During the week of March 4, 2019, the Patent Trial and Appeal Board (“the Board”) issued two decisions in TC 1600.  One decision denied institution of a petition, and one decision was a final decision finding all claims unpatentable.

Luitpold Pharm., Inc. v. Apicore US LLC, IPR2018-01640 (Decision Denying Institution Entered March 6, 2019): In Luitpold,Petitioner Luitpold challenged all claims of a patent on preparing substantially pure formulations of isosulfan blue dye, which is used in applications such as cancer diagnostics.  The Board denied Luitpold’s bid to institute an IPR, partly relying on similar reasoning from a concurrent district court proceeding.

The claims were generally directed to isosulfan blue compounds having a purity of at least 99.0% by HPLC.  Decision Denying Institution at 6.  In the first two of four obviousness combinations, the Petition utilized obviousness references claiming isosulfan blue purity around 86% and argued that the POSA would have been able to reach the claimed 99% purity by routine skill and other references’ disclosures, but the Board rejected this reasoning.  First, the Board found the statements in a supporting declaration insufficient to conclude that the described level of purity was reached every time, let alone that the claimed high level of purity could be reached at the priority date through ordinary skill.  Id. at 22–26.  Further, even though the Petitioner included one obviousness reference that technically reached the claimed purity level, that reference only reached that purity level through an “exhaustive purification process” that the Board found was not in the POSA’s conventional skill set.  Id. at 25.  The Board’s reasoning on Petitioner’s second set of obviousness combinations was similar, with the same result, given that the Petitioner used a similar primary reference that would still require further purification to reach the claimed 99% isosulfan blue purity.  See id. at 27–29.

UPL Ltd. v. Agrofresh Inc., IPR2017-01919 (Final Decision Finding All Claims Unpatentable): In UPL, Petitioner UPL succeeded in proving all claims unpatentable by a preponderance of the evidence.  The patent at issue claimed “metal coordination polymer networks” (MCPNs) for storing volatile 1-methylcyclopropene complexes, which are useful in extending harvested plants’ shelf life.  Final Written Decision at 4–5.  Specifically, the patent claimed that MCPNs, unlike previous methods for storing 1-methylcyclopropene, allowed the volatile compound to adsorb into the polymer network until it was ready to be released (by contacting with water, etc.).  Id.

After rejecting Patent Owner’s bids to narrow the Institution Decision’s preliminary claim constructions (see id. at 10–18), the Board agreed with Petitioner that all claims were either anticipated by or obvious over the references in Petitioner’s first and second grounds, not reaching Petitioner’s third and fourth grounds that alleged similar anticipation and obviousness arguments.  Id. at 23–49.  Specifically, the Board found that Petitioner’s ground 1 anticipation reference disclosed all elements of the claimed MCPN complexes of claims 1–5 and 21 (id. at 23–33), and two other references combined with Petitioner’s anticipation reference rendered obvious the remaining claims, which were directed to a kit and methods of releasing the 1-methylcyclopropene from the kit.  Id. at 33–48.

During the week of March 11–15, 2019, the Patent Trial and Appeal Board (“Board”) issued 1 IPR non-institution decision, 1 IPR institution decision, and 4 IPR final written decisions (on the same patent) in TC 1600.

Alvogen Pine Brook LLC v. Celgene Corp., IPR2018-01714

The Board denied institution of Alvogen Pine Brook LLC’s (“Alvogen”) petition which challenged as obvious claims 1–15 of U.S. Patent No. 7,968,569 (“’569 patent”), assigned to Celgene Corporation (“Celgene”).  The challenged claims are directed to administering about 5–25 mg/day of lenalidomide (REVLIMID®, previously REVIMID), depicted below, for 21 consecutive days of a 28-day cycle (a “21 + 7 cyclic dosing regimen”), in combination with seven days of 40 mg/day dexamethasone, to treat multiple myeloma, a type of blood cancer.

Petitioner Alvogen argued that at least the following were specifically known:

