Ex Parte Jaekel et alDownload PDFPatent Trial and Appeal BoardDec 19, 201612307472 (P.T.A.B. Dec. 19, 2016) 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. 12/307,472 01/05/2009 Christoph Jaekel 336162US0PCT 3317 22850 7590 12/21/2016 OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P. 1940 DUKE STREET ALEXANDRIA, VA 22314 EXAMINER SAWYER, JENNIFER C ART UNIT PAPER NUMBER 1671 NOTIFICATION DATE DELIVERY MODE 12/21/2016 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): patentdocket @ oblon. com oblonpat @ oblon. com ahudgens@oblon.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CHRISTOPHE JAEKEL, WOLF-RUEDIGER KRAHNERT, ROCCO PACIELLO, and WOLFGANG SIEGEL Appeal 2014-006688 Application 12/307,4721 Technology Center 1600 Before DONALD E. ADAMS, JOHN G. NEW and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of preparing optically active 3-amino carboxylic ester compounds. The Examiner rejected the claims on appeal as obvious under 35 U.S.C. § 103(a). We AFFIRM. 1 According to Appellants, the real parties in interest is BASF SE, Germany. App. Br. 1. Appeal 2014-006688 Application 12/307,472 STATEMENT OF THE CASE Claims 1—19 are on appeal. Claim 1 is illustrative and reads as 1. A method for preparing optically active 3-amino carboxylic ester compounds of the general formula I, and the ammonium salts thereof, in which R1 is alkyl, cycloalkyl, heterocycloalkyl, aryl, or hetaryl, and R2 is alkyl, cycloalkyl or aryl, in which a mixture of enantiomers, emiched in one enantiomer, of a mono N-acylated 3-amino carboxylic ester of the general formula (l.b), in which R1 and R2 have the meanings indicated above, and R3 is hydrogen, alkyl, cycloalkyl or aryl, is subjected to a deacylation by addition of an acidic salt former, and to a subsequent further enantiomeric emichment by crystallization. follows: O 2 Appeal 2014-006688 Application 12/307,472 The Examiner rejected claim 1—19 under 35 U.S.C. § 103(a) over the combination of Onishi,2 Boaz,3 Zhang ‘495,4 Zhang ‘604,5 and Ovenden.6 ANALYSIS We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art and agree that the claims are obvious over Onishi, Boaz, Zhang ‘495, Zhang ‘604 and Ovenden. We address Appellants’ arguments below. Claims 1, 2, 4, 6—12, 15, and 16 Appellants argue claims 1, 2, 4, 6—12, 15 and 16 together as a group. We designate claim 1 as representative of the group. The Examiner found that Onishi disclosed the synthesis of P-amino acids as represented in the below reaction scheme. 0 Rxn 2 0 Rxn3 r 1 •""Rx NH X 8* ' v A/OT 2 Onishi et. al., JP 3493206 B2, published Feb. 3, 2004 (“Onishi”). 3 Boaz et al., The Preparation of Single Enantiomer 2-Naphthy alanine Derivatives Using Rhodium — Methyl BoPhoz-Catalyzed Asymmetric Hydrogenation, 9 Organic Process Research & Development 2005, 472-478 (2005) (“Boaz”). 4 Zhang et al, US 2005/0119495 Al, published June 2, 2005 (“Zhang 495”). 5 Zhang, US 2005/0159604 Al, published July 21, 2005 (“Zhang ‘604”). 6 Ovenden et al., Amphilactams A-D: NovelNematocides from Southern Australian Marine Sponges of the Genus Amphimedon, 64 (4) J. Org. Chem., 1140-1144 (1999) (“Ovenden”). 3 Appeal 2014-006688 Application 12/307,472 Non-Final Act. 3^4. In the above reaction scheme, as described by the Examiner, “Rxn 3 is a deacrylation reaction with an acid (e.g. hydrochloric acid) to give the free amine” enriched in the R enantiomer. Id. at 3. The Examine further found that Onishi taught “the generality of the reaction to not only carboxylic acids, but also to ester compounds.” Id. at 4. The Examiner acknowledged that Onishi did not teach enantiomeric enrichment by crystallization as recited in claim 1, but found that this element was supplied by Boaz. Id. at 4. The Examiner found that Boaz taught the synthesis of a-amino acids using enantioselective hydrogenation to give “an enriched enantiomeric mixture of the ester,” followed by “an N- deacylation reaction ... to give the free amine as the R enantiomer.” Id. The Examiner found that Boaz further taught that “enhancement of the ee [enantiomeric excess] can be achieved by crystallization with methanesulfonic acid to form the salt.” Id. The Examiner further found that crystallization was a common laboratory procedure, and an obvious purification method. Id. at 5. Appellants argue that the reaction described in Onishi discloses the stereoselective hydrogenation of an N-acylated, a-unsaturated (Z)-3 amino carboxylic acid and that this method cannot be applied to esters. App. Br. 8— 9. We are not persuaded. In finding that the method of Onishi could be extended to esters, the Examiner relied on Onishi’s discussion of the “Prior art and Problems to be Resolved by the Invention.”7 Ans 2—3; Onishi 13^4. Among the problems 7 The Examiner also found that “the acid and ester functionality are not involved in the chemical transformation in question and are merely bystander functional groups.” Ans. 3. 