Recently, Pfizer was denied institution of two follow-on inter partes review (IPR) petitions, IPR Nos. 2018-00330 and 2018-00331 (“the 2018 petitions”), filed on December 18, 2017, asserting invalidity of Genentech patents, U.S. 6,339,142 (“the ’142 patent”) and U.S. 9,249,218 (“the ’218 patent”).  The Patent Trial and Appeal Board (“the Board”) denied instituting the IPRs using its discretion under 35 U.S.C. § 314(a) in light of the factors applied in Nvidia[1] and General Plastics[2].  The decision reached by the Board illustrates the need to explain the rationale for follow-on petitions clearly and in light of the General Plastics doctrine.

Genentech’s patents are directed to anti-HER2 antibody compositions and generally disclose purification procedures using ion exchange chromatography to resolve the antibodies from one or more contaminants or “variants.”  Genentech’s patents claim a composition comprising a mixture of anti-HER2 antibody and one or more acidic variants thereof, wherein the amount of the acidic variant(s) is less than about 25%, and wherein the anti-HER2 antibody is humMAb4D5-8.  The claims of the ’218 patent further require that the acidic variant(s) are predominately deamidated variants, wherein one or more asparagine residues of the anti-HER2 antibody have been deamidated, and wherein the deamidated variants have asparagine 30 in CDR1 of either or both variable light regions converted to aspartate.

The 2018 petitions came on the heels of two earlier IPRs, IPR Nos. 2017-02019 and 2017-02020 (“the 2017 petitions”), filed on August 29, 2017, by Pfizer against the’142 patent and the ’218 patent using Andya, Waterside, and Harris as prior art references[3], which were similarly asserted in both the 2017 and 2018 petitions[4].  In particular, Pfizer asserted in its 2017-02020 petition against the ’218 patent that Andya anticipates the claims because Andya discloses an anti-HER2 composition comprising full length humanized huMAb4D5-8 and acidic variants thereof.  Pfizer pointed to disclosures in Andya, stating that the anti-HER2 antibody was observed to degrade by deamidation of asparagine 30.  Notably, Pfizer also asserted that Andya inherently discloses deamidated variants with asparagine 30 of CDR1 of a variable light chain converted to aspartate because Andya teaches that asparagine 30 in the light chain is deamidated and asparagine necessarily converts to aspartate when humMAb4D5-8 deamidates.

In support of its arguments, Pfizer also submitted expert declarations that would ultimately be an issue in the Board’s decision of whether or not to institute the 2018 petitions.  In particular, Pfizer submitted the declaration of Dr. Buick in support of their assertion of inherent anticipation by showing that Dr. Buick could prepare humMAb4D5-8 compositions using the disclosures provided in the asserted prior art references and arrive at a composition that meets all the limitations of the challenged claims.

The Board decided to institute Pfizer’s 2017 petitions, concluding that Pfizer had shown a reasonable likelihood that it would prevail in showing unpatentability of the disputed claims over Andya and Harris.  However, the Board decided to exercise its discretion by declining to proceed on the grounds involving Waterside, which was comprised of slides depicting the work of Harris and which were presented at a conference approximately one year after publication of Harris.

Prior to institution of the 2017 petitions and four days after the patent owner’s preliminary response in those proceedings, Pfizer filed the 2018 petitions asserting that the disputed claims are invalid over Andya, Waterside, and Harris.  Of note in the 2018 petitions, Pfizer included an expert declaration by Dr. Buick showing additional experiments using a different cell line than the cell line used in the 2017 petitions and a second declaration supporting the Waterside reference as a printed publication within the meaning of section 102.  Pfizer filed an unsuccessful motion for joinder of the follow-on petitions.

In response to the 2018 petitions, Genentech argued that Pfizer offered new evidence and arguments in the 2018 petitions using the same prior art references to attack the same claims and failed to provide any rationale for why the follow-on petitions should be instituted in light of the General Plastics doctrine.  We previously outlined the General Plastics factors here.

The Board agreed with Genentech and denied institution of the 2018 petitions citing the factors applied in General Plastics.  Factors 2 and 3 weighed heavily on the Board’s decision not to institute.  In particular, Pfizer relied upon a new declaration from Dr. Buick describing a second set of experiments aimed at producing humMAb4D5-8 with the claimed amount of variants in HEK cells.  Genentech argued that the first petition could have provided those experiments in the first petition, and moreover Pfizer should have provided those experiments in the first petition because the time stamp shows that Dr. Buick completed the experiments prior to the filing of the first petition.

