Merck-086"), wherein the opinion notes that GSK-711 was directed to vaccines against S. pneumoniae comprising "'capsular saccharide antigens (preferably conjugated), wherein the saccharides are derived from at least ten serotypes of S. pneumoniae,' which may include an 'S. pneumoniae saccharide conjugate of 22F,'" while Merck-086 disclosed "'multivalent immunogenic composition[s] having 15 distinct polysaccharide-protein conjugates' in which an S. pneumoniae serotype, including 22F, is conjugated to a carrier protein."
In addition to these obviousness determinations, the Board denied Pfizer's contingent motions to amend (as not proposing patentable substitute claims). This appeal also followed a denial by the Director of Pfizer's request for Director Review on remand from the Federal Circuit's earlier decision in the wake of United States v. Arthrex, Inc.
The Federal Circuit affirmed the Board's finding that claims 1-45 of the '559 patent were obvious and denial of some (as to claims 46, 47, and 50-52) but not others (claims 48 and 49) of Pfizer's proposed substitute claims, remanding with regard to these claims. The basis for Pfizer's appeal of the Board's obviousness determination was that neither cited reference disclosed the range recited in independent claim 1 ("wherein the glycoconjugate has a molecular weight of between 1000 kDa and 12,500 kDa"). The panel rejected this argument, applying the rubric from OSI Pharms., LLC v. Apotex Inc., 939 F.3d 1375, 1382 (Fed. Cir. 2019) (quoting Regents of Univ. of Cal. v. Broad Inst., Inc., 903 F.3d 1286, 1291 (Fed. Cir. 2018)) that "[a]n obviousness determination requires finding that a person of ordinary skill in the art would have been motivated to combine or modify the teachings in the prior art and would have had a reasonable expectation of success in doing so." In the Board's view (agreed to by the Federal Circuit), the limitation at issue was a "result-effective variable" and under the "result effective variable doctrine" the skilled artisan "would have been motivated to optimize to provide a conjugate having improved stability and good immune response," based on inter alia E.I. DuPont de Nemours & Co. v. Synvina C.V. This doctrine depends on the "common sense" of the skilled worker, who would have been motivated not by any specific prior art teaching but generally to "discover the optimum or workable ranges by routine experimentation" (a concept at the heart of the Supreme Court's KSR decision and embodied in the recent Office Guidance, that the person of ordinary skill in the art is not "an automaton"). While typically arising in cases where a claimed numerical range overlaps with a prior art range (see, Genentech, Inc. v. Hospira, Inc.) the opinion asserts that the result-effective variable doctrine is not limited to such instances, and the Court held that the Board was correct in determining whether this variable range, while not expressly recited in the cited prior art, would be a parameter that the skilled worker would be motivated to optimize. In addition, the opinion notes that the cited references disclosed the molecular weights of the expressly recited 22F serotype as well as 14 other S. pneumoniae serotypes in support of the Board's conclusion (thereby also inherently providing an overlapping molecular weight range for these serotypes and the benefits thereof). Nor was there anything unknown in the prior art regarding conjugation methods or carrier protein-conjugated polysaccharide antigens according to the opinion, and Pfizer's contrary evidence that whether such conjugates were unexpected must be determined on a case-by-case basis was not persuasive to the panel. Being dependent on the existence of substantial evidence the Court held that the Board's application of this reasoning for determining that the claims were obvious was not in error and affirmed.
Turning to dependent claims 3 and 4 the Federal Circuit rejected Pfizer's argument (considered and rejected by the Board) that the factual evidence was insufficient to support an obviousness determination because the prior art did not exemplify competence of the other recited carrier protein-conjugated polysaccharide antigens as immunogenic compositions. Unpredictability, according to the opinion, is not the standard because "the expectation of success need only be reasonable, not absolute," citing Pfizer, Inc. v. Apotex, Inc. (emphasis in opinion). In addition, these specific polysaccharide antigens (in forms not conjugated to proteins) were known to be immunogenic in the prior art (for example, being encompassed as part of commercially available pneumococcal vaccines such as PNEUMOVAX®). This reasoning and expert testimony was persuasive to the Board and to the panel that "the person of ordinary skill in the art would have reasonably expected that the claimed glycoconjugates could be incorporated into a vaccine 'while maintaining the immunogenicity to all serotypes in the composition.'"
