Ex Parte Ludescher et alDownload PDFPatent Trial and Appeal BoardDec 8, 201612093657 (P.T.A.B. Dec. 8, 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. 12/093,657 05/14/2008 Johannes Ludescher 16511-34627 4928 90042 7590 12/12/2016 MANET T T NFT TFR PT T C EXAMINER 1725 I Street, N.W. STEELE, AMBER D Suite 300 Washington DC, DC 20006 ART UNIT PAPER NUMBER 1676 NOTIFICATION DATE DELIVERY MODE 12/12/2016 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): melcher @ mdslaw .com j effsmelcher @ att. net PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JOHANNES LUDESCHER, INGOLF MACHER, OLE STORM, and STEPHAN BERTEL1 Appeal 2015-005582 Application 12/093,657 Technology Center 1600 Before DEMETRA J. MILLS, ULRIKE W. JENKS 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 process for producing an aza cyclohexapeptide compound. The Examiner rejected the claims on appeal for failure to comply with the written description requirement under 35 U.S.C. § 112(a) and as obvious under 35 U.S.C. § 103(a). We reverse. STATEMENT OF THE CASE Claims 15 and 17 are on appeal. Claim 15, the only independent claim, is illustrative and reads as follows: 1 Appellants identify the Real Party in Interest as Sandoz AG. Br. 1. Appeal 2015-005582 Application 12/093,657 15. A process for producing an aza cyclohexapeptide compound of formula 1 the steps of: a) reducing a compound of formula II or an acid addition salt thereof OH to obtain a compound of formula I or a pharmaceutically acceptable salt thereof, and b) optionally isolating the compound of formula I or the pharmaceutically acceptable salt thereof, wherein X is NR1R2 and wherein 2 Appeal 2015-005582 Application 12/093,657 Ri is H, Ci-Cg alkyl, C3-C4 alkenyl, (CH2)2-40H or (CH2)2-4NR3R4; R2 is H, Ci-C8 alkyl, C3-C4 alkenyl, (CH2)2-40H, (CH2)2- 4NR3R4 or wherein NR1R2 form a heterocyclic ring and Ri and R2 together are (CH2)4, (CH2)5, (CH2)20(CH2)2, or (CH2)2NH(CH2)2; R3 is H, Ci-Cg alkyl; and R4 is H, Ci-Cg alkyl. In response to a restriction requirement, Appellants elected the following species: the starting material of Formula II wherein X = HN-CH2- CH2-NH2, a single step conversion of Formula II to Formula I, and a final product of Formula I wherein X = HN-CH2-CH2-NH2. Final Act. 2—3. The claims stand rejected as follows: Claims 15 and 17 under 35 U.S.C. § 112(a) as unpatentable for failure to comply with the written description requirement. Claims 15 and 17 under 35 U.S.C. § 103(a) as unpatentable over the combination of Balkovec ’8042 and Balkovec ’245.3 Claim 15 and 17 under 35 U.S.C. § 103(a) as unpatentable over the combination of Balkovec ’6054 and Balkovec ’245. 2 Balkovec et al., US Patent No. 5,378,804, issued Jan. 3, 1995 (“Balkovec ’804”). 3 Balkovec et al., US Patent No. 5,646,245, issued July 8, 1997 (“Balkovec ’245”). 4 Balkovec et al., US Patent No. 5,514,650, issued May 7, 1996 (“Balkovec ’650”). 3 Appeal 2015-005582 Application 12/093,657 ANALYSIS Appellants argue claims 15 and 17 together as a group. We designate claim 15 as representative. We limit discussion and consideration to the elected species, and take no position respecting the patentability of the broader generic claims, including the remaining, non-elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. Int. 1987). Written Description Claim 15 is drawn to a method for producing aza cyclohexapeptide comprising reducing a nitrile (the compound of Formula II) to an amine (the compound of Formula I). The claim is not limited in the manner the reduction is accomplished, and encompasses any reducing agent capable of converting the claimed nitrile to the claimed amine. With respect to reducing agents, the Specification states: The reduction of compounds of formula II or acid addition salts thereof in step a) to obtain compounds of formula I may be performed by using any nitrile reducing agent. Preferably, catalytic hydrogenation is applied. Catalysts suitable for the reduction are e.g. catalysts originating from noble metals e.g. palladium, platinum, rhodium, ruthenium, e.g. HRh(PR3)3 wherein R represents an optionally substituted phenylgroup or an alkylgroup, e.g. isopropyl, Rh/Al203, CIR(PR3)3, Pt, Pt02, Pd, Pd on carbon or Ru or RuC12 or catalyst such as nickel. Preferably, Rh/Al203 or Pd on carbon is used as catalyst. The hydrogen source may be H2 or generated in situ e.g. from ammonium formiate or diimine reactions. Preferably, H2 is used. Specification p. 14,11. 14—21. 