During the week of April 1, 2019, the Patent Trial and Appeal Board (“the Board”) issued the following decisions in TC 1600:
Dr. Reddy’s Laboratories, Inc. (“DRL”) v. Horizon Pharma USA, Inc. and Nuvo Pharmaceuticals (Ireland) Designated Activity Company (collectively referred to as “Horizon”), IPR2018-01341 (Decision Granting Petitioner’s Motion for Joinder and Instituting Inter Partes Review Entered April 1, 2019).
In its petition, DRL challenged claims 1-7 of U.S. Patent No. 9,393,208 (“the ’208 patent”), which is directed to methods for delivering a pharmaceutical composition in unit dose form of naproxen and esomeprazole. With its petition, DRL timely filed a Motion for Joinder to IPR2018-00272, filed by Mylan Pharmaceuticals, which was instituted on June 14, 2018. Horizon did not file an opposition to the joinder motion.
A motion for joinder should:
- set forth the reasons that joinder is appropriate;
- identify any new grounds of unpatentability asserted in the petition;
- explain what impact (if any) joinder would have on the trial schedule for the existing review; and
- address specifically how briefing and discovery may be simplified.
IPR2018-01341, Paper 21 at 6. In its motion, DRL acknowledged it sought review of the same claims at issue in IPR2018-00272, on the same grounds, and agreed to rely on the declarations and testimony of Mylan’s experts. Id. at 7. DRL further agreed to not file any additional papers or pages, present any new, additional, or supplemental arguments, cross-examine Horizon’s experts or offer a rebuttal expert of its own, or present any arguments at oral hearing. Id.
In view of the foregoing and the Board’s determination that DRL had demonstrated there was a reasonable likelihood it would prevail with respect to at least one of the challenged claims, DRL’s Motion for Joinder was granted. Id. at 8.
Pfizer, Inc. (“Pfizer”) v Genentech, Inc. (“Genentech), IPR2017-01923 (Termination of the Proceeding Due to Settlement after Institution with Respect to Petitioner Only Entered April 2, 2019).
In its petition, Pfizer challenged claims 1-14 of U.S. Patent No. 7,976,838 (“the ’838 patent”), which is directed to antagonists (e.g., rituximab) that bind to B cell surface markers, such as CD20, and uses of such antagonists to treat autoimmune diseases.
Independent claim 1 is representative and recites:
A method of treating rheumatoid arthritis in a human patient who experiences an inadequate response to a TNFα-inhibitor, comprising administering to the patient an antibody that binds to CD20, wherein the antibody is administered as two intravenous doses of 1000 mg.
In March 2019, Pfizer and Genentech filed a Joint Motion to Terminate. IPR2017-01923, Paper 109 at 2. Under 35 U.S.C. § 317(a), upon a joint request of the petitioner and the patent owner, the Office shall terminate an inter partes review with respect to any petitioner. However, the Board, which is not a party to the settlement, may independently determine a question of patentability should the determination be in the public’s interest. Id. at 3 (citing 37 C.F.R. § 42.74(a)).
Here, the trial was instituted in April 2018, oral arguments occurred in January 2019, and the panel had already decided the merits of the proceeding. Id. at 3. In view of the foregoing, the Board determined that substantial resources had been invested in the matter and that it was reasonable at this stage to proceed to final written decision. Id. In addition, the Board felt it was warranted to proceed because of the public’s substantial interest in the ’838 patent—five other petitions against that patent have been filed. Id.
As such, the Board granted-in-part, as to Pfizer, the Joint Motion to Terminate, but determined it would proceed to a final written decision as to Genentech.
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.
During the week of April 15–19, 2019, the Patent Trial and Appeal Board (“Board”) issued two IPR non-institution decisions (on the same patent), two PGR institution decisions, and one IPR final written decision in TC 1600.
