User:BD2412/Vaccine law resources/Patent

Merck Sharp & Dohme Corp. v. Wyeth LLC (Fed. Cir. 2019)

The '999 patent, owned by Wyeth LLC ("Wyeth"), is directed to formulations for stabilizing polysaccharide-protein conjugate vaccines. These vaccines are derived from the capsular polysaccharides present on the surface of certain disease-causing bacteria. The human immune system can use these capsular polysaccharides to detect and identify different serotypes (i.e., strains) of a species of bacteria. Polysaccharide vaccines can be monovalent (comprising a single serotype), or multivalent (comprising multiple serotypes). For example, a 13-valent vaccine would contain polysaccharides from 13 different serotypes. Because these polysaccharides typically have low immunogenicity (i.e., ability to provoke an immune response), it is desirable to enhance the effectiveness of these vaccines by conjugating (i.e., bonding) the polysaccharides to a carrier protein with high immunogenicity. However, as the '999 patent explains, polysaccharide-protein conjugate vaccines aggregate (i.e., clump together) when exposed to silicone oil, a common lubricant used in vaccine storage containers. The invention described in the '999 patent is a formulation that inhibits silicone-induced aggregation by suspending the polysaccharide-protein conjugate in a mixture of (1) a pH-buffered saline solution and (2) an aluminum salt.

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... the Board found all the challenged claims except one—claim 18—to be unpatentable as obvious. Claim 18 covers a 13-valent pneumococcal conjugate vaccine. In both proceedings, the Board rejected Merck's argument that the formulation recited by claim 18 was obvious in light of the prior art. Merck appeals the Board's decisions as to claim 18.

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The Board found that although Peña disclosed a "13-valent pneumococcal conjugate vaccine with the same serotypes recited by claim 18 that is described as being in an 'advanced phase of study,'" Merck failed to "direct [the Board] to any disclosure in Peña, or other evidence of record, further characterizing the vaccine or the study." J.A. 44 (citing J.A. 272, 992), see also J.A. 86. The Board stated that it was "unable to assess whether the study involved a formulation comprising each of the thirteen known serotypes conjugated to a CRM197 polypeptide, [the carrier protein] required by the claim, or if such an attempt was even considered, tried, and successful." Id. The Board concluded that Merck "ha[d] not provided a reason that a person of skill in the art would have modified Chiron's formulation to comprise a thirteen valent conjugate," and that "[Merck] ha[d] not provided sufficient evidence for [the Board] to determine whether a skilled artisan who endeavored to modify Chiron's formulation to yield a 13-valent pneumococcal conjugate vaccine with the same serotypes as in Peña would have had a reasonable expectation of successfully doing so." Id. at 44. Merck Sharp & Dohme Corp. v. Wyeth LLC (Fed. Cir. 2019)

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The parties' differences primarily concerned whether a skilled artisan would have been dissuaded from using a single carrier protein (i.e. CRM197) due to "immune interference," a phenomenon that may result in decreased immunogenicity in multivalent vaccines with a sole carrier protein. Merck argues that the immune interference issue is irrelevant, quoting the Board's claim construction of the term "polysaccharide-protein conjugate[]" as not requiring "any specific level of immunogenicity for the composition."

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J.A. 10. However, this issue is relevant to whether a skilled artisan would have been motivated to conjugate the 13 serotypes with CRM197 as a sole carrier protein. "If all elements of a claim are found in the prior art, as is the case here, the factfinder must further consider the factual questions of whether a person of ordinary skill in the art would be motivated to combine those references . . . ." Dome Patent L.P. v. Lee, 799 F.3d 1372, 1380 (Fed. Cir. 2015); see also KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) ("[I]t can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does.").

        On the issue of immune interference, Wyeth's expert testified that "[a] [person of ordinary skill in the art] would have had significant concerns expanding the formulation of [the 7-valent] Prevenar [prior art reference] because of the possible loss of immunogenicity due to 'immune interference' when developing a 13-valent conjugate vaccine," and that "[v]accine development researchers believed that mixed-carrier [i.e., multiple different] conjugates provided the most reasonable technical solution for increasing the number of polysaccharide serotypes in a multivalent conjugate vaccine." J.A. 6090-91. On the other hand, Merck's expert testified that he "strongly disagree[d]" with the assertion that "concerns over 'immune interference' would have dissuaded a [person having ordinary skill in the art] from pursuing a 13-valent formulation in which each polysaccharide is conjugated to [only] CRM197." J.A. 699.

        Despite these clearly disputed factual issues, the Board simply did not address the evidence as to whether someone skilled in the art would have been motivated to combine the 13 serotypes into a CRM197 conjugate or whether the potential loss of immunogenicity would have dissuaded someone skilled in the art from making such a combination. The fact that Peña did not disclose such a combination fails to answer this central question, and an

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explanation was particularly necessary given the Board's finding that the use of CRM197 was obvious with the 7-valent conjugate in claim 17—which also uses CRM197 as a sole carrier protein. We conclude that the Board's decision is too cryptic to survive judicial review.

New biosimilar transparency law

• Jarrod Voss, Purple is the new orange: new law in the US provides greater transparency for biosimilar applicants (3 March, 2021): Dec. 2020 law requires public disclosure of previously confidential list of patents for which "claim of patent infringement could reasonably be asserted".

Allele v. Pfizer

• Reuters, Regeneron, Pfizer sued for patent infringement over COVID antibody cocktail, vaccine (October 5, 2020)
  • San Diego biotech company Allele Biotechnology and Pharmaceuticals Inc. sued Regeneron Pharmaceuticals Inc and Pfizer Inc, "accusing them of infringing a patent on a fluorescent protein" in the course of developing COVID antibodies and vaccines.