Los Angeles Biomedical Res. Inst. (“LAB”) V. Eli Lilly and Company

Docket No. 2016-1518 (IPR2014-00752)

February 28, 2017

Brief Summary: Board conclusion of obviousness vacated and remanded for determination of whether there was an “apparent reason to combine the prior art references” in view of correct claim construction.

Summary: LAB appealed Board IPR holding that US 8,133,903 relating to “a method of ‘arresting or regressing’ a condition known as penile fibrosis” (a form of erectile dysfunction) using “up to 1.5 mg/kg/day” of a “cyclic guanosine 3’,5’-monophosphate (cGMP) type 5 phosphodiesterase (PDE5) inhibitor…for not less than 45 days” is unpatentable as obvious. “[T]he ‘903 patent explains…that the use of PDE5 inhibitors was ‘not addressed to the long-term cure of underlying tissue fibrosis’” (“[T]here was ‘[n]o effective method of treatment…directed towards the molecular pathways underlying excessive collagen deposition’ to address penile fibrosis.”) This dispute began when LAB filed an infringement action against Lilly with respect to Cialis (tadalafil) (sildenafil (Viagra) is also a PDE5 inhibitor but not at issue here). Lilly then filed multiple IPRs againt the ‘903 patent (IPR2014-00693 in which the Board found no anticipation, affirmed by FC 2/28/17), alleging obviousness in view of three references (Montorsi, Whitaker and Porst). The Board construed “an individual with at least one of penile tunical fibrosis and corporal tissue fibrosis” as “an individual hav[ing] symptoms that may be associated with penile fibrosis…but not…specifically diagnosed as having penile tunical fibrosis [PTF] and corporal tissue fibrosis [CTF]”, “‘arresting or regressing the at least one of the” PTF and CTF “as having no limiting role, but merely stating an intended result”, and “continuous long-term regimen” as “the administration of drug over a certain period of time without intermission such that the treatment is therapeutically effective.” It also concluded LAB’s provisional application did not disclose the claimed dosage limitation and denied its argument for that priority date. Regarding the combination of references and obviousness, the Board found that Montorsi and Whitaker taught administering a PDE5 inhibitor and Porst disclosed “safe and well tolerated” administration of 100 mg tadalafil (Cialis) daily for three weeks to men with erectile dysfunction. The Board rejected LAB’s unexpected results arguments because the claims “do not require a particular mechanism of action and that any antifibrotic effect…whether expected or not, is inherent.” It “concluded that the combination of references satisfies each of the limitations of the ‘903 patent, as construed, and that the combination provides a reasonable expectation of success”.

The FC panel agreed with the Board on the priority date issue as the provisional “does not explicitly disclose” the claimed dosage. LAB argued the skilled artisan “would be able to calculate the corresponding human dosage” from the rat study disclosed in the provisional “according to a conversion method” of a “reference that was not disclosed in the provisional application, is nearly a half century old, and was based on measurements of toxicity of anticancer agents” (characterized that way by the FC panel), but the Board and the FC disagreed (“[T]his first four variables were not knowable from the disclosure…at best require persons of skill to look to the prior art and make assumptions…That is not enough to establish priority…proof of priority requires written description disclosure in the parent application, not simply information and inferences drawn from uncited references” (Lockwood, FC 1997; Allergan, FC 2015 (“‘[I]t is the disclosure of the [provisional] application[] that count,’ not those of uncited references.”)).

The FC panel disagreed with the Board’s construction of “an individual hav[ing] symptoms that may be associated with penile fibrosis…but not…specifically diagnosed as having” PTF or CTF, finding it “overly broad” (“would make the patent claims applicable to individuals without penile fibrosis”) under Cuozzo (BRI) and citing Rapoport (FC, 2001 (“treatment of sleep apneas” found not to encompass treatment of symptoms associated with sleep apnea)). The FC panel also concluded “arresting or regressing” “is more than a statement of the intended result” as “the phrase…is drafted as part of a separate step of the method, not as the preamble or introduction to a process carried out by administration of the drug” (distinguishing it from Bristol-Myers (FC 2001) (regarding the preamble phrase “for reducing hematologic toxicitiy”) and In re Montgomery (FC 2012)) and “adds an efficacy requirement that is not otherwise found in the claim language.” LAB unsuccessfully argued that “‘continuous long-term regimen’ adds a requirement that the drug concentration…attain a ‘constant level’” but the the FC panel disagreed since, e.g., the passage relied upon “does not exclude any treatment that fails to maintain an unvarying level of the drug within the patient’s body” and “[t]he prosecution history undercuts LAB’s argument” as claim 16 of the provisional application “required both a ‘continuous long term regimen’ and ‘maintaining a constant level’” but the ‘903 claims did not. The FC panel also agreed with the Board’s construction of the term.

The FC panel agreed with LAB, however, that “the Board’s findings are insufficient to establish obviousness under the correct constructions of” the PTF/CTF and “arresting or regressing” limitations (e.g., “Whitaker makes that the observation about ‘vascular conditioning’ and its cause is speculative” and cannot therefore “serve as an express or implicit teaching” (Star Scientific, FC 2011 (“speculative and tentative disclosure”); Alza, FC 2006 (obviousness determinations “should be based on evidence rather than on mere speculation or conjecture”)). It also found “the Board summarily dismissed LAB’s counterargument” that the references “would not have given rise to a reasonable expectation of success in treating erectile dysfunction in the subpopulation suffering from penile fibrosis”. Thus, it remanded the decision “for the Board to make new findings as to whether there was an apparent reason to combine the prior art references and whether that combination would have rendered obvious the long-term administration of PDE5 inhibitors to treat penile fibrosis.”

Judge Newman dissented, while not “diminish[ing] the scientific value” of the inventors’ work, because the Board’s decision was based on substantial evidence and “accords with precedent” (Bristol-Myers, FC 2001 (“[n]ewly discovered results of not processes directed to the same purpose are not patentable because such results are inherent”); Alcon, FC 2012 (specific high concentrations obvious to try); Allergan, FC 2013 (enhanced efficacy by “reducing the number of daily ophthalmic doses” not taught or inherent in prior art); Rapoport, FC 2001 (treating sleep apnea not inherent in prior art disclosure of treating anxiety). Judge Newman wrote that the difference from Allergan and Rapoport is that “[h]ere…penile fibrosis was known in the prior art to be a mechanism of causing erectile dysfunction”.

This entry was posted in Anticipation (35 USC 102), Claim Construction, Inter Parties Review (IPR), IPR, Obviousness, Priority. Bookmark the permalink.

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