Intervet Inc. a/k/a Merck Animal Health v. Boehringer Ingelheim Vetmedica, Inc., IPR2018-01788 and IPR2018-01789 (Decision Denying Institution Entered Apr. 16, 2019). The Board denied institution of Intervet Inc. a/k/a Merck Animal Health’s (“Intervet”) petition, which challenged as unpatentable all claims of U.S. Patent No. 9,011,872 B2 (“’872 patent”), assigned to Boehringer Ingelheim Vetmedica, Inc. (“Boehringer”). The challenged claims are directed to an “improved method of producing” or “recovering” recombinant PCV2 ORF2 protein. Production of recombinant PCV ORF2 protein (sometimes called rORF2) generally involves the steps of transfecting recombinant virus containing open reading frame 2 coding sequences into cells contained in growth media, causing the virus to express open reading frame 2, and recovering the expressed protein in the supernate.
Petitioner Intervet argued that a limitation in the ’872 patent directed to a protective effect broadly encompassed a protective effect of any magnitude, duration, or type, against any clinical symptom associated with a PCV2 infection or against PCV2 infection itself. The Board disagreed, finding that Intervet advanced an incorrect construction of the protective effect limitation; that fact, standing alone, warranted denial of the Petition because without Intervet’s proposed construction there is not a reasonable likelihood that it would prevail with respect to at least one of the challenged claims.
Alternatively, the Board rejected Intervet’s anticipation and obviousness grounds. Intervet failed to show sufficiently that the prior art discloses an immunological composition that satisfies the protective effect limitation of the challenged claims, which require an amount of recombinant PCV2 ORF2 protein sufficient to provide a protective effect against the symptoms of PCV2 infection in a single dose.
Genome & Co. v. Univ. of Chicago, PGR2019-00002 (Decision Granting Institution Entered Apr. 15, 2019). The Board granted institution on all eleven grounds of Genome & Company’s (“Genome”) petition, which challenged as unpatentable all claims of U.S. Patent No. 9,855,302 B2 (“’302 patent”), assigned to The University of Chicago. The challenged claims are directed to the treatment or prevention of cancer through the use of commensal microflora—specifically bacteria from the genus Bifidobacterium—in combination with an immune checkpoint inhibitor (“CPI”). Genome asserted that all claims lack enablement and certain claims are obvious. The Board declined to deny the petition under 35 U.S.C. § 325(d).
The claims of the ’302 patent are not limited to a specific form of cancer nor to a specific species of Bifidobacterium, and that the broader claims do not specify the CPI to be used. Thus, Genome contended that because the claims can cover “thousands of different combinations of cancers, immune checkpoint inhibitors and genera of Bifidobacterium,” the guidance given in the ’302 patent is inadequate given the scope of the claims and the unpredictable nature of the technology. The Board agreed, finding that: the working examples are markedly limited and only address two types of cancer using only one CPI and 4 species of Bifidobacterium; the specification gives no guidance as to how to select CPIs and Bifidobacterium that will work in the claimed method without resorting to trial and error; and the specification lists 36 different species of Bifidobacterium and gives a broad definition of a CPI. Thus, the Board found Genome was reasonably likely to succeed in its argument that the Wands factors show that the claims are not enabled for the full scope of the claims.
Genome also contended that prior art teaches a method for treating cancer in humans by administering CPIs such as anti-PD-1 and anti-CTLA-4 antibodies that bind to their respective immune checkpoint proteins; that oral administration of Bifidobacterium longum exerts strong antitumor activity; and that that Bifidobacterium longum is immunostimulatory, thus one skilled in the art would have been motivated to combine the teachings of the references as the CPIs and the Bifidobacterium are both shown to be effective in treating colon cancer and are both immunostimulatory. The University of Chicago responded that one skilled in the art would not use an immunosuppressive agent in combination with an immunostimulatory agent, and, therefore, would not have combined the prior art’s purportedly immunosuppressive bifidobacterium with its immunostimulatory CPIs. The Board again found Genome demonstrated a reasonable likelihood of success and instituted trial as to all challenged claims on all grounds asserted.