4 Appeal 2014-006688 Application 12/307,472 discussed in Onishi are asymmetric hydrogenation reactions for obtaining esters including 3-acetamidobutanoic acid methyl ester, 3-acetamido-5- methylhexanoic acid methyl ester and 3-acetoxy-3-phenylhexanoic acid methyl ester. Onishi 14. Onishi describes the problems as follows: [W]ith asymmetric hydrogenation reactions in which ruthenium complexes are used as [a] catalyst it has been reported [Tetrahedron Asymmetry, 1991, 2, 543-554] that 3-acetamidobutanoic acid methyl ester was obtained with an optical purity of 96% ee with (E)-3-acetamido-2- butenoic acid methyl ester as substrate and that 3- acetamido-5-methylhexanoic acid methyl ester and 3- acetoxy-3-phenylhexanoic acid methyl ester with optical purities of 90% ee were obtained from (E)-3-actamido-5- methyl-2-hexenoic methyl ester and (E)-3-acetamido-3- phenyl-2-propenoic acid methyl ester respectively, but in this report it is also indicated that while in those cases where the olefin-acid ester[,] which was the substrate[,] had the (E) form configuration[,] the hydrogenated product had a high optical purity, in those cases where geometrical isomers which had the (Z) form configuration were used as substrates the hydrogenated products had a low optical purity with a maximum of 9% ee. Id. After discussing the “Prior Art and Problems to be Resolved by the Invention,” including problems with relating to ester compounds, Onishi provides a discussion entitled “Means of Resolving These Problems.” Id. at 1 5. Onishi proceeds to discuss the stereoselective reaction relied upon by the Examiner. Based on the plain language of Onishi, the reaction relied upon by the Examiner, which is exemplified by an N-acylated, a-unsaturated (Z)-3 amino carboxylic acid, solved the problems described in the “Prior Art and Problems to be Resolved by the Invention” section. As these problems included stereoselection in ester compounds, the record supports the 5 Appeal 2014-006688 Application 12/307,472 Examiner’s finding that Onishi’s solution — exemplified using carboxylic acid — extended to ester compounds. Appellants disagree with the Examiner’s interpretation of paragraph 4 of Onishi, but the Examiner’s interpretation is supported by the plain language of the reference. Appellants argue that Onishi’s teaching that ester isomers in the Z configuration had low optical purity would have discouraged the person of ordinary skill from applying Onishi’s methods to esters (App. Br. 9), and reflects the unpredictability of working with esters. Reply Br. 5—6. As discussed above, however, Onishi teaches that its method resolves these problems. After reviewing the record, we find that Appellants have not established a persuasive evidentiary basis to support their contention that the Examiner is wrong that Onishi’s teachings apply to esters. See Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989); (“Attorneys’ argument is no substitute for evidence.”); In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Appellants argue that the Examiner erred in combining the teachings of Boaz with those of Onishi because Boaz relates to a-amino acids while Onishi relates to P-amino acids. App. Br. 10. Appellants argue that the Examiner failed to articulate a reason why a person of ordinary skill in the art would substitute a-amino acids and P-amino acids. Id. We are not persuaded that Appellants have identified reversible error. The Examiner relied upon Boaz for its teaching that optical purity could be was enhanced by crystallization. Ans. 6. The Examiner found that crystallization was a common laboratory purification procedure. Non-Final Act. 5. Appellants have not established a persuasive evidentiary basis on 6 Appeal 2014-006688 Application 12/307,472 which to find that a teaching that crystallization enhances the purity of a- amino acids would not apply to P-amino acids. Appellants allege that the claimed method provides unexpected results in that it produces “optically active 3-amino carboxylic esters with an enantiomeric excess (ee) of approximately at least 98%.” App. Br. 10. Appellants contend “[tjhere is no disclosure in the prior art of a process of forming comparably optically active 3-amino carboxylic esters.” Id. at 11. We are not persuaded because Appellants do not compare the ee optical purity of 3-amino carboxylic esters produced using its method to the purity of 3-amino carboxylic esters obtained by any other method. Accordingly, we affirm the Examiner’s rejection of claim 1 over the combination of Onishi, Boaz and Ovenden. Because they were not argued separately, claims 2, 4, 6—12, 15 and 16 fall with claim 1. Claim 3 Claim 3 depends from claim 2 and additionally requires that “a 8-keto ester of the formula 1.1 is reacted with at least one carboxamide of the formula R3-C(0)NH2 in the presence of an amidation catalyst with removal of the water of reaction to give a 3-amino carboxylic ester of the formula I.a.” In their opening brief, Appellants argued that the Examiner “failed to establish where in any of the cited references this reaction is disclosed.” App. Br. 11. The Examiner’s Answer specifically identified this reaction as being disclosed in Ovenden. Ans. 11—12. Appellants do provide any reason why the Examiner’s identification of this