During the week of April 8, 2019, the Patent Trial and Appeal Board (“the Board”) issued two final decisions and six decisions instituting inter partes review. The six institution decisions involved two sets of actions, each with three related proceedings.
Incyte Corporation v. Concert Pharmaceuticals, Inc., IPR2017-01256, Paper No. 119 (Final Decision Finding all Challenged Claims Unpatentable): Petitioner Incyte Corporation (“Incyte”) filed a petition requesting an inter partes review of claims 1–15 of U.S. Patent No. 9,249,149 (“the ’149 patent”), titled “Deuterated Derivatives of Ruxolitinib.” Ruxolitinib is approved for treating myelofibrosis but has other potential therapeutic applications, such as the treatment of essential thrombocytopenia, psoriasis, and cancer.
The ’149 patent has two independent claims directed towards the chemical structure of ruxolitinib with ten and eight Markush groups, respectively. IPR2017-01256, Paper No. 119 at 6–7. The Markush groups are either hydrogen, deuterium, or can be selected from hydrogen or deuterium. Id. The dependent claims recite (1) specific deuteration patterns of ruxolitinib and (2) pharmaceutical compositions containing the deuterated ruxolitinib compounds. Id. at 7.
Incyte challenged the claims of the ’149 patent as obvious on two separate grounds, both involving a combination of three references. Id. at 8. The decision turned on whether one reference used in both grounds was publicly available before the patent’s critical date. Id. at 14-15. The reference at issue was one of Concert Pharmaceuticals’s own publications. Id. Incyte prevailed in establishing public availability by showing (1) a cached WebCite© page, (2) a law review article published before the critical date that included the same WebCite© page, and (3) an International Search Report for a PCT application that cited the reference. Id. at 15-19.
The Board assessed the obviousness of the claims using a “lead compound” analysis. IPR2017-01256, Paper No. 119 at 20. The Board determined “that the preponderance of the evidence supports finding that a person of ordinary skill in the art would have chosen ruxolitinib as a lead compound” and that one of the references cited by Incyte expressly claimed ruxolitinib and its isomers. Id. at 21. In addition, the Board found that the combination of the three references provided a reason to deuterate ruxolitinib compounds at their metabolic hot spots to achieve the same benefits and properties disclosed in the ’149 patent. Id. at 23.
Finally, with respect to secondary considerations, Concert argued that the claims yielded unexpected results and satisfied a long-felt need. Id. at 33. With respect to unexpected results, Concert asserted that the claimed deuterated compounds provide an increased (1) time in the therapeutic window relative to the prior art ruxolitinib and (2) clinical response at a given dose. Id. The Board held that these results were “merely a difference in degree and not in kind” and as such do not support a finding of nonobviousness. Id. at 34. Concert also argued that “[t]here has been a long-felt need for an alopecia areata treatment that is not only effective, but also safe for prolonged use.” Id. at 35 (alteration omitted). The Board held that the claimed compounds have not satisfied the long-felt need because the data so far shows only promise and no FDA approval has been obtained for this particular use. Id. at 36–37.
The Board concluded that based on the preponderance of the evidence, the challenged claims are unpatentable as obvious in light of the prior art. Id. at 37, 51.
Nuseed Americas Inc. v. BASF Plant Science GmbH, IPR2017-02176, Paper No. 51 (Final Decision Finding all Challenged Claims Unpatentable): Petitioner Nuseed Americas Inc. (“Nuseed”) filed a petition challenging claims 20–22 of U.S. Patent No. 7,777,098 (“the ’098 patent”). IPR2017-02176, Paper 51 at 2. The ’098 patent is owned by BASF Plant Science GmbH (“BASF”). Id.
Independent claim 20 of the ’098 patent recites a process for producing polyunsaturated fatty acids in transgenic organisms using a specific enzyme. Id. at 5. Dependent claims 21 and 22 add limitations regarding the number of double bonds in the fatty acids and the type of transgenic organism. Id.
