Ex Parte Friedlander et al

Patent Trial and Appeal BoardMar 10, 2014

11884957 (P.T.A.B. Mar. 10, 2014)

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. 11/884,957 08/23/2007 Martin Friedlander TSRI 1104.1 8499 2387 7590 03/10/2014 Olson & Cepuritis, LTD. 20 NORTH WACKER DRIVE 36TH FLOOR CHICAGO, IL 60606 EXAMINER WANG, CHANG YU ART UNIT PAPER NUMBER 1649 MAIL DATE DELIVERY MODE 03/10/2014 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte MARTIN FRIEDLANDER, EYAL BANIN, and EDITH AGUILAR __________ Appeal 2012-007949 Application 11/884,957 Technology Center 1600 __________ Before LORA M. GREEN, MELANIE L. McCOLLUM, and ANNETTE R. REIMERS, Administrative Patent Judges. GREEN, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal1 under 35 U.S.C. § 134 from the Examiner’s rejection of claims 1 and 2.2 We have jurisdiction under 35 U.S.C. § 6(b). 1 The application is owned by The Scripps Research Institute and licensed to Merck KgaA (App. Br. 1). 2 Claims 3-5 are also pending, but stand withdrawn from consideration (App. Br. 1, Ans. 3). Appeal 2012-007949 Application 11/884,957 2 STATEMENT OF THE CASE Claim 1 is the only independent claim on appeal, and reads as follows: 1. A method for reducing neovascularization and promoting revascularization of ischemic retinal tissue damaged by exposure to a high oxygen level, the method comprising administering to the retina of a mammal suffering from oxygen-induced retinal ischemia, just after return to normoxia, a therapeutically effective amount of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) sufficient to inhibit pathological neovascularization and to promote physiological revascularization of the ischemic areas of the retina, wherein the fragment of TrpRS is selected from the group consisting of T2-TrpRS (SEQ ID NO: 1), T2-TrpRS-GD (SEQ ID N9; 2), mini- TrpRS (SEQ ID NO: 3), and Tl-TrpRS (SEQ ID NO: 4). The following ground of rejection is before us for review: Claims 1 and 2 stand rejected under 35 U.S.C. § 103(a) as being rendered obvious by the combination of Schimmel3 and Gole4 (Ans. 6) We reverse. ANALYSIS The Examiner relies on Schimmel for teaching “a method for treating neovascular eye diseases such as age-related macular degeneration, retinopathy of prematurity, ischemic retinopathy by using truncated tryptophanyl-tRNA synthetase (TrpRS) derived polypeptides including T2- TrpRS (SEQ ID NO:1) as recited in instant claims 1-2” (Ans. 6). The Examiner finds that Schimmel teaches: 3 Schimmel et al., WO 02/067970 A1, Sep. 6, 2002. 4 Gole et al, The mouse model of oxygen-induced retinopathy: A suitable animal model for angiogenesis research. 74 DOCUMENTA OPHTHALMOLOGICA, 163-169 (1990). Appeal 2012-007949 Application 11/884,957 3 [A] method of evaluating the therapeutic efficacy of potential therapeutic agents for treating neovascular diseases in an animal model comprising exposing a neonatal mouse to a hyperoxic (i.e. high oxygen level) condition and administrating TrpRS derived polypeptides including T2-TrpRS (SEQ ID NO:1) to the test animals, and evaluating the effects of the polypeptides on retinal vasculature of the animals (see p. 47-48, p. 51-53, in particular, based on the page number listed at the bottom of the reference). (Id. at 7.) The Examiner finds that although Schimmel does not specifically teach that T2-TrpRS promotes revascularization, that result would be inherent in its administration to the retina of patients “with age-related macular degeneration, retinopathy of prematurity, ischemic retinopathy” (id.). The Examiner notes that Schimmel “does not teach ‘administration of TrpRS to the retina, just after return to normoxia’ as recited in instant claim 1” (id. at 8). The Examiner relies on Gole for its teaching “that oxygen-induced retinopathy caused by a high level of oxygen is an appropriate animal model for retinopathy of prematurity” (id.). Specifically, the Examiner finds that Gole teaches that “newborn mice exposed to high (>98%) ambient oxygen during the newborn period and subsequently removed to room air (i.e. normoxia) will develop a proliferative retinopathy, which mimics the neovascular component of acute retinopathy of prematurity” (id.). The Examiner thus finds that “Gole indicates that exposure to a high oxygen level and return to normoxia can induce oxygen-induced retinal ischemia” (id. at 8-9). The Examiner finds also that Gole supports the “the condition of exposure to a high oxygen level and then returning to normoxia mimics Appeal 2012-007949 Application 11/884,957 4 the neovascular components in retinopathy of prematurity and ischemic retinopathy as taught by [Schimmel]” (id. at 9). The Examiner concludes that it would have been obvious to the ordinary artisan at the time of the invention to administer a therapeutically effective amount of TrpRS to the retina of an animal suffering from oxygen- induced retinal ischemia, just after return to normoxia (id.). According to the Examiner: The person of ordinary skill in the art would have been motivated to do so with an expectation of success because the exposure to a high oxygen level and then return