Adello Biologics LLC, Apotex Inc., and Apotex Corp. v. Amgen Inc. and Amgen Mfg. Ltd., PGR2019-00001 (Decision Granting Institution Entered Apr. 19, 2019). The Board granted institution on all grounds of Adello Biologics LLC, Apotex Inc., and Apotex Corp.’s (collectively “Petitioners”) petition, which challenged as unpatentable all claims of U.S. Patent No. 9,856,287 B2 (“’287 patent”), assigned to Amgen Inc. and Amgen Manufacturing Ltd. (“Amgen”). The challenged claims are generally directed to a method of refolding proteins expressed in non-mammalian cells. Petitioners asserted unpatentability based on lack of adequate written description, lack of enablement, anticipation, obviousness, and indefiniteness. The Board declined to deny the petition under 35 U.S.C. § 325(d) or for delayed identification of a real party in interest.
With respect to the prior-art grounds, Amgen argued in response to Petitioner’s anticipation and obviousness assertions that the prior art discloses the ratio of the concentration of reductant to the concentration of oxidant, not the actual concentrations of reductant and oxidant used, and without the actual concentration one cannot deduce the concentrations of the oxidant and reductant or the thiol-pair ratio. While the Board tended to agree that Petitioner had demonstrated a reasonable likelihood of success at this stage, it noted that the parties may more fully develop the record during trial before it resolves this dispute.
With respect to the written-description ground, the Board was persuaded, based upon the current record, that there was a reasonable likelihood that certain claims may be unpatentable under 35 U.S.C. § 112(a) based upon the argument that the specification of the ’287 patent does not provide adequate written description support for “at least about 25% of the proteins are properly refolded.”
The Board was also persuaded on the current record that Petitioner demonstrated a reasonable likelihood of success on lack of enablement based on the argument that the claims do not place any limitation on the proteins to be refolded and recite that the thiol-pair ratio is in the range of 0.001-100, resulting in a large number of possible redox conditions. Each of independent claims 1 and 16 recites “at least about 25% of the proteins are properly refolded,” and each of independent claims 10 and 26 recites “about 30–80% of the proteins are properly refolded.”
The claims also recite “wherein the thiol-pair buffer strength maintains the solubility of the preparation.” The Board was persuaded, at this stage, that this term may be indefinite because if the solubility is of the preparation itself and not that of proteins, it may be unclear which ingredients of the preparation are the solvent and which are the solute or how the thiol-pair buffer strength maintains such solubility. The Board, however, did not conclusively construe that claim term and noted the parties will fully develop the record during trial before resolving this dispute.
Accordingly, the Board granted institution on all grounds of the petition.
ModernaTX, Inc. v. CureVac AG, IPR2017-02194 (Final Written Decision Entered Apr. 16, 2019). The Board issued a final written decision on a patent challenged by ModernaTX, Inc., U.S. Patent No. 8,383,340 B2 (“’340 patent”), and assigned to CureVac AG, finding all claims (1–26) unpatentable. The patent at issue claimed a method for purifying RNA on a preparative scale by high-performance liquid chromatography (“HPLC”) using a porous reversed phase—namely, porous non-alkylated polystyrenedivinylbenzene (“PSDVB”)—as the stationary phase. ModernaTX asserted that certain claims are anticipated and all claims are obvious.
After denying both ModernaTX’s and CureVac’s motions to exclude, the Board determined that ModernaTX has shown by a preponderance of the evidence that all claims of the ’340 patent as challenged are unpatentable under 35 U.S.C. § 103(a) for obviousness as entailing an improvement that is no “more than the predictable use of prior art elements according to their established functions.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007).
Claim 1 is illustrative:
1. A method for purifying RNA on a preparative scale,
wherein the RNA is purified by HPLC or low or normal pressure liquid chromatography using a porous reversed phase as stationary phase and a mobile phase, wherein the porous reversed phase is a porous non-alkylated polystyrenedivinylbenzene.
ModernaTX explicitly premised its ground of unpatentability for anticipation on its view that the preamble is not limiting. Unfortunately for ModernaTX, the Board rejected its argument that the preamble is not limiting because it “does not result in a manipulative difference in the steps of the claim.” Because the Board held that the preamble is limiting, the ’340 patent was not anticipated. But ModernaTX prevailed in its obviousness challenge. The Board held that there was motivation to combine the asserted prior art references and an ordinarily skilled artisan would have had a reasonable expectation of success.