The Board instituted trial based on all grounds of unpatentability under (1) 35 U.S.C. § 102(e), (2) 35 U.S.C. § 102(b), and (3) § 103(a). IPR2017-02176, Paper No. 51 at 6. But having first found the § 102(e) grounds of unpatentability persuasive, the Board did not consider the § 102(b) or § 103(a) grounds at the institution phase. Id. at 12. The prior art reference cited by Nuseed disclosed methods for producing polyunsaturated fatty acids using microorganisms. Id. at 9–10. That reference contains an example that teaches producing the specific polyunsaturated fatty acids claimed in the ’098 patent using a transgenic microorganism expressing the claimed enzyme. Id. The Board concluded that this prior art reference discloses every limitation of, and, therefore anticipates, claims 20–22 of the ’098 patent. Id. at 11.
BASF also filed a motion to amend. Id. at 12. The proposed substitute claims added a limitation to independent claim 20 specifying a specific polyunsaturated fatty acid capable of being desaturated by the enzyme. Id. Nuseed asserted that the substitute claims were unpatentable as anticipated by, or obvious in view of, two additional prior art references. Id. at 14. The Board agreed that one of those references anticipated the substitute claims and denied BASF’s motion to amend. Id. at 24.
Hubei Grand Life Science & Technology Co. v. Vitaworks IP, LLC (Decisions Instituting Inter Partes Review): The Board instituted three related inter partes reviews involving petitioner Hubei Grand Life Science and Technology Co., Ltd. (“Hubei”) and patent owner Vitaworks IP, LLC (“Vitaworks”). All three IPRs involve patents that claim processes for producing taurine. IPR2018-01766, Paper No. 10 at 2–3; IPR2018-01767, Paper No. 10 at 2–3; and IPR2018-01768, Paper No. 10 at 2–3.
IPR2018-01766 – U.S. Patent No. 9,428,450
U.S. Patent No. 9,428,450 (“the ’450 patent”) describes “a cyclic process for the production of taurine from alkali isethionate and from alkali vinyl sulfonate in a high overall yield . . . by continuously converting the byproducts of the ammonolysis reaction, alkali ditaurinate and alkali tritaurinate, to alkali taurinate.” IPR2018-01766, Paper No. 10 at 3 (quoting ’450 patent at 1:6-11). The only independent claim reads:
A process for the production of taurine from alkali ditaurinate or alkali tritaurinate, or their mixture, comprising:
(a) adding an alkali hydroxide to a solution of alkali ditaurinate, or alkali tritaurinate or their mixture, to prepare a solution of dialkali ditaurinate, or trialkali tritaurinate or their mixture,
(b) adding an excess amount of ammonia to a solution of dialkali ditaurinate, or dialkali tritaurinate, or their mixture, and subjecting the solution to ammonolysis reaction to yield a mixture of alkali taurinates,
(c) removing excess ammonia from (b) and neutralizing alkali taurinates with an acid to form a crystalline suspension of taurine, and
(d) recovering taurine by means of solid-liquid separation.
Hubei contended that claims 1 and 3–7 of the ’450 patent were unpatentable as either anticipated by or obvious in light of three prior art references. Id. at 9. The closest reference teaches “‘a method for producing ditaurine and salts thereof from taurine or its salts’ in a reaction medium,” and Hubei contended that this reference anticipated the claims. Id. at 19. But the Board was “skeptical that [Hubei] is reasonably likely to succeed in establishing anticipation.” Id. at 22. Hubei further asserted three obviousness grounds, leading the Board to hold that “[n]otwithstanding our skepticism on the anticipation challenge, because we find that the Petition demonstrates a reasonable likelihood of success in establishing that at least one of claims 1 and 3–7 are unpatentable for obviousness . . . we include Ground 1 in the institution of trial.” Id. at 24.
