Wyeth Unable to Vaccinate Itself Against Federal Circuit Remand

Decision: Merck Sharp & Dohme Corp. v. Wyeth LLC, --F.3d__ (Fed. Cir. Nov. 26, 2019) (non-precedential) (DYK, Prost, Wallach)

Holding: The PTAB’s decision declining to find claim 18 of Wyeth’s involved patent obvious was insufficiently supported, and therefore the Court vacated and remanded.

Background: Wyeth’s patent, U.S. 8,562,999, is directed to formulations for stabilizing and inhibiting precipitation of polysaccharide-protein conjugate vaccines. Independent claim 1 reads:

1. A formulation comprising
(i) a pH buffered saline solution, wherein the buffer has a pKa of about 3.5 to about 7.5,
(ii) an aluminum salt and
(iii) one or more polysaccharide-protein conjugates,

wherein the formulation is comprised in a siliconized container means and inhibits aggregation induced by the siliconized container means.

Dependent claim 18 recites: The formulation of claim 1, wherein the one or more polysaccharide-protein conjugate comprises [13 different S. pneumoniae serotype polysaccharides conjugated to a CRM₁₉₇ polypeptide].

Merck filed two petitions for inter partes review (IPR), IPR2017-00378 and IPR2017-00380. Both petitions challenged claims 1–6, 10, 11, 14, and 17–20. Merck’s obviousness challenge of claim 1 was based on Chiron, Smith, and Elan in the ‘378 IPR, and Chiron and Prevenar in the ‘380 IPR. With respect to claim 18, in each IPR, Merck added Peña to the combinations of references raised against claim 1. Peña disclosed a “13-valent pneumococcal conjugate vaccine with the same serotypes recited by claim 18, but not conjugated to the CRM₁₉₇ protein.”

PTAB: The Patent Trial and Appeal Board (PTAB) issued two Final Written Decisions holding all the challenged claims, except for claim 18, unpatentable as obvious. As to claim 18, the PTAB stated it was “unable to assess whether the study  [disclosed in Peña] involved a formulation comprising each of the thirteen known serotypes conjugated to a CRM₁₉₇ polypeptide [the carrier protein], as required by the claim, or if such an attempt was even considered, tried, and successful.” IPR2017-00378, Paper 59, at 44. 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,” (Id. at 39) 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 appealed both IPR decisions.

Federal Circuit: The Federal Circuit issued one decision for both IPRs, concluding that the PTAB did not provide a reasoned basis for upholding claim 18 in either Final Written Decision, citing precedent noting that:

“[t]he agency tribunal must make findings of relevant facts, and present its reasoning in sufficient detail that the court may conduct meaningful review of the agency action.” In re Lee, 277 F.3d 1338, 1346 (Fed. Cir. 2002). “The [Board]’s own explanation must suffice for us to see that the agency has done its job and must be capable of being ‘reasonably . . . discerned’ from a relatively concise [Board] discussion.” In re NuVasive, Inc., 842 F.3d 1376, 1383 (Fed. Cir. 2016) (quoting In re Huston, 308 F.3d 1267, 1281 (Fed. Cir. 2002)).

Merck, at *4.

Merck’s expert testified (without contradiction from Wyeth’s expert) that early pneumococcal polysaccharide vaccines included 14-valent and 23-valent unconjugated vaccines which, together, included all 13 serotypes recited in the claim, and that it would have been obvious to combine them into a single vaccine. This evidence was not rebutted.

But would it have been obvious to conjugate the 13 serotypes recited in the claim to the CRM₁₉₇ protein in a single vaccine? The Federal Circuit found the PTAB’s conclusion that Peña did not show such an attempt “was even considered, tried and successful[,]” insufficient to support a lack of motivation or reasonable expectation of success. Id. at *7. “Obviousness, unlike anticipation, does not require a prior art successful formulation.” Id. There was also evidence that Chiron identified CRM₁₉₇ as a “particularly preferred” carrier protein and “[Peña] describes the 9-valent version of the vaccine as being conjugated to only the single CRM₁₉₇ carrier.” Id. There was conflicting testimony about whether the prior art disclosed an 11-valent pneumococcal CRM₁₉₇ conjugate vaccine. And there was conflicting testimony as to whether a POSITA would “conclude that the 7-valent conjugate vaccine . . . could be expanded to the 13-valent pneumococcal polysaccharide single-carrier CRM₁₉₇ conjugate vaccine” with a reasonable expectation of success. Id.  at *8. The Federal Circuit found that that PTAB should have addressed the conflicting evidence as to motivation to modify and reasonable expectation of success.

