THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

Patent Trials and Appeals BoardAug 26, 2020

2020001340 (P.T.A.B. Aug. 26, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 15/527,103 05/16/2017 Anantha Harijith UIC0050US.NP 2718 26259 7590 08/26/2020 LICATA & TYRRELL P.C. 66 E. MAIN STREET MARLTON, NJ 08053 EXAMINER FAY, ZOHREH A ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 08/26/2020 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): PTOactions@licataandtyrrell.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ANANTHA HARIJITH, VISWANATHAN NATARAJAN, ROBERTO F. MACHADO, and JEFFREY JACOBSON __________ Appeal 2020-001340 Application1 15/527,103 Technology Center 1600 __________ Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method of treating a pulmonary disease or condition, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. STATEMENT OF THE CASE Appellant’s Specification indicates that there is a known “correlation between sphingosine kinase (SphK) activity and lung injury.” (Spec. ¶ 4.) For example “increased expression of sphingosine kinase 1 (SphKl) has 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as The Board of Trustees of the University of Illinois. (Appeal Br. 1.) Appeal 2020-001340 Application 15/527,103 2 been found in lung tissues from patients with idiopathic pulmonary fibrosis.” (Id.) The Specification also states that selective inhibitors of SphK1 are known in the prior art. (Id. ¶ 5.) Appellant’s invention is directed at treating pulmonary diseases or conditions with a selective SphK1 inhibitor having 20-fold greater selectivity for SphK1 than SphK2 and a 50% inhibition at less than 10 μM. (Id. ¶6.) Claims 1–5 and 11–13 are on appeal.2 Claim 1 is illustrative and reads as follows: 1. A method of treating a pulmonary disease or condition in a subject comprising administering to a subject in need of treatment an effective amount of a SphKl inhibitor to treat the subject’s pulmonary disease or condition, wherein the SphKl inhibitor (a) exhibits at least a 20-fold greater selectivity for SphKl than SphK2; and (b) is cell permeable, has an IC50 value of less than 10 μM, or has a Ki of less than 10 μM, or a combination thereof. (Appeal Br. 16.) 2 Claims 6–8 remain pending, but are withdrawn from consideration. Appeal 2020-001340 Application 15/527,103 3 The prior art relied upon by the Examiner is: Name Reference Date Santos et al. WO2013/119946 A1 Aug. 15, 2013 Mark E. Schnute et al., Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1, 444 Biochem J., 79– 88 (2012). The following ground of rejection by the Examiner is before us on review: Claims 1–5 and 11–13 under 35 U.S.C. § 103(a) as unpatentable over Santos and Schnute. DISCUSSION The Examiner finds that Santos teaches administering “an effective amount of a SphK1 inhibitor to prevent or treat [a] subject’s pulmonary disease or condition.” (Final Action 6.) The Examiner further finds that Santos teaches “the SphK1 inhibitor is cell permeable and has a . . . [Ki] of less than 10 μm (para [0130[]]), Table 2, pg 46, Compound 64, . . . Compound 64 of the invention is a potent and selective Inhibitor of SphK1).” (Id.) The Examiner finds that Santos does not teach the SphK1 inhibitor to be PF-543 (the compound recited in claims 3 and 11). (Id.) The Examiner concludes, however, that substituting Compound 64 of Santos with PF-543 would have been obvious in light of the teachings of Schnute. (Id. at 6–7.) In particular, the Examiner finds that Schnute teaches PF-543 is “a potent and selective inhibitor of SphK1 activity” and as such substitution of PF-543 for Compound 64 would have been obvious “to enhance the efficacy of inhibiting SphK1 activity and to thereby improve therapeutic efficacy of treating a pulmonary disease in a subject.” (Id.) Appeal 2020-001340 Application 15/527,103 4 We disagree with the Examiner’s factual findings and conclusion that the claims are obvious over Santos and Schnute. In particular, we disagree that Santos teaches treating a pulmonary disease or condition with a selective SphK1 inhibitor. As Appellant notes, Santos is directed to using compounds of formula 1 for treating a myriad of diseases or conditions. (See Appeal Br. 12; Reply Br. 2; Santos ¶¶ 15, 36, 37.) Those conditions include neoplastic diseases (Santos ¶ 39), diseases that involves excess vascular growth, such as macular degeneration (id. ¶ 40), inflammatory diseases (id. ¶¶ 42–43), allergic diseases (id. ¶ 