The opinion considers the Board's denial of Pfizer's motions to amend (to substitute claims for the challenged claims) under the Administrative Procedures Act standard of whether this decision was "arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law," citing 5 U.S.C. § 706(2)(A). The opinion sets forth proposed substitute claims 46, 48 and 49 in this regard:
46. An immunogenic composition comprising:
a Streptococcus pneumoniae serotype 22F glycoconjugate, wherein the 22F glycoconjugate has a molecular weight of between 1000 kDa and 12,500 kDa and comprises an isolated capsular polysaccharide from S. pneumoniae serotype 22F and a CRM197 carrier protein, and wherein a ratio (w/w) of the polysaccharide to the carrier protein is between 0.4 and 2;
glycoconjugates from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F all individually conjugated to CRM197;
an aluminum salt adjuvant; and
wherein the composition exhibits more than a 2-log increase above baseline in serum IgG levels in New Zealand White Rabbits across all serotypes in the composition following administration of two equal doses of the composition in the form of an initial dose and a booster dose.
48. The immunogenic composition of claim 1 46, wherein the composition further comprises a S. pneumoniae serotype 15B glycoconjugate and a S. pneumoniae serotype 33F glycoconjugate, wherein said serotypes 15B and 33F are all individually conjugated to CRM197.
49. The immunogenic composition of claim 3 48, wherein the composition further comprises a S. pneumoniae serotype 12F glycoconjugate, a S. pneumoniae serotype 10A glycoconjugate, a S. pneumoniae serotype 11A glycoconjugate and a S. pneumoniae serotype 8 glycoconjugate, wherein said serotypes 12F, 10A, 11A and 8 are all individually conjugated to CRM197.
(Where additions underlined and deletions struck through.)
The Federal Circuit affirmed that proposed claim 46 would have been obvious in light of the cited prior art (including U.S. Patent Publication No. 2012/0237542) and "the knowledge of a person of ordinary skill in the art." The specific teachings of the art (being found in the '542 application) included (the same) thirteen serotypes recited in the proposed claims, combined with the teachings of GSK-711 and Merck-086 regarding the 22F serotype in support of obviousness. The panel responds to Pfizer's assertion that the combination of the art did not disclose successful production of an immunogenic composition having a 2-log increase in serum IgG by reciting the aphorism that "an expectation of success need only be reasonable, not absolute" from Pfizer, Inc. v. Apotex, Inc. (emphasis in opinion), because here, according to the opinion, the cited art "clearly demonstrated that the claimed 2-log IgG increase could be achieved across various serotypes in a multivalent compositions." For claim 46, the panel agreed that the Board's denial of Pfizer's motion to amend was supported by substantial evidence.
Not so for claims 48 and 49, however. The difference for these claims is the limitation that the greater than 2-log increase must be exhibited "across all serotypes within the claimed composition" (emphasis in opinion). The panel found no explanation in the record for why the Board came to the same conclusion regarding obviousness for these claims that it had for claim 46, and "it is hornbook law" that an administrative agency "must provide a 'reasoned basis' for their actions that is sufficient to permit meaningful judicial review." See In re Theripion. On this basis the Federal Circuit remanded for further consideration by the Board.
Finally, the Federal Circuit affirmed the Director's decision not to review the Board's decision in the face of Pfizer's argument that the entire Director Review procedure violates the APA for not being "promulgated through notice-and-comment rulemaking" because the Office has changed its webpage "multiple times since it was created." In earlier cases, the Court had held that this argument could be successfully made only if an appellant showed "prejudicial error," which Pfizer did not do here according to the opinion.
Pfizer Inc. v. Sanofi Pasteur Inc. (Fed. Cir. 2024)
Panel: Circuit Judges Lourie, Bryson, and Stark
Opinion by Circuit Judge Lourie
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