4 Appeal 2015-005582 Application 12/093,657 The Examiner found that the Specification’s disclosure of catalysts originating from palladium, platinum, rhodium, ruthenium did not convey to those of skill in the art that the inventors were in possession of the full scope of the reducing agents encompassed by the claim. Final Act. 3—5. The Examiner noted that “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.” Ans. 9. Here, the Examiner found that the Specification provided examples only of nobel metal catalysts and that even within the subgenus of noble metal catalysts, there was variability in yield resulting from the claimed reduction. Id. at 8. Appellants contend that the invention is sufficiently described based on the examples provided in the specification and the general knowledge of one skilled in the art. App. Br. 6. Appellants assert that the novelty of the claimed invention lies not in the reducing agent, but in “the use of the intermediate of Formula II to directly form the compound of Formula I.” Reply Br. 1—2. Appellants argue: The reducing agent and/or the reduction reaction conditions are not essential; they just have to be suitable for reducing Formula II to form the compound of Formula I. As put forth on page 5 of the Appellant’s Brief, the originally filed written specification discloses preferred examples of nitrile reducing agents on page 14, lines 15—21, as well as preferred reduction reaction conditions, e.g. on page 14, lines 23 to page 15, lines 1 and 2. As admitted by the Examiner, the present application discloses nine working examples, whereof Examples 3 to 5 utilize different reducing conditions and reducing agents. See paragraph bridging page 7 and 8, of the Answer. Based on this disclosure and the common general knowledge, the skilled person can easily choose 5 Appeal 2015-005582 Application 12/093,657 an appropriate reducing agent and perform the invention without undue experimentation. Reply Br. 2. We find that Appellants have the better position. “[T]he test for sufficiency of support in a parent application is whether the disclosure of the application rel ied upon ‘reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter.’” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir, 1991). Addressing the written description requirement in the context of a genus of compounds, the CCPA stated: The written description of a class of compounds must provide a measure of predictability lor the utility described for that class. That is to say: would the worker of ordinary skill in this art consider [the claimed genus of compounds] to be operative when considering the [application’s] disclosure? It is incumbent, in the first instance, for the PTO to give reasons why he would not. In re Herschler, 591 F.2d 693, 701 (CCPA 1979). Here, the Specification teaches that the claimed reduction can be performed using “any nitrile reducing agent.” Specification p. 14,1. 15. The Specification also identifies a number of specific reducing agents, id. at p. 14,11. 16—21, and provides working examples utilizing certain of these reducing agents. Id. at p. 28—29 (examples 3—5). The Examiner contends that the genus of reducing agents is unpredictable because there is variation in the yields produced using the reducing agents disclosed in the specification. Ans. 8—10. The claims, however, do not require any particular yield. And the Examiner has not provided any reason why the person of skill in the art would not have considered the genus of reducing 6 Appeal 2015-005582 Application 12/093,657 agents to be operative in view of the Specification’s disclosure that “any nitrile reducing agent” can be used. Indeed, in connection with the obviousness rejection, the Examiner noted that reducing a nitrile into an amine was a “known technique” that was “recognized as part of the ordinary capabilities of one skilled in the art.” Id. at 5. Accordingly we find that the Specification’s general teaching that “any nitrile reducing agent” can be used, together with the specific examples provided and the general knowledge in the art sufficiently conveyed to the person of ordinary skill in the art that the inventors were in possession of the claimed invention. Obviousness over Balkovec ’804 and Balkovec ’245 The Examiner found that Balkovec ’804 taught “methods of producing aza cyclohexapeptide compounds (i.e. caspofimgin).. .” Ans. 4. The Examiner further found that Balkovec ’804 taught “reducing nitrile via nickel (II) chloride and sodium borohydride, sodium borohydride