Pharmacyclics LLC, Jannsen Biotech, Inc. v. Alvogen, Inc., Natco Pharma Limited
Docket No. 2021-2270 (https://cafc.uscourts.gov/opinions-orders/21-2270.OPINION.11-15-2022_2033497.pdf) (Non-Precedential)
CHEN, BRYSON, HUGHES
November 15, 2022
Brief Summary: DC decisions that Pharmacyclic’s patents were infringed and not invalid for lack of written description, enablement, obviousness, or obviousness-type double patenting affirmed.
Summary: Pharmacyclics and Jannsen (“Pharmacyclics”) appealed DC finding that Alvogen and Natco’s (“Alvogen’s”) ANDA to market a generic version of Pharmacyclic’s Bruton’s tyrosine kinase (BTK) inhibitor Imbruvica (ibrutinib) for cancer treatment infringed several Pharmacyclic patents. Pharmacyclic originally asserted many claims of 17 of its patents, but during the DC trial reduced the asserted claims to claim 10 of US 8,008,309 directed to the compound; claim 2 of US 8,754,090 directed to a method for treating mantle cell lymphoma; claim 5 of US 9,725,455 directed to a crystalline form of ibrutinib; and claims 30 and 37 of US 9,655,857 directed to tablet formulations of ibrutinib. At the DC, Alvogen stipulated it infringed the asserted claims of the ‘309, ‘090, and ‘455 patents, and the DC found it infringed the asserted claims of the ‘857 patent. The DC also rejected Alvogen’s invalidity arguments.
Regarding the ‘309 patent, Alvogen argued that Pharmacyclics’ provisional applications did not satisfy the written description (WD) or enablement requirements by failing to “disclose how to synthesize Intermediate 2” and was therefore anticipated by a prior art reference. But the DC found that the “bracketed citation” to a PCT publication of the provisionals would have led “[a]n artisan of ordinary skill” to undertsand “that the inventors cited [WO ’829] to explain how to synthesize Intermediate 2” used in the preparation of ibrutinib, or “could also have synthesized without the teachings” of the cited PCT “based on the structure of Intermediate 2 disclosed in the diagram…by working backwards from its structure to known starting compounds.” The FC panel found no error with the DC reliance on expert testimony and, further, “it is clear that Intermediate 2 was not novel because it was disclosed in the WO ’829 publication” and “Intermediate 2 was not a ‘novel aspect’ of claim 10 of the ’309 patent” (Genentech, FC 1997; Falko-Gunter, FC 2006 (“formal incorporation by reference is not necessary if the material being incorporated is background art”, “information readily accessible in journals need not be incorporated by reference in order to enable the patent claims at issue”)).
Regarding the ‘090 patent, Alvogen argued the method of treatment claims were not adequately described or enabled, obvious, or invalid for obviousness-type double patenting over Pharmacyclic’s ‘015 patent. The DC found the ‘090 specification made clear that the preferred BTK inhibitor was ibrutinib (WD and enablement), there was no motivation to combine the alleged obviousness references (e.g., “given the ‘unpredictable nature of oncology’”, no motivation “to use a once-daily dose or about 560 mg”, “safety concerns would have discouraged an artisan”). On double-patenting, the DC found, e.g., “the breadth of ranges…in the ‘015 patent weighed against applying the presumption of obviousness” and the 560 mg dose would not have been found by “routine experimentation”. The FC panel found the DC decision not to be clearly erroneous, and distinguished this case from its Biogen decision (FC 2021 (“claimed dosage of 480 mg was “listed only once”)) while here the 560 mg daily dose “is expressly recited by itself (rather than as part of a range”, “appears again in….Example 13”, and “the summary of the invention explicitly discloses a dose of ‘about 560 mg/day.’” The FC panel also found no clear error with the DC’s finding of no motivation to use 560 mg/day. The FC also found no clear error in the DC’s double-patenting decision since “a presumption of obviousness may be invoked ‘when the only difference from the prior art is a difference in the range or value of a particular variable’” (In re Kumar, FC 2005) and here “there are additional differences between the prior art and claim 2 of the ’090 patent” (e.g., “the prior art did not disclose that ibrutinib was effective at treating R/R MCL”).
Alvogen also argued claim 5 of the ‘455 patent directed to crystalline forms “was inherently anticipated” by a clinical study, but the DC concluded “a skilled artisan…would not have necessarily recognized” the “authors used crystalline Form A” (citing Endo, FC 2018). On obviousness of the ‘455 claim, the DC found none of Alvogen’s references “suggested that [Form A (‘with the claimed 2-Theta peaks’)] would be more desirable than any other crystalline form”, as well as Pharmacyclic’s secondary considerations of unexpected benefits and copying. The DC also disagreed with Alvogen’s invalidity arguments based on WD and enablement of the ‘857 claims (e.g., “recites verbatim the formulations” and dosages). The FC panel found no clear error with the DC’s conclusions (e.g., “[t]he question is what is “necessarily” inherent in the anticipating reference” (Schering, FC 2003); Endo (FC (“no evidence ‘that only one vehicle formulation—the claimed vehicle formulation” could be used to achieve the results of the clinical study’”); Grunenthal, FC 2019 (upholding a [DC’s] finding that a skilled artisan would not have expected success in producing a particular crystalline form of a compound when a skilled artisan would not have had ‘reason to know how the multiple variables involved in conducting a polymorph screen would affect the recrystallization’ of the compound”)).
Alvogen’s arguments that the ‘857 tablet claims were not supported by WD were also rejected by the DC. The FC panel found no clear error with that decision because, e.g., “the precise ranges recited in the claims are found in formulations disclosed in the specification”.