to normoxia induces retinal ischemia; and such a condition or damage also happens in patients with retinopathy of prematurity. Thus, the person of ordinary skill in the art would have been motivated to administer T2-TrpRS (SEQ ID NO:1) to the retina of the mammal suffering from oxygen-induced retinal ischemia, just after return to normoxia by the combined teachings of W002/067970 (Schimmel et al.) and Gole et al. to avoid or to reduce the damage caused by oxygen-induced retinal ischemia, or to avoid or reduce further damage or retinal ischemia damage caused by the oxygen change from high oxygen to normoxia. (Id.) Appellants argue that the Examiner erred in relying on Schimmel in rejecting the claims, as the ordinary artisan would have not considered Schimmel “when considering the present invention” (Reply Br. 1). Specifically, Appellants argue that Schimmel “teaches only reduction or inhibition of ocular neovascularization in mammals” (Reply Br. 1). Appellants assert that while Schimmel teaches the use of T2-TrpRS, it only teaches that it is effective in blocking VEGF-induced neovascularization, but Appeal 2012-007949 Application 11/884,957 5 there is no mention of oxygen-induced retinal ischemia, or the administration of T2-TrpRS after return to normoxia (id. at 1-2). Appellants argue further that Gole is silent “about when oxygen- induced retinal blood vessel proliferation begins’” (App. Br. 4). Appellants note that in Gole, newborn mice were exposed to 100% oxygen for five days, returned to normal oxygen levels on the sixth day, and euthanized on the tenth day (id. at 5). Retinas were only examined after euthanization, and thus the onset of retinal proliferation could have occurred at any time during the ten days (id.). Thus, Appellants assert, the ordinary artisan “would not have placed any particular significance on the time of return to normoxia” (id.). We agree with Appellants that the Examiner has not made a prima facie case, based on the combined teachings of Schimmel and Gole, that the ordinary artisan would have found it obvious to administer to the retina of a mammal suffering from oxygen-induced retinal ischemia, just after return to normoxia, a therapeutically effective amount of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS). Schimmel teaches that the “[p]roliferation of new blood vessels in response to a variety of stimuli occurs as the dominant finding in the majority of eye disease and that blind including proliferative diabetic retinopathy (PDR), ARMD, rubeotic glaucoma, interstitial keratitis and retinopathy of prematurity” (Schimmel, 75). 5 The page numbers refer to the page numbers found at the bottom of the reference. Appeal 2012-007949 Application 11/884,957 6 Schimmel teaches further that TrpRS has potent angiostatic effect for retinal angiogenesis (Schimmel, p. 46). Schimmel teaches that neonatal mice were injected intra-vitreally with TrpRS 7 or 8 days postnatal, and euthanized 12 days postnatal (id. at 47). Most of the eyes treated with a control exhibited normal retinal vascular development, but complete inhibition of the outer vascular network was seen in 28% of the eyes treated with TrpRS (id. at 48). According to Schimmel, the inhibition is specific for newly developing vessels (id. at 52). The Examiner does not explain, however, how Schimmel exposes the neonatal mouse to a hyperoxic environment. Gole teaches that newborn mice that are exposed to high ambient oxygen during the newborn period, and then removed to ambient air, “develop a proliferative retinopathy which mimics the neovascular component of acute retinopathy of prematurity” (Gole, Abstract). Gole teaches that because the mouse model mimics the proliferative phase of retinopathy of prematurity, it would be “a suitable model for research aimed at controlling the proliferative phases of [retinopathy of prematurity] and other proliferative retinopathies” (id. at 167). As to the administration of a potential therapy, Gole teaches only that the “prevention of blindness from [retinopathy of prematurity] must . . . be aimed at preventing retinal detachment from occurring, so therapy must be applied during or before the proliferative phase of the disease” (id.). While the Examiner concludes that it would have been obvious to administer a therapeutically effective amount of TrpRS to the retina of an animal suffering from oxygen-induced retinal ischemia, just after return to Appeal 2012-007949 Application 11/884,957 7 normoxia, the Examiner points to no teaching in either Schimmel or Gole, or provides any scientific reasoning, as to why that would be an obvious time to administer the TrpRS. Rather, the Examiner merely provides the conclusory statement that it would avoid or reduce further damage or retinal ischemia damage caused by the oxygen change from high oxygen to normoxia (Ans. 9). “Rejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006), cited with approval in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007). We, therefore, reverse the rejection of claims 1 and 2 under 35 U.S.C. § 103(a) over the combination of Schimmel and Gole. REVERSED lp