Non-Prior Art Evidence Helps Sink Three Patents in IPR Proceeding
| October 18, 2018
Yeda Research and Development v. Mylan Pharmaceuticals Inc.
October 12, 2018
Before Reyna, Bryson and Stoll. Opinion by Reyna.
Summary
This precedential opinion highlights that use of non-prior art in an inter partes review (IPR) does not violate 35 U.S.C. § 311(b) (A petitioner in an inter partes review may request to cancel as unpatentable 1 or more claims of a patent only on a ground that could be raised under section 102 or 103 and only on the basis of prior art consisting of patents or printed publications.)
Background
Mylan filed petitions for IPR challenging all claims of three U.S. patents assigned to Yeda Research and Development Company (USPs 8,232,250, 8,399,413 and 8,969,302). The PTAB instituted review of all claims on two grounds: obviousness over Pinchasi in view of the FDA’s 1996 Summary Basis of Approval (SBOA), and obviousness over Pinchasi in view of Flechter. The PTAB concluded that the claims are unpatentable. Yeda appealed to the CAFC, asserting that its due process rights and the Administrative Procedure Act (APA) were violated because it did not have notice of, and an opportunity to respond to a non-prior art reference Khan 2009. Yeda also argues that the PTAB violated 35 U.S.C. § 311(b) by relying upon the non-prior art Khan 2009.
Discussion
The patents share a common specification claiming priority to two provisional applications, with an earliest priority date of August 20, 2009. The patents are directed to a treatment for relapsing-remitting multiple sclerosis (RRMS) using COPAXONE®[1] 40mg/mL (active ingredient: glatiramer acetate (GA). Side effects of GA injections include injection-site reactions (ISRs) which are physical symptoms at the injection site, and immediate post-injection reactions (IPIRs) which are reactions such as flushes, sweating, or palpitations.
A key limitation in the claims of the patents is administering a 40mg GA dose in three subcutaneous injections over seven days.
The prior art relied upon in the IPR proceeding along with results of a prior clinical trial presented a strong case of obviousness.
A first clinical trial using a 20 mg dose of GA was in 1987, followed by a TEVA Phase III clinical trial in 1995. A Phase III trial reviewer made recommendations for future researchers, asking “Is 20 mg the optimum dose? Are daily injections necessary?” In 1996, the FDA approved use of COPAXONE® 20mg/mL based on a daily injection of 20mg GA.
Pinchasi, published in 2007, discloses a 40 mg GA, every other day dosing regimen for the treatment of RRMS, noting improvement in efficacy which is not accompanied by a corresponding increase of adverse reactions which would have been expected upon doubling of the administered dose.
Flechter evaluated the treatment of RRMS with 20 mg administered every other day, noting that alternate day treatment is safe and well tolerated.
A 2009 study by Khan, published three weeks after the August 20, 2009 priority date, was introduced into the record as part of an expert declaration in response to Yeda’s patent owner’s response. In that response, Yeda had argued that a POSITA would have believed that more frequent than daily doses would have been the best way to enhance efficacy. The expert declaration had noted numerous prior art references suggested further investigation of less frequent dosing regimens. The expert concluded that Khan demonstrated that those of skill in the art were motivated to explore less frequent dosing.
Yeda believed that reliance upon Khan 2009 violated its due process rights, and was not proper under 35 U.S.C. § 311(b). With respect to due process, however, the introduction of new evidence during the course of a trial is expected and as long as the opposing party is given notice and an opportunity to respond, the introduction of such evidence is perfectly permissible under the APA. Yeda received notice of Khan 2009 and even deposed the expert after receiving the reply declaration with the Khan reference. Therefore, Yeda did have proper notice and an opportunity to respond to Khan 2009. In addition, the PTAB acknowledged that Khan 2009 was not prior art, but was probative of the fact that those of ordinary skill in the art were motivated to investigate dosing regimens of GA with fewer injections.
Yeda also contended that the PTAB improperly relied upon Khan 2009 in violation of 35 U.S.C. § 311(b). Thus, the CAFC examined whether the PTAB can consider non-prior art evidence in considering the knowledge, motivations, and expectations of a POSITA regarding the prior art. The answer is YES. The CAFC explained that the PTOs own regulations and prior decisions make clear that the PTAB can rely on evidence other than prior art. Section 312(a) (3) specifies that a petition should include both copies of patents and printed publications and affidavits or declarations of supporting evidence and opinions. The expert’s reliance on Khan 2009 is permissible as it supports and explains his position that a POSITA would have thought less frequent dosing worthy of investigation as of the priority date.
In regard to the conclusion of obviousness, Yeda argued that the PTAB erred as a matter of law in finding a reasonable expectation of success given that the pharmacokinetic and pharmacodynamics (pk/pd) profile, mechanism of action, optimal does and active species are all unknown, citing In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litigation, 676 F.3d 1063 (Fed. Cir. 2012). In Cyclobenzaprine, however, there were no prior clinical studies to suggest what would be a therapeutically effective formulation. The expectation of success need only be reasonable, not absolute. The substantial evidence supports the PTAB’s reliance on the clinical data and its conclusion that a POSITA would be motivated to combine Pinchasi’s 40 mg every other day dose with a less frequent dosing regimen such as 3 times per week, and would have a reasonable expectation of success.
Takeaway
Non-prior art can be used in an IPR proceeding as part of supporting evidence and opinions.
[1] COPAXONE® is licensed to Teva Pharmaceuticals, Inc. Teva reported in August that the drug had second-quarter sales of $464 million, a 46 percent drop from the $859 million it generated in the second quarter of 2017, which it attributed to Mylan’s launch. (Source: Law 360).
