DSM IP ASSETS B.V.Download PDFPatent Trials and Appeals BoardAug 27, 202015697723 - (D) (P.T.A.B. Aug. 27, 2020) 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. 15/697,723 09/07/2017 Werner BONRATH BHD-4662-3503 4600 23117 7590 08/27/2020 NIXON & VANDERHYE, PC 901 NORTH GLEBE ROAD, 11TH FLOOR ARLINGTON, VA 22203 EXAMINER PATEL, SAGAR S ART UNIT PAPER NUMBER 1626 NOTIFICATION DATE DELIVERY MODE 08/27/2020 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): PTOMAIL@nixonvan.com pair_nixon@firsttofile.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte WERNER BONRATH, KUN PENG, LEI ZHANG, and ZHIBIN ZHU Appeal 2019-006507 Application 15/697,723 Technology Center 1600 ____________ Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and TAWEN CHANG, Administrative Patent Judges. JENKS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 files this appeal from Examiner’s decision to reject claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellant identifies the real party in interest as DSM IP Assets, BV. Br. 2. We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appeal 2019-006507 Application 15/697,723 2 STATEMENT OF THE CASE Claims 1–10 are on appeal, and can be found in the Claims Appendix of the Appeal Brief. Claim 1, is representative of the claims on appeal, and reads as follows: 1. A process for the preparation of a substituted imidazothiazolone compound of formula (I), or a stereoisomer thereof, or a stereoisomeric mixture thereof, which comprises: reacting a compound of formula (II), or a stereoisomer thereof, or a stereoisomeric mixture thereof, with a nucleophile in the presence of a fluoride-free Lewis acid to provide the compound of formula (I), or a stereoisomer thereof, or a stereoisomeric mixture thereof: wherein R is H, alkyl or alkylcarbonyl; R1 is benzyl; and R2 is alkyl group. Br. 14 (Claims Appendix). REJECTION Appellant requests review of Examiner’s rejection under 35 U.S.C. § 103 of claims 1–10 as obvious in view of US ’3282 and Schmitt.3 2 Chavan et al., US 6,486,328 B1, issued Nov. 26, 2002 (“US ’328”). 3 Schmitt and Reissig, Lewis Acid-Promoted Reactions of y-Lactols with Silyl Enol Ethers – Stereoselective Formation of Functionalized Tetrahydrofuran Derivatives, Eur. J. Org. Chem. 1169–74 (2001) (“Schmitt”). Appeal 2019-006507 Application 15/697,723 3 OBVIOUSNESS OVER US ’328 AND SCHMITT The issue in this rejection is whether the preponderance of evidence of record supports Examiner’s conclusion that the use of a fluoride-free Lewis acid is obvious in a reaction set out in US ’328, which uses silyl enol ether as a nucleophile. A. Findings of Fact (FF) FF1. Example 5 of US ’328 teaches the production of 6-Benzyl-7-(1- trimethylsilyloxy-2-oxocyclohexyl)-3-phenyl-(3S, 7R, 7aR)- perhydroimidazo[1,5-C][1,3]thiazole-5-one. US ’328, 6:30–57. The starting reactant was mixed with dichlorormethane and 1,2- bistrimethylsilyloxy cyclohexene, the Lewis acid boron trifluoride etherate (BF3Et2O) was added, and the reaction was stirred for 10 min at 0°C. Id. The product yield was 22%. Id. at 6:54. FF2. Examiner finds that the chemical compounds in the reaction described in Example 5 of US ’328 have the following structures: The figure shows the chemical structures of the reactants in US ’328 Example 5. Ans. 4. Examiner finds that the product of the reaction depicted above is encompassed by the claimed structure, wherein R is H, R1 is benzyl, and R2 is l-hydroxyl-2-oxocyclohexyl. Id. at 5. Appeal 2019-006507 Application 15/697,723 4 FF3. Example 6 of US ’328 teaches the production of 6-Benzyl-7-(1- trimethylsilyloxy-2-oxocyclohexyl)-3-phenyl-(3S, 7R, 7aR)- perhydroimidazo[1,5-C][1,3]thiazole-5-one. US ’328 6:60– 7:11. This is the same compound produced in Example 5. The starting reactant was mixed with dichlorormethane and 1,2- bistrimethylsilyloxy cyclohexene, followed by adding the Lewis acid boron trifluoride etherate (BF3Et2O), and then the reaction was stirred for 10 min at 10°C. Id. The product yield was 98%. Id. at 7:11. FF4. Schmitt teaches a Lewis acid promoted reaction with γ-lactols. Schmitt, Abstract. The phenyl-substituted γ-lactol gives