  • drug cycling was common in multiple myeloma (“MM”) and cancer therapies to allow blood counts to rebound;
  • thalidomide had been used alone and in combination with dexamethasone (“thal-dex”), to treat MM, including in 28-day and monthly cycles;
  • dexamethasone at 40 mg/day had been administered in combination with thalidomide on days 1–4 of a monthly cycle;
  • Immunomodulatory Imide Drugs, or IMiDs—which include lenalidomide—are structural analogs of thalidomide, designed to be more potent and have a better safety profile. In vitro testing showed “direct activity” against MM, combining dexamethasone improved anti-proliferative effects, and the overall results provided the “framework” for additional testing;
  • Celgene’s press release disclosed that “Revimid” was Celgene’s “lead Immunomodulatory Drug (IMiD(TM)) for the treatment of multiple myeloma,” was a more potent analog of thalidomide, and had been successfully administered in two Phase I/II clinical trials for MM using daily doses of 5 mg, 10 mg, 25 mg, or 50 mg for 2 or 4 weeks” without significant side effects;
  • Celgene’s press release disclosed that “Celgene’s patent portfolio now includes U.S. Patent No. 6,281,230 that covers the use of REVIMID(TM), Celgene’s lead IMiD(TM) (Immunomodulatory Drug), to treat cancer . . . both as a single agent and in combination with other therapies,” and provided a hyperlink to “the chemical structure of Revimid”;
  • Claim 22 of U.S. Patent No. 6,281,230 disclosed a method of treating an oncogenic or cancerous condition using the above-identified lenalidomide structure, including in combination with a second therapeutic agent such as a steroid; and
  • an MM treatment involving other compounds (hexamethylmelamine and prednisone) using a 21+7 cycle.

See IPR2018-01714, Paper 1 (Petition), at 8–29; see also IPR2018-01714, Paper 7 (Decision) at 9–16.  Given this knowledge, Petitioner argued that the claims were obvious.

The Board issued its decision “expressly confine[d]” to what it described as “an evidentiary gap in the Petition” relating to the claimed “21+7 cyclic dosing regimen,” and specifically declined to address the substantive merits of the cited art.  IPR2018-01714, Paper 7, at 8 and n.10.  In a limited decision, the Board determined that because the five prior art references were “silent” on rest periods and the claimed 21+7 dosing regimen, the Petitioner had an evidentiary gap that was not “bridged by the background references or the opinion testimony advanced in the Petition . . . .”  Id. at 9–10.

Rimfrost AS v. Aker BioMarine Antarctic AS, IPR2018-01730

The Board granted institution of Rimfrost AS’s (“Rimfrost”) petition which challenged as obvious claims 1–20 of U.S. Patent No. 9,072,752 (“the ’752 patent”), assigned to Aker Biomarine Antarctic AS (“Aker Biomarine”).  Among other related petitions, the Board previously found unpatentable claims 1–19 of related patent U.S. Patent No. 9,028,877, see IPR2017-00746, Paper 23, and found unpatentable claims 1–20 of related patent U.S. Patent No. 9,078,905, see IPR2017-00745, Paper 24.  Read more here. Additionally, the Board instituted review of two related Petitions concerning U.S. Patent 9,375,453.  See IPR2018-01178 and IPR2018-01179. Read more here.

The challenged claims are generally directed to a polar krill oil comprising approximate percentages of certain compounds (e.g., phospholipids, triglycerides).  Petitioner Rimfrost asserted that certain claims were anticipated under § 102(e) by one reference and the remainder of the claims were collectively rendered obvious under § 103(a) by five combinations of references.  Aker Biomarine did not file a Preliminary Response.

Anticipation of claims 1, 5, 6, and 11: The Board instituted on anticipation of claim 1: the prior art (“Catchpole”) included a table showing 39.8% phosphatidylcholine and 4.8% ether phospholipids, which met independent claim 1’s “about 40%” and “about 5%” values for those components.  IPR2018-01730, Paper 7, at 9–10.  The Board also instituted on anticipation of dependent claim 11, which added a limitation that the krill oil composition was for oral administration to a human.  See id. at 12.  However, the Board found that Petitioner had not, at this stage, demonstrated that claims 5 and 6 were reasonably likely to be anticipated.  These claims respectively required greater than 6% or 7% of ether phospholipids, and the Board reasoned that Catchpole’s disclosure that compositions could contain greater than 10% acylalkyphospholipids was not an actual disclosure of a krill oil composition having that amount of acylalkyphospholipids.  See id. at 11–12.

Five grounds of obviousness, collectively of claims 1–20: The Board also instituted on obviousness of claims 1–20 using combinations of Catchpole with up to four other pieces of art.  See generally id. at 12–21.  In short, the Board agreed that Petitioner Rimfrost has established a reasonable likelihood that the claims were obvious given that other pieces of prior art disclosed the other elements of the claims, including the genus and species of the krill phospholipid composition, see id. at 12–14, 15; components of the krill composition, see id. at 14, 15–16 (astaxanthin); percentages of krill components (phosphatidylcholine, phospholipids, triglycerides), see id. at 17–20; oral formulations for human administration (including capsules), see id. at 14, 18–19, 20; and treatment of human diseases, see id. at 15, 18–19.