IPR2018-01767 – U.S. Patent No. 9,428,451
A cyclic process for the production of taurine from alkali isethionate, comprising:
(a) adding an excess of ammonia to a solution of alkali isethionate and subjecting the solution to ammonolysis reaction in the presence of one or more catalysts to yield a mixture of alkali taurinate, alkali ditaurinate, alkali tritaurinate, and unreacted alkali isethionate;
(b) recovering the excess ammonia from (a) and neutralizing the solution with sulfuric acid to obtain a crystalline suspension of taurine in a solution of alkali sulfate, alkali ditaurinate, alkali tritaurinate, and alkali isethionate;
(c) separating taurine from (b) to provide a mother liquor
(d) adjusting the pH of the mother liquor to basic to convert taurine present in the mother liquor to alkali taurinate and prevent the crystallization of taurine, and removing alkali sulfate from the mother liquor by performing evaporative crystallization and cooling crystallization through solid-liquid separation;
(e) returning the mother liquor of (d) to (a) for further ammonolysis of alkali ditaurinate, alkali tritaurinate, and unreacted alkali isethionate.
Hubei challenged all claims on three obviousness grounds. Id. at 6. The Board agreed with Hubei that a combination of three references supported the assertion that a skilled artisan would have been motivated to combine the teachings with a reasonable expectation of success. Id. at 17. Vitaworks contended that the asserted combination of references does not teach or suggest the second ammonolysis step in claim 1. Id. The Board found this contention unpersuasive based largely on a skilled artisan’s likely reading of the prior art and determined that Hubei established a reasonable likelihood that it would prevail in showing the unpatentability of claim 1. Id. at 19–22.
IPR2018-01768 – U.S. Patent No. 9,573,890
U.S. Patent No. 9,573,890 (“the ’890 patent”) is also directed towards a process for producing taurine from alkali isethionates by carrying out an ammonolysis reaction. IPR2018-01768, Paper No. 10 at 2–3. The independent claim reads:
A process for producing taurine from alkali isethionate, comprising:
(a) mixing alkali isethionate with a solution of alkali ditaurinate, alkali tritaurinate, or their mixture in the presence of one or more catalysts;
(b) adding an excess of ammonia to the (a) and subjecting the solution to ammonolysis reaction to yield a mixture of alkali taurinate, alkali ditaurinate, and alkali tritaurinate;
(c) removing excess ammonia and neutralizing with an acid to obtain a crystalline suspension of taurine; and
(d) separating taurine by means of solid-liquid separation.
Hubei challenged the patentability of claims 1 and 3–10 on three obviousness grounds. Id. at 5. Vitaworks argued that claim 1 includes a second ammonolysis step like the ’451 patent. Id. at 8. The Board determined that the ’890 patent does not claim a second ammonolysis step because “[u]nlike in the ’451 patent, the last step recited in claim 1 of the ’890 patent, i.e., step (d), merely requires ‘separating taurine by means of solid-liquid separation,’ without any further processing or ammonolysis.” Id. at 8–9. After reviewing the prior art references, the Board determined that Hubei established a reasonable likelihood of successfully establishing obviousness. Id. at 16–17.
Eli Lilly & Co. v. Teva Pharm. Int’l GmbH, IPR2018-01710, IPR2018-01711, IPR2018-01712 (Decisions Granting Institution of Inter Partes Review Entered April 3, 2019): In three decisions issued on the same day, the Board instituted inter partes reviews against U.S. Patent Nos. 8,586,045 (“the ’045 patent”), 9,884,907 (“the ’907 patent”), and 9,884,908 (“the ’908 patent”) owned by Teva Pharmaceuticals International GmbH (“Teva”). The petitioner, Eli Lilly and Company (“Eli Lilly”), raised obviousness grounds against the three patents based on the same three-reference combination. According to the Board, Eli Lilly showed a reasonable likelihood that at least one claim of each challenged patent was unpatentable over the combined teachings of Olesen, Tan, and Queen. IPR2018-01710, Paper 12 at 34; IPR2018-01711, Paper 12 at 34; IPR2018-01712, Paper 11 at 31–32.