with cobaltous chloride, and generally discuss[es] nitrile reduction via chemical or catalytic reduction.” Id. at 4—5. The Examiner acknowledged, however that the examples of preparing echinocandin compounds by “reducing the nitrile into an amine” involve “a different species of echinocandin compound” than is recited in the claims. Id. at 11. The Examiner found that Balkovec ’245 also taught “cyclohexapeptide compounds and nitrile reduction.” Id. at 5. In Balkovec ’245, the reduction is accomplished “via sodium borohydride with cobaltous chloride or catalytic hydrogenation utilizing palladium on carbon, platinum oxide, or rhodium on alumina.” Id. 7 Appeal 2015-005582 Application 12/093,657 The Examiner concluded that the teachings of Balkovec ’804 and Balkovec ’245 render the claimed process obvious “because a particular known technique (i.e. reducing a nitrile into an amine for production of echinocandin compounds wherein caspofimgin is a member of the echinocandin class of antifimgals) was recognized as part of the ordinary capabilities of one skilled in the art.” Id. Appellants contend, inter alia, that the person of ordinary skill would not have been motivated to prepare caspofimgin by reducing the compound of Formula II because Balkovec ’804 teaches that compounds like caspofimgin “must” be formed by the process described in Examples 1—3 of Balkovec ’804. App. Br. 8. Appellants also argue that the low yields disclosed in Balkovec ‘804 (44% in Example 10B, 72% in Example 9) when nitrile was reduced to amine in compounds other than caspofimgin would have discouraged the person of ordinary skill from applying these reduction methods to caspofimgin intermediates. Id. at 12—13. We find that Appellants have the better position. As an initial matter, there appears to be some dispute as to whether Balkovec ’804 discloses a compound of Formula II. The Examiner states that “Balkovec et al. (‘804) teach[es] methods of producing aza cyclohexapeptide compounds (i.e. caspofimgin) comprising utilizing reagents including present formulas I and II wherein X can be HNCH2CH2NH2.” Ans. 4 (citing “the entire specification particularly the abstract; columns 1—4; Examples 2, 8, and 10”). Appellants assert that “[njeither of Balkovec ’804 or ’245 disclose or suggest the formula II.” 8 Appeal 2015-005582 Application 12/093,657 Reply Br. 9. We have reviewed Balkovec ’804 and cannot discern a compound meeting the structure of Formula II. Even assuming that Balkovec ’804 does disclose the compound of Formula II, the Examiner must articulate some reason to select the compound of Formula II and reduce it to obtain the compound of Formula I. We find that the Examiner has not meet this burden. See In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006) (explaining that “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.”). While the record supports the Examiner’s assertion that the reduction of a nitrile to amino was a “known technique,” see Ans. 5, this does not, by itself, render the claimed process obvious. This is particularly true given Balkovec ’804’s teaching that the method of Examples 1—3, which does not include reduction of a nitrile group, “must be employed to obtain a useful yield of product [like Formula I of claim 1] when Ri is OH.” Balkovec ’804 col. 14,11. 49—54. The Examiner does not explain why, in the face of this teaching, the person of ordinary skill in the art would have used a method other than the method of Examples 1—3 of Balkovec to obtain Formula 1. The Examiner has not presented a sufficiently articulated rationale why the person of ordinary skill in the art would have selected the compound of Formula II, if present, as a starting point for producing the compound of Formula I. Accordingly, we reverse the Examiner’s decision to reject claims 15 and 17 as obvious over Balkovec and Balkovec ’245. 9 Appeal 2015-005582 Application 12/093,657 Obviousness over Balkovec ’605 and Balkovec ’245 Balkovec ’650 is a continuation of Balkovec ’804 and thus contains an identical disclosure to that of Balkovec ’804. Accordingly we reverse the Examiner’s rejection of claims 15 and 17 over the combination of Balkovec ’605 and Balkovec ’245 for the same reasons we reversed the Examiner’s rejection of claims 15 and 17 over the combination of Balkovec ’804 and Balkovec ’245. SUMMARY For the reasons set forth herein, the Examiner’s final decision to reject claims 15 and 17 is reversed. REVERSED 10 Copy with citationCopy as parenthetical citation