Ex Parte Remick et alDownload PDFPatent Trial and Appeal BoardDec 26, 201715135580 (P.T.A.B. Dec. 26, 2017) Copy Citation 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. 15/135,580 04/22/2016 David Michael Remick X20656 4306 25885 7590 12/28/2017 FT T T TT T Y fr TOMPANY EXAMINER PATENT DIVISION KAROL, JODY LYNN P.O. BOX 6288 INDIANAPOLIS, IN 46206-6288 ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 12/28/2017 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): patents @ lilly.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte DAVID MICHAEL REMICK, SIMON JAMES RICHARDS, and ADAM JAN SANDERSON Appeal 2017-009932 Application 15/135,5801 Technology Center 1600 Before ERIC. B. GRIMES, TIMOTHY G. MAJORS, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving selective BACE1 inhibitors. Spec. 1. The Examiner rejected the claims on appeal as obvious under 35 U.S.C. § 103(a). We reverse. 1 According to Appellants, the real party in interest is Eli Lilly and Company. App. Br. 1. Appeal 2017-009932 Application 15/135,580 STATEMENT OF THE CASE The Specification discloses: Alzheimer’s disease is characterized by the generation, aggregation, and deposition of Abeta [(amyloid P)] in the brain. Complete or partial inhibition of P-secretase (P-site amyloid precursor protein-cleaving enzyme; BACE) has been shown to have a significant effect on plaque-related and plaque- dependent pathologies in mouse models suggesting that even small reductions in Abeta peptide levels might result in a long term significant reduction in plaque burden and synaptic deficits, thus providing significant therapeutic benefits, particularly in the treatment of Alzheimer’s disease. Spec. 1. The Specification asserts that “[t]he present invention provides certain novel compounds that are inhibitors of BACE” and, more specifically, that are “selective inhibitors of BACE 1 over BACE2.” Id. at 2. The Specification discloses that these compounds can be used in a method of treating Alzheimer’s disease. Id. Claims 1—3, 7, 8, and 19 are on appeal. Claim 1 is illustrative and reads as follows: 1. A compound of the formula: F S F NH2 or a pharmaceutically acceptable salt thereof. App. Br. 13. 2 Appeal 2017-009932 Application 15/135,580 The Examiner rejected claims 1—3, 7, 8, and 19 under 35 U.S.C. § 103(a) as obvious over Suzuki.2 ANALYSIS In finding the pending claims obvious, the Examiner found that Suzuki disclosed compounds that inhibit production of Ap or BACE1 and are useful as prophylactic or therapeutic agents for treatment of neurodegenerative disease caused by Ap, as typified by Alzheimer-type dementia. Final Act.3 6. The Examiner further found that Example 280 of Suzuki disclosed the synthesis of N-[3-((4aS,5S,7aS)-2-amino-5- difluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [ 1,3]thiazin-7a-yl)-4- fluorophenyl]-5-dihydropyridine-2-carboxamide. Id. The compound of Example 280 differs from the claimed compound in that the claimed compound contains a methyl group substituted for the hydrogen in the difluoromethyl group as reflected in the below comparison. difluoromethyl group 1,1*difiuQro-1-efhyi group / \ | F h! F-O/ H position 5 n\~"7Ny $ A ..-A' H H F-V « v-h Compound 280 Elected Species from Suzuki ot aL Example 1 The above figure was included by Appellants in the Appeal Brief and provides a comparison of the compound of Example 280 of Suzuki to the compound disclosed in Example 1 of the Specification. App. Br. 9. 2 Suzuki et al., US Patent No. 8,158,620 B2, issued Apr. 17, 2012 (“Suzuki”). 3 Office Action mailed February 9, 2017 (“Final Act.”). 3 Appeal 2017-009932 Application 15/135,580 Based on the disclosure of compound 280, the Examiner concluded that “[i]t would have been obvious to one of ordinary skill in the art prior to the filing date of the invention to substitute the hydrogen of Compound 280 taught by Suzuki et al. with a methyl group to arrive at the instantly claimed compound.” Final Act. 7. The Examiner reasoned that “[i]t is well established that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results.” Id. (citing case law). The Examiner further reasoned that “the compounds of Suzuki et al. and the elected species of the instant invention would have been expected to have similar properties based on close structural and chemical similarity and the fact that both the prior art and the applicant used the compounds as BACE1 