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).