41), sepsis (id. ¶ 46), as well as fibrotic diseases, such as pulmonary fibrosis (id. ¶ 45). Compounds of formula I are required to be SphK enzyme inhibitors, but not necessarily selective SphK1 inhibitors as required by the claims. They may “have activity as selective inhibitors of the SphKl enzyme or the SphK2 enzyme or have activity as inhibitors of both SphKl and SphK2 enzymes.” (Santos ¶ 37.) It is true that Santos teaches Compound 64 selectively inhibits SphK1, decreasing S1P. (Id. ¶¶ 130 Table 2, 575.) However, Santos teaches a number of other compounds for use in treating any one of the identified diseases or conditions including, as Appellant explained, compound SLR080811 (Appeal Br. 12), which is an SphK2-selective inhibitor and increases S1P levels. (Santos ¶¶ 573–574, ¶ 57 (noting “compound (S)-2-(3- (4-octylphenyl)-1,2,4-oxadiazol-5-YL)pyrrolidine-1-carboximidamide (SLR080811)”); ¶ 130 Table 2 (noting compound (S)-2-(3-(4-octylphenyl)- 1,2,4-oxadiazol-5-YL)pyrrolidine-1-carboximidamide is compound 49).) Furthermore, Santos links pulmonary fibrosis treatment and compounds of Formula 1 that have activity to “improve the barrier function Appeal 2020-001340 Application 15/527,103 5 of endothelial cells, which are identified as compounds “of Formula 1 that inhibit[] SphK2 enzymatic activity.” (Id. ¶ 48.) The Examiner did not identify disclosure in Santos that ties the use of a selective inhibitor of the SphKl enzyme as opposed to a selective inhibitor of the SphK2 enzyme for treating a pulmonary condition. Thus, we do not agree with the Examiner that Santos teaches the use of compound 64, which is an SphK1 selective inhibitor, for use in treating pulmonary disease. Instead, we find the Examiner’s position that Santos teaches compound 64 for treating a pulmonary condition amounts to an impermissible application of obvious to try. Nothing in Santos that we have been guided to indicates that SphK1 inhibition is critical for treating pulmonary conditions or provides any suggestion that compound 64 would be likely to be successful in treating pulmonary conditions as opposed to one of the other myriad conditions mentioned. In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009) (identifying two categories of obvious-to-try situations that do not equate to prima facie obviousness under § 103: when what was “obvious to try” was (a) to vary all parameters or try every available option until one succeeds, where the prior art gave no indication of critical parameters and no direction as to which of many possibilities is likely to be successful; or (b) to explore a new technology or general approach in a seemingly promising field of experimentation, where the prior art gave only general guidance as to the particular form or method of achieving the claimed invention.). We also agree with Appellant that the Examiner has not adequately established a reason that it would have been obvious to substitute PF-543 for compound 64 to treat a pulmonary condition. (Appeal Br. 12–13; Reply Br. Appeal 2020-001340 Application 15/527,103 6 3.) Schnute determines “PF-543 is the most potent inhibitor of SphK1 described to date.” (Schnute Abs.) However, the Examiner did not identify any teaching in Schnute to tie this fact to a reasonable expectation that this compound would be able to treat pulmonary conditions. Schnute does not attribute any treatment capabilities with this compound, despite recognizing that inhibitors of SphKl could potentially lead to the development of novel strategies for the treatment of autoimmune diseases, for cancer therapy and for neurodegenerative diseases. (Id. at 85.) In fact, Schnute notes, with regard to the cancer cell line 1483 in which the compound was tested, that despite inhibiting SphK1 to a great extent, the cancer cell line grew at the normal rate. (Id. at 87.) Schnute also was also “unable to confirm growth inhibition by blockade of SphKl activity in U937 [leukemia] and LN229 [glioblastoma] cells.” (Id.) After performing various experiments, Schnute concludes only that PF-543 “provides a new and valuable tool for the interrogation of biological effects of modulation of S1P signaling resulting from specific inhibition of SphK 1 catalytic activity.” (Id. at 87.) For the foregoing reasons, we do not affirm the Examiner’s rejection of claims 1–5 and 11–13 as being obvious from Santos and Schnute. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1–5, 11–13 103 Santos, Schnute 1–5, 11–13 REVERSED