Eli Lilly and Co. v. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, (PTAB October 22, 2015)

In an inter partes review (IPR) proceeding, the Patent Trial and Appeal Board (Board) found all of Los Angeles Biomedical Research Institute’s (LA-Bio Med) patent claims unpatentable on the basis of obviousness in view of a combination of published prior art. Eli Lilly and Co. v. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Cases IPR-2014-00752, Final Written Decision dated October 22, 2015 (Paper 44).

The patent at issue, U.S. Patent No. 8,133,903, relates to methods of treatment of fibrotic conditions, such as erectile dysfunction (ED), with phosphodiesterase inhibitors. Claim 1 of the ‘903 patent is directed to “a method comprising: a) administering a … (PDE 5) inhibitor according to a continuous long-term regimen to an individual with at least one of a penile tunical fibrosis and corporal tissue fibrosis; and b) arresting or regressing the … tissue fibrosis, wherein the PDE-5 inhibitor is administered at a dosage up to 1.5 mg/kg/day for not less than 45 days.” 

In 2013, LA-BioMed filed suit against Eli Lilly alleging the ’903 patent claims encompass the use of Lilly’s Cialis® (tadalafil) product for the once-daily treatment of ED. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center v. Eli Lilly and Co., No. 2:13-cv-08567 (C.D. Cal.)(stayed in view of IPR proceedings). Within the year, Eli Lilly submitted two IPR petitions challenging the validity of the ‘903 patent claims on the basis of anticipation and obviousness.

In the IPR proceeding addressing obviousness, the Board construed claim elements in dispute, including interpreting “continuous long-term regimen” as including administration of a drug over a period of time without intermission such that treatment is therapeutically effective, and not less that the claimed “up to 1.5 mg/kg/day 45 days” (although the later phrase was not defined)  (pages 6–7, 9). The Board did not adopt LA-BioMed’s position that the claim should be narrowed such that “continuous” required maintaining a constant level of PDE-5 inhibitor. The Board found “an individual . . . with fibrosis” to be one having symptoms, but not necessarily diagnosed with, fibrosis (page 8). The Board declined to interpret “arresting or regressing … the … fibrosis” because that is the intended result of administering the medication (pages 8–0).

Significantly, the Board concluded that LA-Bio Med was not entitled to claim priority to its earliest 2002 provisional patent application because the claim limitation of “up to 1.5 mg/kg/day” was not adequately disclosed by an animal study that could not confirm the exact dosage of drug delivered by daily water intake and could not be readily translated to a human dosage upper limit (pages 9–13). Consequently, the primary obviousness reference (Montorsi 2002) qualified as prior art against the ‘903 patent.

In evaluating obviousness, the Board concluded that Eli Lilly “demonstrated by a preponderance of the evidence that claims 1-5 of the ‘903 patent are unpatentable” in view of two prior publications (Montorsi 2002 and Porst 2000) and published patent application to Whitaker 2001 (page 2). As to claim 1, the Board found that Montorsi 2002 disclosed that the pathophysiology underlying ED can be fibrosis, and disclosed treatment of ED using up to daily doses of 100 mg of a PDE-5 inhibitor (sildenafil) over a 12-week to six-month period, one hour before sexual activity. Whitaker 2001 disclosed the motivation for the use of a long-term (eight to 12 weeks), up to daily treatment (rather than on-demand) for ED of one to 10 milligrams Viagra® (sildenafil, but preferably tadalafil). Porst 2000 provided further motivation for continuous dosing by disclosing the safety and efficacy of daily administration of another PDE-5 inhibitor (IC351) at up to 100 milligrams for three weeks to treat ED (pages 13–19). The Board agreed with Eli Lilly that a skilled artesian would have “had a reasonable expectation of success of achieving the claimed invention because Montorsi teaches early intervention, Whitaker teaches daily administration, and Porst teaches that the administration of 100 milligrams per day of a PDE-5 inhibitor was safe and generally well tolerated” (page 20). The Board did not find persuasive LA-Bio Med’s arguments relating to unexpected results in view of or teaching away by the prior art. The Board found claims 2-5 unpatentable for the same reasons and because no additional basis for patentability was presented (page 28). In December, LA-Bio Med filed a notice of appeal to the final decision on obviousness.

In the IPR proceeding addressing anticipation, Eli Lilly contended that the ‘903 patent claims 1-5 were unpatentable for being anticipated by Whitaker 2001 alone. However, the Board found that Whitaker did not disclose all of the elements of claim 1. Specifically, the Board concluded that Whitaker lacked a disclosure of daily administration of a PDE-5 inhibitor, even though the title of the Whitaker patent is “Daily treatment for the erectile dysfunction using a PDE5 inhibitor,” and discloses “…administration…preferably daily as long as the patient suffers from [ED]…”  The Board found Whitaker’s description of the clinical study assessing efficacy of a PDE-5 inhibitor for the treatment of ED wherein men took the study drug, “greater than 70 percent of the time during the study” (lasting eight to twelve weeks) to not inherently disclose daily dosing for at least 45 days, as claimed. Eli Lilly has filed a notice of appeal to the final decision on anticipation.