Merck Sharp & Dohme Corp. v. Pfizer Inc., IPR2017-02131, -02132, -02136, and -02138

The Board issued four final written decisions on a single patent challenged by Merck Sharp & Dohme Corp. (“Merck”)—U.S. Patent No. 9,492,559 (“the ’559 patent”)—and assigned to Pfizer Inc. (“Pfizer”), collectively finding all claims (1–45) unpatentable. See IPR2017-01231, Paper 59 (1–10, 16–19, and 38–45 unpatentable); IPR2017-02132, Paper 59 (same); IPR2017-02136, Paper 43 (claims 11–15 and 20–37 unpatentable); IPR2017-02138, Paper 45 (same).  Petitioner Merck’s four IPR petitions overlapped by providing two general approaches to two groupings of claims: IPR2017-02131 and -02132 contested as obvious the same claims (1, 3–10, 16–19, 38–45) using different art (primary references Merck 2011 and, respectively, GSK 2008 or Pfizer 2012) whereas IPR2017-02136 and -02138 contested the obviousness of another set of claims (11–14, 20–37) using the same approach (primary references Merck 2011 and, respectively, GSK 2008 or Pfizer 2012).

Note: Merck filed additional IPR and PGR petitions on related U.S. Patent Nos. 9,399,060 (IPR2017-01211, -01215, -01223, PGR2017-00016, -00017; institution denied on all); 8,895,024 (IPR2017-01194, institution denied); and 8,562,999 (IPR2017-00378, -003380, and -00390, collectively finding unpatentable all but dependent claim 18).  Read more here.

The ’559 patent generally relates to pneumococcal vaccines, particularly serotypes not covered by existing vaccines (such as PREVNAR 13®, the tridecavalent (13-serotype) vaccine).  See, e.g., IPR2017-02131, Paper 59, at 3–5.  Independent claim 1, the sole independent claim, recited an S. pneumoniae immunogenic composition having a specific molecular weight range, a specific isolated capsule polysaccharide and a carrier protein, and a specific ratio of the two.  See, e.g., id. at 5.  Dependent claims generally related to specific glycoconjugates and compositions, carrier proteins, formulations and formulation components, concentrations and ratios, adjuvants, antigens, and methods of using the above.  See generally ’559 patent, claims 2–45.

Primary reference Merck 2011 taught a multivalent immunogenic composition of 15 distinct polysaccharide-protein conjugates, each with a capsular polysaccharide from S. pneumoniae conjugated to a carrier protein.  See, e.g., IPR2018-02131, Paper 59, at 13.  Merck 2011 also provided additional information including concentrations/ratios and purification.  See, e.g., id. at 13–14.  GSK 2008 taught an S. pneumoniae vaccine with conjugated capsular saccharide antigens, including certain preparations, ratios, conjugates, and stabilization by saccharides.  See, e.g., id. at 13–14.  Pfizer 2012 taught glycoconjugate vaccines using chains of carrier proteins conjugated to polysaccharide antigens, including those with specific mass ranges, conjugation to proteins, and conjugate techniques.  See, e.g., IPR2018-02132, Paper 59, at 14–15.  Petitioner Merck also provided other references relating to the general knowledge in the art.  See, e.g., id. at 27–28.

Among other arguments, Patent Owner Pfizer argued that there were numerous variables which prevented predictability of outcome, thus any optimization was not routine.  See, e.g., IPR2017-02131, Paper 59, at 19–20, 23–24, 55.  The Board considered the deposition testimony of both experts but sided with Petitioner Merck, see, e.g., id. at 24–26, 34–35, 38–39, 46–47, 49, focusing on whether variables (such as conjugate size or polysaccharide-to-carrier protein ratio) were “known,” “results effective variables” or “results-optimizable variables” with known beneficial attributes providing motivation to optimize and through routine techniques, see, e.g., id. at 26, 33–34, 35–36, 47; cf. IPR2017-02132, Paper 59, at 19–27; IPR2017-02136, Paper 43, at 19–27; IPR2017-02138, Paper 45, at 20–29 (all similar).  Indeed, the Board drew a distinction between routine optimization over what was known and what was “necessarily” true, explaining that the analysis was “the obviousness of routine optimization . . . not inherent anticipation.”  See, e.g., IPR2017-02131, Paper 59, at 26; see also id. at 55 (“[T]he requirement is not an absolute expectation of success, but rather a reasonable expectation of success based on the teachings of the prior art.  ‘Obviousness does not require absolute predictability of success . . . all that is required is a reasonable expectation of success.’” (citation omitted)).  Relatedly, the Board rejected alleged deficiencies in individual pieces of “general knowledge” prior art, focusing instead on whether the disclosures “[c]onsidered as a whole” provided evidence of a “known optimizable variable” and whether they “underline[d] the basic teachings” of the primary reference(s).  See, e.g., id. at 30–34; cf. IPR2017-02132, Paper 59, at 31–32; IPR2017-02136, Paper 43, at 33; IPR2017-02138, Paper 45, at 32–33 (all similar).