reaction as being disclosed in Ovenden is in error, instead arguing that claim 3 is patentable for the reasons 1, 2, 4, 6—12, 15 and 16 are patentable. Reply Br. 15—16. Accordingly, we 7 Appeal 2014-006688 Application 12/307,472 affirm the Examiner’s rejection of claim 3 for the reasons already provided in connection with claims 1, 2, 4, 6—12, 15 and 16. Claim 5 Claim 5 depends from claim 1 and additionally requires that “the enantiomer-enriching crystallization is carried out with addition of an ester.” The Examiner found that crystallization using different solvents was a common laboratory procedure (Non-Final Act. 5), and provided several examples where ethyl acetate — an ester — was used in purification and recrystallization procedures. Ans. 13 (citing examples from Zhang ‘495, Ovenden and Boaz). Appellants argue that the examples provided by the Examiner do not involve the claimed 3-amino carboxylic compounds and additionally, with respect to two of the four examples cited by the examiner, do not involve recrystallization. Reply Br. 17—21. We are not persuaded. The examples provided by the Examiner establish that ethyl acetate, an ester, is a solvent that is useful for purification and recrystallization. Having established, based on Boaz, that recrystallization enhances enantiomeric purity, it would have been obvious to carry out recrystallization with a solvent, like ethyl acetate, that is known to be useful for purification and recrystallization. Accordingly, we affirm the Examiner’s rejection of claim 5. Claims 13 and 14 Claims 13 and 14 depend from claim 2 and additionally require that at least one step of claim 2 is carried out “continuously.” Claim 14 further specifies that the continuous reaction is hydrogenation. 8 Appeal 2014-006688 Application 12/307,472 The Examiner contends that continuous reactions are common process modifications. Non-Final Act. 6. The Examiner notes that Boaz “teaches the scale-up potential of the synthesis.” Id. The Examiner further notes that Onishi discloses performing the hydrogenation reaction for 24 hours and Boaz teaches performing hydrogenation for 6 hours. Ans. 14. Appellants argue that the claims do not require scale up and that the disclosures “highlight that the processes of Onishi and Boaz are carried out in a single distinct stage rather than being performed continuously.” Reply Br. 22. We find that the Examiner has the better position. In arguing that a 24 hour hydrogenation reaction (as disclosed in Onishi) is not “continuous” because it is “carried out in a single distinct stage,” Appellants implicitly contend that the term “continuous” should be construed to require that the reaction continue indefinitely with no temporal end point (or at least for a period longer than 24 hours). Reply Br. 22. We do not agree with this construction. Instead, we find that the term “continuous” is more reasonably construed to mean “without interruption.” This is consistent with how the term is used in the Specification. See, Specification 15. Appellants do not identify any disclosure in Onishi or Boaz teaching interruption of the hydrogenation reaction. Accordingly, we affirm the Examiner’s rejection of claims 13 and 14. Claims 17 and 19 Claims 17 and 19 depend from claim 1. Claim 17 adds a limitation requiring that “the value of ee for the solid isolated after the crystallization is at least 98%.” Claim 19 adds a limitation requiring that the optically active 9 Appeal 2014-006688 Application 12/307,472 3-amino carboxylic ester compounds produced have an enantiomeric excess of at least 98%.” Appellants argue that it the claimed purity would not have been obvious because it was not predictable. Reply Br. 23—25. We disagree. A newly-discovered result or property of an existing (or obvious) method of use is not patentable. See Abbott Labs. v. Baxter Pharm. Prods., 471 F.3d 1363, 1368-69 (Fed. Cir. 2006); Brassica Prot. Prods. LLCv. Sunrise Farms (In re Cruciferous Sprout Litig.), 301 F.3d 1343, 1350-51 & n.4 (Fed. Cir. 2002); and Bristol-Myers Squibb Co. v. Ben Venue Labs., 246 F.3d 1368, 1376 (Fed. Cir. 2001). Accordingly, we affirm the Examiner’s rejection of claims 17 and 19. Claim 18 depends from claim 1 and additionally requires that “an optically active compound of the formula II or the ammonium salts thereof with the following absolute configuration, or the optically active enantiomer of this compound or salts, is obtained, where R2 is C1-C6 alkyl.” The Examiner’s reasoning and Appellants’ arguments with respect to claim 18 are substantially the same as their reasoning and arguments with respect to claim 1. Accordingly we affirm the Examiner’s rejection of claim Claim 18 HM H O d (II) OR2 10 Appeal 2014-006688 Application 12/307,472 18 for the reasons discussed provided above with respect to claims 1, 2, 4, 6—12, 15 and 16. SUMMARY For these reasons and those set forth in the Examiner’s Answer, and the Non-Final Office Action, the Examiner’s Final decision to reject claims 1—19 is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1). AFFIRMED 11 Copy with citationCopy as parenthetical citation