a fairly high trans-selective reaction with silyl enol ether in the presence of zinc chloride as shown below in scheme 3: The figure above shows the chemical structures involved in the reaction of the phenyl-substituted γ-lactol (1b) with silyl enol ether in the presence of the Lewis acid ZnCl2. Schmitt 1170. The transformation of the silyl enol ether into substitution product using two different Lewis acids is shown below as scheme 4: Appeal 2019-006507 Application 15/697,723 5 The figure above shows the chemical structures involved in the reaction of a γ-lactol (1c) with silyl enol ether in the presence of the Lewis acid ZnCl2 or BF3Et2O. Id. Scheme 4 shows that “the diastereoselectivity of the γ-lactol reactions is independent of the Lewis acid employed. With BF3Et2O and with ZnC12 almost identical trans:cis ratios were observed, but the milder zinc Lewis acid [ZnCl2 with a product yield of 61%] afforded a considerably higher yield.” Id. B. Analysis Examiner finds that US ’328 teaches the preparation of a substituted imidazothiazolone compound of formula (I) of claim 1. Ans. 4; FF1–FF3. Examiner acknowledges that in US ’328 the reaction occurs “in the presence Appeal 2019-006507 Application 15/697,723 6 of [fluoride containing] Lewis acid, Boron trifluoride etherate, and the organic solvent, Dichloromethane.” Ans. 4; FF1–FF3. Examiner acknowledges that US ’328 does not disclose using a fluoride-free Lewis acid and achieving selectivity greater than 83% and higher as recited in claims 9 and 10, which depend from claim 1. Ans. 6. Examiner looks to Schmitt for teaching that “zinc chloride is the most suitable Lewis acid over boron trifluoride etherate and diethylaluminium chloride, when silyl enol ethers are employed as nucleophiles for the treatment of γ-lactols.” Ans. 8 (emphasis removed); FF4. Based on the combined teaching of US ’328 and Schmitt, Examiner concludes that it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to perform routine experimentation and incorporate the teachings of zinc chlorides [with silyl enol ethers as nucleophiles] as set forth by Schmitt with the process of using silyl enol ethers as nucleophiles as set forth by US ’328 in order to enhance the preparation method and increase the product yield of substituted imidazothiazolone compounds, with a reasonable expectation of success. Ans. 8. Upon consideration of the evidence on this record, and each of Appellant’s contentions, we find that the preponderance of evidence supports the Examiner’s conclusion that the subject matter of Appellant’s claims is unpatentable. Accordingly, we affirm Examiner’s rejections for the reasons set forth in the Answer and Final Action. We address Appellant’s contentions below. Appellant contends that there is a lack of reasonable expectation of success because the starting molecule acted on by the Lewis acid in US ’338 and Schmitt are structurally different. Br. 9. Appellant contends: Appeal 2019-006507 Application 15/697,723 7 Firstly, the compound of formula (II) employed in the process of the herein claimed invention [and disclosed in US ’328] is an imidazothiazolone compound having two rings whereas the γ- lactols employed in the process of the Schmitt et al publication have only one ring. Secondly, it will be observed that the compound of formula (II) employed in the process of the herein claimed invention has three heteroatoms, i.e., one oxygen atom (0) and two nitrogen atoms (N), while the γ-lactols employed in the process of the Schmitt et al publication have only one heteroatom (O). Br. 8. We are not persuaded by Appellant’s contention that the starting molecules in US ’328 and Schmitt are structurally so different that a skilled artisan would not have expected a silyl enol ether as a nucleophile in conjunction with a Lewis acid to react with the different starting molecules to produce the substituted product. Specifically, Appellant’s argument that because of the “substantial structural differences, a person ordinarily skilled in the art could not reasonably predict the success of the Lewis acid BF3•Et2O and ZnCl2 in the reaction of the compound of formula (II)” is unsupported attorney argument and, therefore, unpersuasive. