IP Law Daily Patent for anti-cancer drug Zytiga was properly construed and found obvious
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Tuesday, May 14, 2019

Patent for anti-cancer drug Zytiga was properly construed and found obvious

By Peter Reap, J.D., LL.M.

Substantial evidence supported the conclusion that the asserted claims cover a therapy in which abiraterone has an anti-cancer effect and prednisone has either its own anti-cancer effect or a palliative/side-effect reduction effect. Substantial evidence also supported the finding that there was a reasonable expectation of success in combining the prior art to arrive at the invention.

In a dispute in which drug companies BTG International Limited et al. (Appellants) sued Amneal Pharmaceuticals LLC et al. (Appellees), asserting that Appellees’ Abbreviated New Drug Applications (ANDA) for the generic version of Appellants’ abiraterone product Zytiga infringes claims 1–20 (Asserted Claims) of U.S. Patent No. 8,822,438 (the ’438 patent), substantial evidence supported the Patent Trial and Appeal Board’s conclusion that the asserted claims cover a therapy in which abiraterone has an anti-cancer effect and prednisone has either its own anti-cancer effect or a palliative/side-effect reduction effect, the U.S. Court of Appeals for the Federal Circuit has decided. Moreover, substantial evidence supported the finding that there was a reasonable expectation of success in combining the prior art to arrive at the invention. Thus, the appellate court affirmed one of the three PTAB proceedings that had been consolidated with the Appellants’ suit, rendering the other appeals in the dispute moot (BTG International Limited v. Amneal Pharmaceuticals LLC, March 14, 2019, Wallach, E.).

After the Appellants filed their patent infringement suit, several drug companies filed three, separate inter partes review (IPR) petitions alleging that the Asserted Claims would have been obvious under 35 U.S.C. § 103 (2006). In all three IPRs, the PTAB issued claim construction orders adverse to Appellants, as well as final written decisions finding the Asserted Claims obvious. One of these proceedings is WockhardtWockhardt Bio AG v. Janssen Oncology, Inc., No. IPR2016-01582, 2018 WL 456328, at *21 (P.T.A.B. Jan. 17, 2018). Similarly, the federal district court in which Appellants filed their action concluded that the Asserted Claims would have been obvious in light of its claim construction and the same combination of prior art relied on by the PTAB. The Appellants appealed all of the PTAB’s final written decisions and the district court’s final judgment, and the appeals were consolidated.

The ‘438 patent. The ‘438 patent, entitled “Methods and Compositions for Treating Cancer,” teaches a method “compris[ing] administering a 17a-hydroxylase/C17,20-lyase [(‘CYP17’)] inhibitor, such as abiraterone acetate [(‘abiraterone’)] (i.e., β-acetoxy-17-(3-pyridyl)androsta-5,16-diene), in combination with at least one additional therapeutic agent such as an anti-cancer agent or a steroid.” Specifically, the ’438 patent discloses the administration of a therapeutically effective amount of a CYP17 inhibitor, such as abiraterone, with a therapeutically effective amount of at least one additional therapeutic anticancer agent. The ’438 patent defines an “anti-cancer agent” as “any therapeutic agent that directly or indirectly kills cancer cells or directly or indirectly prohibits[,] stops[,] or reduces the proliferation of cancer cells.” The ’438 patent lists acceptable forms of anti-cancer agents, including, inter alia, prednisone. Independent claim 1 is representative and recites: “[a] method for the treatment of a prostate cancer in a human comprising administering to said human a therapeutically effective amount of abiraterone acetate or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of prednisone.”

Prior art. Gerber, G.S. & Chodak, G.W., Prostate Specific Antigen for Assessing Response to Ketoconazole and Prednisone in Patients with Hormone Refractory Metastatic Prostate Cancer, 144 J. Urology 1177–79 (1990) (Gerber) is a study that evaluates prostate specific antigen (PSA) level changes. O’Donnell, A., et al., Hormonal Impact of the 17a-hydroxylase/C17,20-lyase Inhibitor Abiraterone Acetate (CB7630) in Patients with Prostate Cancer, 90 Brit. J. of Cancer 2317–25 (2004) (O’Donnell) is an article publishing the results of three clinical studies, and discloses the treatment of prostate cancer with abiraterone. Sartor, O., et al., Effect of Prednisone on Prostate-Specific Antigen in Patients with Hormone-Refractory Prostate Cancer, 52 Urology 252–56 (1998) (Sartor) evaluates the effects of prednisone on PSA levels in patients with hormone-refractory prostate cancer.

Arguments on appeal. Appellants asserted that the PTAB erred by (1) improperly construing the term “treatment” by not requiring prednisone to have an anti-cancer effect, and (2) relying on that incorrect construction to find that the Asserted Claims would have been obvious over a combination of Gerber, O’Donnell, and Sartor.