inhibitors.” Id. at 7—8, Appellants contend that Suzuki discloses a genus covering trillions of compounds and exemplifies 286 compounds falling within this genus. App. Br. 5. Appellants argue, inter alia, that neither the Examiner nor Suzuki provides reason to select compound 280 from among this large genus of compounds. Id. Appellants note that Suzuki provides IC50 data for 176 of the 286 exemplified compounds, but not for compound 280. Id. Appellants further note that Suzuki does not does not identify compound 280 as a preferred compound, highlight compound 280, or otherwise indicate that compound 280 provides any “benefit or special property” as compared to any of the other compounds disclosed. Id. Finally, Appellants note that no biological data is provided for compound 280. Id. Appellants thus assert that “one of ordinary skill in the art would have no reason to identify Compound 280 as a natural choice for further development efforts, and thus, a lead compound.” Id. 4 Appeal 2017-009932 Application 15/135,580 As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): “[T]he examiner bears the initial burden ... of presenting a prima facie case of unpatentability.” Appellants have persuaded us that the Examiner has not carried the burden of establishing that the claimed invention would have been obvious over the cited art. The Examiner relied on a lead compound analysis to find the claimed compound obvious. Final Act. 6—8; Ans. 6—10. A lead compound is defined as ‘“a compound in the prior art that would be most promising to modify in order to improve upon its . . . activity and obtain a compound with better activity.’” Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012) (citing Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007)). Stated another way, “a lead compound is ‘a natural choice for further development efforts.’” Id. (citing Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 1008 (Fed. Cir. 2009)). “While the lead compound analysis must, in keeping with KSR, not rigidly focus on the selection of a single, best lead compound,... the analysis still requires the challenger to demonstrate . . . that one of ordinary skill in the art would have had a reason to select a proposed lead compound or compounds over other compounds in the prior art.” Daiichi Sankyo Co., Ltd. v. Matrix Laboratories, Ltd., 619 F.3d 1346, 1354 (Fed. Cir. 2010). The analysis of whether a person of ordinary skill would have chosen the prior art compound as a lead compound “is guided by evidence of the compound’s pertinent properties” including “positive attributes such as activity and potency,” “adverse effects such as toxicity,” “and other relevant characteristics in evidence.” Otsuka, 678 F.3d at 1292. 5 Appeal 2017-009932 Application 15/135,580 Importantly, “[ajbsent a reason or motivation based on such prior art evidence, mere structural similarity between a prior art compound and the claimed compound does not inform the lead compound selection.” Id.', see also Daiichi, 619 F.3d at 1354 (“[Pjroving a reason to select a compound as a lead compound depends on more than just structural similarity, but also knowledge in the art of the functional properties and limitations of the prior art compounds.”). Suzuki discloses a genus of Ap and BACE1 inhibitory compounds encompassing, according to Appellants, trillions of compounds. App. Br. 5. Suzuki exemplifies 286 compounds falling within this broad genus. See, Suzuki col. 56,1. 5 — col. 428,1. 10. The Examiner, however, does not identity any teaching in the prior art that would have directed the skilled artisan to select compound 280 from among the many compounds disclosed and exemplified in Suzuki. Under Daiichi it is possible to have multiple lead compounds, but even considering only the compounds exemplified in Suzuki, it would not be reasonable to classify all 286 compounds as joint lead compounds. We are therefore persuaded by Appellants that the Examiner has not shown that a skilled artisan would have been led to treat compound 280 as a lead compound that would have been obvious to modify. Accordingly we reverse the Examiner’s rejection of claims 1—3, 7, 8, and 19 as obvious over Suzuki. DECISION For the reasons set forth herein, we reverse the Examiner’s rejection of claims 1—3, 7, 8, and 19 under 35 U.S.C. § 103(a) as obvious over Suzuki. REVERSED 6 Copy with citationCopy as parenthetical citation