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (explaining that arguments and conclusions unsupported by factual evidence carry no evidentiary weight). As Examiner explains, “the process of using fluoride-free Lewis acids with silyl enol ethers as nucleophiles is/would have been a commonly known technique to a person skilled in the art.” Ans. 11; FF4. We agree that the record supports Examiner’s position that when using silyl enol ethers as nucleophiles in conjunction with a Lewis acid in a reaction, the fluoride based (BF3Et2O) or fluoride-free (ZnCl2) Lewis acids are interchangeable as specifically taught by Schmitt. See FF4. Appellant did not provide objective Appeal 2019-006507 Application 15/697,723 8 evidence that it would have been unpredictable that Schmitt’s Lewis acid would work in the reaction described in US ’328, particularly when the underlying nucleophile chemistry is the same in both reactions. Furthermore, “[o]bviousness does not require absolute predictability of success. . . . For obviousness under § 103, all that is required is a reasonable expectation of success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988). Appellant contends that it was surprising to achieve such high yield in the presence of fluoride-free Lewis acid. Br. 12 (The method “provides unexpectedly higher yield4 of the compound of formula (I) as compared to the processes as disclosed in US ’328 and Schmitt et al. For example, when the Lewis acid ZnCl2 is used, the yield is 91 % of the compound 3.”). We agree with Examiner that Appellant’s contentions with respect to high yield is not persuasive. As Examiner explains, in US ’328 examples 5 and 6 disclose the production of compound of formula (I). See Ans. 12; FF1, FF3. The same compound is produced in both examples. While the reactants are the same, the reaction temperature is different between these two examples. Compare FF1 with FF3. As Examiner points out example 6 has product yield of 98%. Ans.12. This increase in product yield is achieved by raising the reaction condition by 10°C. FF1. Compare FF1 with FF3. In addition, Examiner explains that “Schmitt teaches that ZnCl2 afforded a considerably higher yield as a Lewis acid over boron trifluoride etherate, BF3•Et2O, and diethylaluminium chloride.” Ans. 12; FF4. Schmitt shows 4 Appellant argues “high yield,” which is different from “high selectivity.” See Spec. 6, table 1. Based on the disclosure in the Specification, we interpret “high yield” to be the amount of product (formula (I)) made as opposed to any by-product. Appeal 2019-006507 Application 15/697,723 9 that the product yield using BF3•Et2O is 20% while substituting ZnCl2 in the same reaction results in a product yield of 61%. FF4. Based on the advantages of ZnCl2 as a Lewis acid as taught in Schmitt we agree with Examiner that that there is ample motivation to substitute ZnCl2 as the Lewis acid in the reaction as taught in US ’328 with an expectation of achieving a high yield. Examiner’s position is that through performing routine experimentation there would have been a reasonable expectation to achieve higher product yields. See Ans. 12. We agree that the record supports the position that changing either the temperature of the reaction or the Lewis acid are ways to increase product yield. FF1, FF3, FF4. Picking one of a finite number of known solutions to a known problem is obvious. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). For the foregoing reasons we affirm Examiner’s obviousness rejections. C. Conclusion We conclude that the evidence cited by Examiner supports a prima facie case of obviousness with respect to claim 1, and Appellant has not provided persuasive evidence to rebut the prima facie case. As Appellant does not argue the claims separately, claims 2–10 fall with claim 1. 37 C.F.R. § 41.37 (c)(1)(iv). Appeal 2019-006507 Application 15/697,723 10 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1–10 103 US ’328, Schmitt 1–10 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED Copy with citationCopy as parenthetical citation