The ’045, ’907, and ’908 patents relate to the use of anti-Calcitonin-Gene-Related-Peptide (“CGRP”) antibodies “for the prevention, amelioration, or treatment of vasomotor symptoms, such as CGRP related headaches (e.g. migraine) and hot flushes [sic].” IPR2018-01710, Paper 12 at 4; IPR2018-01711, Paper 12 at 4; IPR2018-01712, Paper 11 at 3. The ’045 patent has two independent claims covering methods for reducing incidence of or treating “at least one vasomotor symptom in an individual” (claim 1) or “headache in a human” (claim 17) comprising administering an “effective amount” anti-CGRP antagonist antibody that is a human or “humanized monoclonal antibody.” IPR2018-01710, Paper 12 at 6. The ’907 and ’908 patents each have one independent claim covering methods of “treating headache in an individual” comprising administering an “effective amount” of a “humanized monoclonal anti-[CGRP] antagonist antibody” with certain structural elements (two human IgG heavy chains, each comprising three complementarity determining regions (“CDRs”), and two light chains, each also comprising three CDRs), wherein the CDRs impart specific binding to a CGRP consisting of certain amino acid residues of two specific sequences. IPR2018-01711, Paper 12 at 6; IPR2018-01712, Paper 11 at 5–6. The claim of the ’908 patent has an additional limitation requiring a specific binding affinity (“10 nM or less as measured by surface plasmon resonance at 37° C”). IPR2018-01712, Paper 11 at 6.
The Board first addressed claim construction. Notably, although it construed “reducing incidence of or treating” (as used in the ’045 patent) and “treating” (as used in the ’907 and ’908 patents) to not require a clinical result, the Board construed “effective amount” (present in all three patents) as requiring “achievement of beneficial or desired results.” IPR2018-01710, Paper 12 at 12; IPR2018-01711, Paper 12 at 12; IPR2018-01712, Paper 11 at 11.
On obviousness, the Board was persuaded that Olesen, Tan, and Queen sufficiently disclosed the elements of the challenged claims, even though no reference directly related to the claimed treatment of vasomotor symptoms or headaches in individuals or humans with an anti-CGRP antagonist antibody. Olesen disclosed a human clinical study involving a small-molecule antagonist of CGRP’s receptor, not a large-molecule (i.e., antibody) antagonist of CGRP itself, as claimed. IPR2018-01710, Paper 12 at 25; IPR2018-01711, Paper 12 at 26–27; IPR2018-01712, Paper 11 at 19–21. Tan disclosed an in vivo rat study using an anti-CGRP monoclonal antibody (as claimed), but not a human study, and made no specific findings related to headaches or migraines, showing only that the anti-CGRP antagonist antibody and its Fab’ fragment block the CGRP pathway. IPR2018-01710, Paper 12 at 29, 32–33; IPR2018-01711, Paper 12 at 31, 34; IPR2018-01712, Paper 11 at 24.
The Board nevertheless rejected Teva’s arguments that the references could not be combined or extended to render the challenged claims obvious. IPR2018-01710, Paper 12 at 24-25, 29; IPR2018-01711, Paper 12 at 26-27, 30–31; IPR2018-01712, Paper 11 at 25. Moreover, although Tan indicated the Fab’ fragment was more effective than the full-length antibody, the Board refuted Teva’s argument that Tan taught away from the claimed method (which involves the full-length antibody), noting that Tan actually suggested further investigating treatment with the full-length antibody. IPR2018-01710, Paper 12 at 32; IPR2018-01711, Paper 12 at 33–34; IPR2018-01712, Paper 11 at 24–25. Regarding the binding affinity limitation in the ’908 patent, the Board concluded it would have been “routine” to obtain antibodies with the claimed binding affinity. IPR2018-01712, Paper 11 at 29. Finally, the Board rejected Teva’s request to deny institution under 35 U.S.C. § 325(d) because substantially similar arguments were supposedly considered during prosecution, reasoning that at least Olesen included new, noncumulative evidence that was not previously considered. IPR2018-01710, Paper 12 at 40; IPR2018-01711, Paper 12 at 40; IPR2018-01712, Paper 11 at 38.