US Legal and Regulatory Update

Introduction

In a ¹ decision ² that continues the recent trend of Court of Appeals for the Federal Circuit (CAFC) toward stricter scrutiny of patent claims, the CAFC affirmed the Patent Trial and Appeal Board’s (PTAB) determination that all claims of Pfizer’s U.S. Patent No. 9,492,559 (“’559 patent”) challenged in five inter partes reviews (IPR) proceedings were obvious. The CAFC affirmed-in-part and vacated-in-part the PTAB’s denial of Pfizer’s motions to amend certain claims.

The invention

The ’559 patent claims immunogenic compositions comprising glycoconjugates of various Streptococcus pneumoniae serotypes for use in pneumococcal vaccines. Of the 45 claims challenged in the IPRs, three were set forth in the opinion as being representative. 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 additional two (claim 3) or four (claims 4) serotype-specific glycoconjugates:

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.

The PTAB challenge

Challengers Merck Sharp & Dohme Corp. and Sanofi Pasteur Inc. and SK Chemicals Co., Ltd. (“the IPR petitioners”) based their obviousness challenges at the PTAB on two prior art references mentioning the S. pneumoniae 22F serotype. The prior art references asserted against the claims were:

(1) US Patent Publication No. 2007/0071711 (“GSK ’711”), which discloses S. pneumoniae vaccines having capsular saccharide antigens, with saccharides derived from S. pneumoniae serotypes that may include a saccharide conjugant of 22F; and

Despite the lack of a disclosure in either prior art reference of a general range of molecular weight of the pneumoniae serotype 22F glycoconjugate, the PTAB found that one of skill in the art would have been obvious to arrive at the claimed invention through routine optimization. Pfizer also filed a motion to amend claims (discussed in more detail below), which the PTAB determined that the proposed substitute claims were unpatentable for the same reasons as the original claims. Pfizer appealed the PTAB decision.

The CAFC appeal

The basis for Pfizer’s appeal of the PTAB’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”), and because there was no overlap between a claimed and prior art range, there could have been no motivation to optimize such nonexistent range to reach the claimed range. It was undisputed that neither GSK ’711 nor Merck ’086 disclosed a molecular weight for the claimed serotype 22F conjugate.

A “results-effective variable” is a variable that is recognized by one of skill in the art as achieving a recognized result. ³ The results-effective variable doctrine is a caselaw principle wherein prior art disclosing the “general conditions of a claim” can invoke a presumption of obviousness if the claimed ranges are identifiable through routine experimentation and variation of prior art ranges.

Under the results-effective variable doctrine, an overlap between a claimed range and numerical range disclosed by the prior art creates a presumption of obviousness. This presumption can be rebutted by the patent owner with evidence that the given parameter was not recognized as results-effective.

The CAFC affirmed the PTAB rejection of this argument. In the PTAB’s viewpoint, the molecular weight at issue was a “results-effective variable” and under the doctrine thereof a skilled artisan would have been motivated to optimize the molecular weight to provide a conjugate having improved stability and good immune response. The results-effective variable 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.”

As the CAFC explained, the fact that the results-effective variable doctrine creates a presumption of obviousness when there is an overlap in claimed and prior art numerical ranges does not mean that the doctrine is applicable only when an overlap exists. The CAFC noted that optimization analyses for obviousness determinations regularly consider the motivations of a person having ordinary skill in the art to combine prior art references with the ability to bridge any gaps in the prior art while retaining a reasonable likelihood of success.

Moreover, GSK ’711 discloses both a serotype 22F glycoconjugate and the molecular weights for fourteen other S. pneumoniae serotype glycoconjugates, such molecular weights ranging from 1303 kDa to 9572 kDa, overlapping with the claimed range of 1000 kDa to 12,500 kDa. The PTAB further explained that GSK ’711 discloses that “saccharide conjugate vaccines retaining a larger size of saccharide can provide a good immune response against pneumococcal disease,” and that both GSK ’711 and Merck ’086 disclose that known methods and techniques could be used to isolate the polysaccharide from the bacteria and to couple it to a carrier protein. Both GSK ’ 711 and Merck ’086 disclose methods for preparing S. pneumoniae glycoconjugates and teach that the polysaccharides can be sized to improve the filterability of the conjugated product. Expert testimony further supported the idea that, at the time of the invention, conjugation techniques and conditions were routine such that a person of ordinary skill in the art would have understood the claimed molecular weight to be “typical of immunogenic conjugates.” Such evidence therefore was held to support the PTAB’s conclusion that “conjugate size is a results-effective variable associated with improved stability of conjugates and good immune response, limited only by filter size, thereby rendering ‘optimization within the grasp of one of ordinary skill in the art.’”

Pfizer’s second argument was that because the unpredictability of the art is high, and because the prior art lacks examples showing the key features, there would have been no reasonable expectation of success. The CAFC explained that a prior art reference “is not limited to its specific working examples,” and “the expectation of success need only be reasonable, not absolute.” Although Pfizer presented evidence to the PTAB that glycoconjugate molecular weight requires case-by-case experimentation and is thus unpredictable, the CAFC held that the alleged unpredictability was not at issue in cases, such as the present appeal, where the method of producing glycoconjugates is generally recognized as routine.

Finally, the CAFC affirmed-in-part and vacated-in-part the PTAB’s denial of Pfizer’s motions to amend certain claims.

During the IPRs, Pfizer submitted a motion to amend its claims that proposed to substitute claims 46, 48, and 49, with additions to claim 1 essentially as follows:

46. [The composition of claim 1 further comprising:] … glycoconjugates from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F all individually conjugated to CRM₁₉₇… wherein the composition exhibits more than a 2-log increase above baseline … across all serotypes in the composition …

With regard to proposed claim 46, the CAFC affirmed the PTAB’s conclusion that it would have been obvious to arrive at the claimed composition with a reasonable expectation of success. Pfizer argued that “where the prior art contains evidence directly showing that others failed to achieve the claimed invention (as here), there can be no finding of obviousness.” The CAFC disagreed that this is the case here. Although the prior art did not cover all variations, “a finding of obviousness does not require a guarantee of success.” As to proposed amended claims 48 and 49, the CAFC vacated and remanded only because the PTAB did not provide a specific “reasoned basis” for its finding “sufficient to permit meaningful judicial review.” That is, the PTAB did not specifically address proposed claims 48 and 49, but swept the PTAB’s conclusion of obviousness in with their analysis of proposed claim 46. It is reasonable to assume that the reprieve from the finding of obviousness of these claims might be short-lived, only up to the point that the PTAB explicitly addresses claims 48 and 49 on remand.

Conclusion

The CAFC reaffirmed that an expectation of success need only be reasonable, not absolute, a phrase that will certainly appear in a great many future office actions and opinions.

Such decision follows Guidelines published by the US PTO on February 27, 2024 entitled “Updated Guidance for Making a Proper Determination of Obviousness”, which clarify that US patent examiners should maintain (1) a flexible approach to understanding the scope of prior art and (2) a flexible approach to providing a reason to modify the prior art, rather than relying on rigid tests for doing so.

The results of Pfizer, especially read in light of the noted US PTO Guidelines, highlights a continued drift by the PTAB and courts toward stricter scrutiny of patent claims, both during prosecution of the claims and during later litigation of the claims. Such claims will be somewhat more difficult to procure, and more open to later invalidation during litigation.