During the week of March 18, 2019, the Patent Trial and Appeal Board (“the Board”) issued the following decision in TC 1600 instituting a post-grant review:

Hybrigenics SA v. Forma Therapeutics, Inc., No. PGR2018-00098 (Decision Granting Institution of Post-Grant Review Entered March 20, 2019). The Board instituted a post-grant review (“PGR”) sought by Hybrigenics SA (“Hybrigenics”) against U.S. Patent No. 9,840,491 (“the ’491 patent”) owned by Forma Therapeutics, Inc. (“Forma”). Hybrigenics raised three grounds for challenge: lack of written description, lack of enablement, and obviousness. PGR2018-00098, Paper 10 at 9. Forma, in turn, challenged Hybrigenics’s identification of real parties in interest. Despite finding issues with the enablement and obviousness grounds, the Board found the written description challenge was sufficiently established and instituted PGR on all grounds.

The claims at issue cover inhibitors of “ubiquitin-specific protease 7,” or USP7, which have potential to treat cancers and other disorders. The claims specifically cover compounds of a certain chemical formula and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers of those compounds. Id. at 3.

The Board first considered Forma’s challenge to the identification of real parties in interest; according to Forma, a third party collaborating with Hybrigenics and two U.S. subsidiaries of Hybrigenics should have been listed. Id. at 11. The Board disagreed because Forma presented no evidence that (1) the third party controlled, directed, financed, or participated in the PGR petition; or (2) the two U.S. subsidiaries were involved in the petition, that Hybrigenics served as their proxy, or that they were intermediaries through which a real party in interest exercised control. Id. at 14–18.

Turning to the written-description grounds, Forma asked the Board to deny review under § 325(d) because a patent examiner supposedly considered Hybrigenics’s arguments during prosecution. Id. at 19. Forma had narrowed the claims to overcome a § 112 rejection and assured the examiner the added limitations had written support. Id. at 20. In the PGR petition, Hybrigenics claimed this same language was unsupported. Rejecting the § 325(d) argument, the Board found no evidence that the examiner had considered Forma’s assurances, or that the rejection overlapped with Hybrigenics’s petition arguments. Id. at 20–21. On the merits, the Board concluded it was more likely than not that the added claim language lacked support. Id. at 25. Forma had limited the possible substituents of the claimed compound from “heteroaryl” and “heterocycloalkyl,” generally, to 5- or 6-membered heteroaryl and 3- to 7-membered heterocycloalkyl, but had defined “heteroaryl” and “heterocycloalkyl” broadly in the specification with numerous examples and no guidance towards the narrower constituents it later claimed. Id. at 22–24. The Board thus instituted PGR. Id. at 26. It then briefly dismissed Hybrigenics’s second written description argument—that the broad genus of claim compounds lacked written support because the specification only gave 13 exemplary compounds—concluding that Hybrigenics failed to address the commonality of any structural features of the genus, the state of the art, the predictability of the technology, or the representativeness of the 13 examples. Id. at 27–28.

The Board next found that Hybrigenics failed to establish likely unpatentability for lack of enablement. Hybrigenics had argued that skilled artisans would be unable to synthesize the millions of claimed compounds without undue experimentation, given only four synthesis examples were disclosed in the patent and artisans would not know which of the claimed compounds were effective USP7 inhibitors. Id. at 30. But, according to the Board, Hybrigenics and its expert failed to explain why the general synthesis methods and four disclosed examples were insufficient to enable synthesis of the claimed genus, the degree of experimentation that would be needed, or why the two disclosed assays were insufficient to assess USP7 inhibition. Id. at 31–32.

Finally, the Board considered the obviousness grounds. It noted that Hybrigenics failed to establish likely unpatentability on this basis, but nevertheless instituted PGR on all grounds per PTO guidance. Hybrigenics had asserted obviousness over a prior art patent that disclosed fourteen compounds. According to Hybrigenics, skilled artisans would have modified those compounds in obvious ways, and those modified compounds rendered the claimed compounds obvious. But according to the Board, Hybrigenics used impermissible hindsight because it started with the claimed compounds and argued their substituents were obvious in light of the prior art, instead of explaining why skilled artisans would have modified the prior art compounds to arrive to the claimed compounds. Id. at 41–42. Hybrigenics had also argued that examples in the prior art patent rendered certain claimed compounds obvious, but the Board noted Hybrigenics’s expert failed to cite any prior art references that suggested the required modifications. Id. at 46-47.