The Federal Circuit also found that the PTAB failed to address the evidence and factual issue of whether a POSITA “would have been dissuaded from using a single carrier protein (i.e. CRM₁₉₇) due to ‘immune interference.’” Id.  at *9. According to the Federal Circuit:

The fact that Peña did not disclose such a combination fails to answer this central question, and an 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. (emphasis added)

Merck, at *10.

Practical Takeaways

The legal conclusion that a claim would have been obvious depends on at least the four underlying factual issues set forth in Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17, 86 S.Ct. 684, 15 L.Ed.2d 545 (1966): (1) the scope and content of the prior art; (2) differences between the prior art and the claims at issue; (3) the level of ordinary skill in the pertinent art; and (4) evaluation of any relevant secondary considerations. All four factors must be addressed. Kinetic Concepts, Inc. v. Smith & Nephew, Inc., 688 F.3d 1342,1360 (Fed. Cir. 2012). It generally remains best practice to try to attack rather than rebut a prima facie case of obviousness in light of prosecution history estoppel and litigation implications. 

A patentee, however, might shore up the defenses against a third party petitioning for an IPR with rebuttal evidence such as unexpected results. In such cases, the PTAB sometimes relied on evidence rebutting a prima facie case during prosecution to support denial of the IPR. Coalition for Affordable Drugs V LLC v. Hoffman-LaRoche, Inc., IPR2015-01792, Paper 14 (P.T.A.B. Mar. 11, 2016)  (institution for failure to address objective indicia considered by Examiner during original prosecution); and Merial Ltd. v. Virbac, IPR2014-01279, Paper 13 (P.T.A.B. Jan. 22, 2015) (denying institution for failure to address objective indicia considered by Examiner during original prosecution and noting “Merial was aware of the unexpected results showing which the Examiner found persuasive . . . . Merial should have addressed unexpected results in the first instance.”).

It is well established that the PTAB must support its conclusion with reasoning. In Merck, the Federal Circuit cites several cases on this point. See, e.g., In re Lee, 277 F.3d 1338, 1342  (Fed. Cir. 2002) (“when the issue is obviousness,… ‘[t]he factual inquiry whether to combine references must be thorough and searching.’ … It must be based on objective evidence of record. This precedent has been reinforced in myriad decisions, and cannot be dispensed with.”). See also, In re Stepan Co., 868 F.3d 1342 (Fed. Cir. 2017); In re Grose, 592 F.2d 1161 (CCPA 1979)(an examiner must provide some evidentiary basis for the existence and meaning of the scientific principle relied on in support of an obviousness rejection); and Arendi S.A.R.L. v. Apple Inc., 832 F.3d 1355 (Fed. Cir. 2016).

Therefore, as a patent owner, challenge any unsupported conclusions or reliance on only common sense by either an Examiner or PTAB.

Furthermore, it is improper in determining whether a person of ordinary skill would have been led to a combination of references simply to “[use] that which the inventor taught against its teacher.”  In re Lee, 277 F.3d at 1343, citing W.L. Gore & Assocs. v. Garlock, Inc., 721 F.2d 1540, 1553 (Fed. Cir. 1983). See also, In re Dow Chem. Co., 837 F.2d 469, 473 (Fed. Cir. 1988) ("[t]here must be a reason or suggestion in the art for selecting the procedure used, other than the knowledge learned from the applicant's disclosure” and “[b]oth the suggestion and the expectation of success must be founded in the prior art, not in applicant's disclosure."); Cardiac Pacemakers, Inc. v. St. Jude Medical, Inc., 381 F.3d 1371 (Fed. Cir. 2004). A patentee, therefore, should challenge hindsight reasoning by the PTAB or an Examiner that relies on the patentee’s specification as a roadmap to the claimed subject matter.