Genentech also asserted that Pfizer used their patent owner’s preliminary responses in the 2017 petitions, filed four days before Pfizer filed the 2018 petitions, as a road map to refine the 2018 petitions[5]. In that regard, Genentech contended that the 2018 petitions merely address what they contend are major deficiencies in Pfizer’s assertions that they highlighted in their responses to the 2017 petitions.  For example, Genentech argued that Dr. Buick’s experiments failed to demonstrate the prior art was enabling because he used CHO cells instead of the HEK cells employed in the prior art references, and new experiments by Dr. Buick in the 2018 petitions now included experiments using HEK cells.  Genentech also argues that Pfizer attempted to address what it contended are deficiencies in their declaration supporting Waterside as a valid printed publication available to the public as prior art.

In regard to factors 4 and 5, Genentech argued that Pfizer’s new petitions used the same prior art references and failed to provide any explanation for why the new evidence was not previously presented.  Genentech argued that Pfizer’s only justification for the follow-on petitions was that the 2018 petitions are substantively identical to the original petitions as stated in their motion for joinder.  Along that same vein, Genentech argued that factor 6 also disfavors institution because the 2018 petitions are amongst 15 others filed by Pfizer against Genentech’s anti-HER2 patents, which they contended put a strain on the Board’s finite resources.  Finally, Genentech also contended that Pfizer’s staggered petitions challenge the statutory requirement that the Board resolve a petitioner’s challenge to a patent claim’s validity within one year of institution.

Here, the Board found Genentech’s arguments persuasive and denied institution in light of the General Plastics factors outlined by Genentech in their response. The Board also indicated that institution would be denied under § 325(d) because both petitions rely on similar disclosures from the same prior art to make substantially the same arguments for both anticipation and obviousness.

Thus, the Board’s decision not to institute in view of the General Plastics doctrine in these cases was generally motivated by a lack of sufficient explanation for why the arguments provided in the follow-on petitions could not be presented earlier.

In contrast to the Board’s decision in the 2018 petitions, the Board will institute follow-on petitions where the reasons for the later filed petitions are clearly explained in light of the General Plastics factors. As we previously reported in Sanofi-Aventis U.S. LLC v. Immunex Corporation, IPR Nos. 2017-01879 and IPR2017-01884, the petitioners persuasively showed that the arguments presented in their follow-on petitions could not have been included in their original petitions because the disputed patent did not specify how to determine whether an antibody “competes with a reference antibody,” as required by the claims.  In that case, it was only after filing their petition that the patent owner endorsed two competition assays in the course of a foreign proceeding that allowed them to complete experiments included in the follow-on petitions.  The Board found the petitioners’ reasoning persuasive, reasoning that the petitioners did not appear to strategically stage prior art and arguments in multiple petitions.

Accordingly, general guidance following from this line of cases should compel petitioners filing follow-on petitions to clearly explain the rationale for why the arguments and evidence could not be earlier presented.  Particularly in instances where the same references are used, petitioners must convince the Board that they are not strategically staging their arguments, or using the original petition as a place holder while they build their arguments for later petitions.  Alternatively, patent owners can view the decision as a roadmap for arguing against institution of follow-on petitions.

[1] NVIDIA Corp. v. Samsung Elec. Co., Case IPR2016-00134 (PTAB May 4, 2016).

[2] General Plastic Indus. Co., Ltd. v. Canon Kabushiki Kaisha, Case IPR2016-01357 (PTAB Sept. 6, 2017).

[3] WO 97/04801 to Andya et al. (“Andya”); Reed J. Harris, Chromatographic Techniques for the Characterization of Human MAbs (Slides presented at the Waterside Monoclonal Conference held at the Omni Waterside Hotel in Harborside-Norfolk, Virginia on Apr. 22–25, 1996) (“Waterside”); Reed J. Harris, Processing of C-terminal Lysine and Arginine Residues of Proteins Isolated from Mammalian Cell Culture, 705 J. CHROMATOGRAPHY A 129 (1995) (“Harris”).

[4] IPR2017-02020 and IPR2018-00330 challenged claims 1 and 5-7 based on Andya, Harris, and Waterside and IPR2017-02019 and IPR2018-00331 challenged claims 1-3 based on Andya and Waterside.

[5] See General Plastic, IPR2016-01357, slip op. at 17 (“The absence of any restrictions on follow-on petitions would allow petitioners the opportunity to strategically stage their prior art and arguments in multiple petitions, using our decisions as a roadmap, until a ground is found that results in the grant of review.”).