During the week of April 29–May 3, 2019, the Patent Trial and Appeal Board (“Board”) issued one decision in TC 1600—a final written decision in a post-grant review (“PGR”):
Grünenthal GmbH v. Antecip Bioventures II LLC, PGR2018-00001
Claims 1–2 were previously disclaimed. See PGR2018-00001, Paper 48 (Final Written Decision) at 3. Remaining claims 3–30 broadly embraced zoledronic acid in a salt or acid form, with or without the addition of one or more bioavailability-enhancing ingredients. See id. at 11. More specifically, the independent claims recited an oral pharmaceutical dosage form comprising forms of zoledronic acid and other components, including specific bioavailability percentages of zoledronic acid of about 1.2–4% in humans (claim 23), and a method for treating arthritis in humans comprising orally administering a zoledronic acid salt or acid dosage form and other components, also including specific bioavailability percentages of zoledronic acid of about 1.1–4% (claim 3). See id. at 5–7.
Petitioner Grünenthal GmbH asserted multiple grounds of unpatentability, including § 112(a) lack of enablement (claims 3–30), § 112(b) indefiniteness (claim 15), § 102 anticipation (claim 23), and multiple grounds of § 103 obviousness (claims 3–30). Id. at 7–8. However, the Board considered only § 112(a) lack of enablement of claims 3–30 before finding the claims unpatentable, and it declined to reach other grounds. Id. at 20–21. Specifically, under the Wands factors, the Board assessed whether the ’268 patent’s specification taught an ordinarily skilled artisan how to make and use any dosage form having zoledronic acid bioavailability within the claimed ranges:
- Wands factor one—the nature of the invention, level of skill in the art, and unpredictability of the art: Pharmaceutical formulations is an unpredictable field and bioavailability may be influenced by multiple factors. See id. at 11–12.
- Wands factor two—the state of the prior art: At least 22 forms of zoledronic acid and its salts were known before the priority date, were expected to have different properties, and were generally known to have poor bioavailability. An ordinarily skilled artisan would have believed that all zoledronic acid forms, as claimed, could not achieve a bioavailability above 1% without an enhancer. See id. at 12–13.
- Wands factor three—the breadth of the claims, lack of guidance, and absence of working examples: Claims 3–30 use the transitional phrase “comprising” and are “broad” claims, yet the specification disclosed (1) no examples of zoledronic acid dosage forms, (2) no bioavailability-enhancing ingredients that may be added to improve zoledronic acid’s bioavailability to at least 1.1%, and (3) no pharmacokinetic data identifying bioavailability of 1.1–4%. at 13–14. While the specification disclosed that the disodium salt form “may be more bioavailable,” the claims were not so limited. Id. at 14. Furthermore, the specification contained hypothetical bioavailability ranges without any “actual data obtained from any dosage form, or any other information explaining how to make a dosage form having a bioavailability that falls within the claimed ranges.” Id. at 14–15. In fact, the Patent Owner’s witness likened a belief that certain zoledronic acid salt forms might have bioavailability to within the range of 1.1% without enhancers to a “belie[f] in ‘fairies.’” Id. at 14.
- Wands factor four—the quantity of experimentation required: Patent Owner relied on a public reference, arguably within the skilled artisan’s knowledge, relating to bioavailability of a specific zoledronic acid salt form. The Board noted the reference’s failure to address bioavailability in humans (it addressed only beagle dogs), but ultimately focused on the need for enablement to be found in the specification, not in the knowledge of one skilled in the art. See id. at 15–17 (citing in part Genentech Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997)).
Ultimately, the Board found that 1) the field was unpredictable, 2) the claims were broad, 3) the specification lacked any “guideposts that would have illuminated a path toward even one dosage form that has a bioavailability that falls within the scope of any claim,” and 4) the level of experimentation required to determine whether even one dosage form falls within the scope of the claimed bioavailability ranges was far in excess of routine experimentation. See id. at 17–20. The Board thus found claims 3–30 unpatentable for lack of enablement.