Claim construction. The PTAB in Wockhardt construed the Asserted Claims’ use of “treatment” as “includ[ing] the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the minimization or delay of the spread of cancer.” Appellants asserted that “[t]he [PTAB]’s decisions rest on an erroneous claim construction” because the term “‘treatment’ requires an anti-cancer effect.” The Federal Circuit did not agree.

The ’438 patent’s claims, specification, and prosecution history teach that “treatment” includes both anti-cancer effects and palliation or reduction in side effects of a different anti-cancer drug, according to the appellate court. Independent claim 1 of the ’438 patent discloses “a method for the treatment of a prostate cancer in a human comprising administering to said human a therapeutically effective amount of” prednisone, along with abiraterone. The specification defines a “therapeutically effective amount” of a “therapeutic agent” as an amount “effective for treating a disease or disorder . . . such as cancer.” Therefore, any definition of “treatment” must encompass the full range of the therapeutic agent’s effects disclosed in the specification. Prednisone is one such disclosed therapeutic agent, the court said.

The specification states that a “therapeutic agent” may be either “an anti-cancer agent or a steroid.” As such, the use of “or” in between “anti-cancer agent” and “steroid” suggests that a steroid is not necessarily the same thing as an anti-cancer agent, the court reasoned. Prednisone is similarly listed as an example of an antibiotic agent in the specification, which also states that antibiotic agents are one example of anti-cancer agents. Therefore, the specification explains that prednisone may be used as both a steroid and an anti-cancer agent. Further, because the specification explains that prednisone is an anti-cancer agent and a steroid, “treating” with prednisone must logically include more than just anti-cancer effects and should include the long-familiar steroid effects of palliation and reduction of side effects, the court explained. The prosecution history did not detract from, and if anything, supported the PTAB’s construction.

The PTAB, in light of intrinsic evidence and under the BRI standard, correctly construed “treatment” to mean “the eradication, removal, modification, management or control of a tumor or primary, regional, or metastatic cancer cells or tissue and the minimization or delay of the spread of cancer.” The claims do not specify that abiraterone and prednisone must have the same treatment effect. Thus, the PTAB correctly concluded that the Asserted Claims cover a therapy in which abiraterone has an anticancer effect, while prednisone either has its own anti-cancer effect or has a palliative/side-effect reduction effect, the Federal Circuit ruled.

Obviousness. In Wockhardt, the PTAB determined that the “prior art provides a reasonable expectation that prednisone could be used as a therapeutic agent in the treatment of prostate cancer.” Appellants asserted that the PTAB failed to find that a person having ordinary skill in the relevant art (PHOSITA) would have “reasonab[ly] expect[ed] . . . success in achieving the invention as claimed” by developing a combination therapy where both abiraterone and prednisone produce an anti-cancer effect in combination. The court disagreed.

Substantial evidence supported the PTAB’s finding that a PHOSITA would have a reasonable expectation of success in combining Gerber, O’Donnell, and Sartor to arrive at the invention of the Asserted Claims. Under the court’s claim construction, there is no requirement that prednisone must have an anti-cancer effect. Additionally, even under Appellants’ construction, the record showed that a PHOSITA would have a reasonable expectation of success in combining abiraterone and prednisone because they were both together and individually considered promising prostate cancer treatments at the time.

Based on Sartor, a PHOSITA would know that prednisone alone could treat prostate cancer, the court opined. Further, because Gerber teaches that it is safe and effective to treat prostate cancer with “the CYP17 inhibitor ketoconazole” in combination with prednisone and O’Donnell teaches that abiraterone is a more selective inhibitor of CYP17 than ketoconazole and effectively suppresses testosterone levels, a PHOSITA would have had a reasonable expectation of success in using prednisone, in combination with abiraterone, to treat prostate cancer. Because the appellate court concluded that the Asserted Claims are unpatentable as obvious, as the PTAB found in Wockhardt, it did not need to reach the remaining issues on appeal.

This case is No. 2019-1147.

Attorneys: Anthony C. Tridico (Finnegan, Henderson, Farabow, Garrett & Dunner, LLP) for BTG International Ltd. Constantine L. Trela, Jr. (Sidley Austin LLP) for Janssen Biotech, Inc., Janssen Oncology, Inc. and Janssen Research & Development, LLC. Charles B. Klein (Winston & Strawn LLP) for Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals of New York, LLC, Dr. Reddy's Laboratories, Inc. and Dr. Reddy's Laboratories, Ltd. Dennies Varughese (Sterne Kessler Goldstein & Fox, PLLC) for Wockhardt Bio AG.

Companies: BTG International Ltd.; Janssen Biotech, Inc.; Janssen Oncology, Inc.; Janssen Research & Development, LLC; Amneal Pharmaceuticals LLC; Amneal Pharmaceuticals of New York, LLC; Dr. Reddy's Laboratories, Inc.; Dr. Reddy's Laboratories, Ltd.; Wockhardt Bio AG; Par Pharmaceutical, Inc.; Par Pharmaceutical Companies, Inc.; Rising Pharmaceuticals, Inc.

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