10977753 (B.P.A.I. Mar. 26, 2012)

Ex Parte Banholzer et al

Board of Patent Appeals and InterferencesMar 26, 2012

10977753 (B.P.A.I. Mar. 26, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte ROLF BANHOLZER, WALDEMAR PFRENGLE, and PETER SIEGER __________ Appeal 2011-008405 Application 10/977,753 Technology Center 1600 __________ Before LORA M. GREEN, JEFFREY N. FREDMAN, and STEPHEN WALSH, Administrative Patent Judges. Opinion filed for the Board by WALSH, Administrative Patent Judge. Opinion concurring filed by FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) from the rejection of claims directed to a process for preparing tiotropium salts. The Patent Examiner rejected the claims for obviousness and, provisionally, for obviousness-type double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. Appeal 2011-008405 Application 10/977,753 2 STATEMENT OF THE CASE Claims 1-6 and 8-11 are on appeal. Claim 1 is representative and reads as follows: 1. A process for preparing tiotropium salts of formula 1 wherein X- denotes an anion other than Y-, optionally in the form of solvates or hydrates thereof, selected from the group consisting of fluoride, chloride, bromide, iodide, C1-C4-alkylsulphate, sulphate, hydrogen sulphate, phosphate, hydrogen phosphate, dihydrogen phosphate, nitrate, maleate, acetate, trifluoroacetate, citrate, fumarate, tartrate, oxalate, succinate and benzoate, C1-C4-alkylsulphonate, which may optionally be mono-, di- or trisubstituted by fluorine at the alkyl group, or phenylsulphonate, which may optionally be mono- or polysubstituted by C1-C4-alkyl at the phenyl ring, comprising reacting a tiotropium salt of formula 2 wherein Y- denotes an anion other than X-, selected from the group consisting of halide, C1-C10-alkylsulphonate, C1-C10-alkylsulphate, C6-C10- arylsulphonate, optionally in the form of solvates or hydrates thereof, in a suitable solvent with an ion source Kat-X wherein Kat denotes a cation and X has the same definition as X- above. The Examiner rejected the claims as follows: Appeal 2011-008405 Application 10/977,753 3  claims 1-6 and 8-111 under 35 U.S.C. § 103(a) as unpatentable over Banholzer et al. (US 6,486,321 B2, issued Nov. 26, 2002) and Mizzoni (US 3,551,492, issued Dec. 29, 1970); and  claims 1-6 and 8-11 under 35 U.S.C. § 103(a) as unpatentable over claims 1-16 of copending Application No. 11/424,244 in view of Mizzoni and Banholzer. OBVIOUSNESS The Examiner finds that “[t]he compounds are known , ( as per Banho[l]zer reference[]) which also teaches a process of making a Bromide salt.” (Ans. 5-7, citing Banholzer, cols. 4 and 11.) The Examiner finds “[t]hus the primary reference teaches the compounds and a generic method of converting it form [sic] one salt to another.” (Id. at 8.) The Examiner finds that Mizzoni taught “making salts via an exchange salts.” (Id., citing Mizzoni col. 4.) The Examiner finds that “the process of exchanging the ions in a tertiary amine is well known to a person skilled in the art. Applicants[’] compounds are also tertiary ammonium salts.” (Id. at 10.) The Examiner concludes: “Thus one skilled in the art of making pharmaceutical salts, especially if it is a tertiary amine would be motivated to use the Mozzini reference reagent to change one anion to another.” (Id.) We reverse this rejection for failure to present a prima facie case of obviousness. “[R]ejections 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 1 Although the Answer states that claims 1-11 are rejected, Appellants state that claim 7 has been cancelled. (App. Br. 2.) Appeal 2011-008405 Application 10/977,753 4 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). A critical deficiency, among others, in the rejection is that it provides no evidence that a person of ordinary skill in the art would have had a reason to convert Banholzer’s tiotropium bromide to a different salt. OBVIOUSNESS-TYPE DOUBLE PATENTING The Examiner finds “[t]he copending application is drawn to a process of converting the bicarbonate salt to another salts which can be a halide sulphate phosphate and so on.” (Ans. 12.) The Examiner finds that “[t]he Mizzoni reference teaches a process of converting a quaternary ammonium salt ( can be a carbonate) to a halide or another salt by using a an acid see lines 15 to 70 of column 4.” (Id.) The Examiner finds that “[o]rganic synthesis is full of many generic steps that involve standard reactions for specific functional group. . . . thus a person motivated to perform a certain reaction would be motivated to use a standard reaction to convert one ammonium salt to another, with a reasonable expectation of success.” (Id. at 13.) We reverse this rejection. A critical deficiency in the rejection, among others, is that it provides no evidence that a person of ordinary skill in the art would have had a reason to convert the copending claim process to Appellants’ claimed process. SUMMARY We reverse the rejection of claims 1-6 and 8-11 under 35 U.S.C. § 103(a) as unpatentable over Banholzer and Mizzoni. Appeal 2011-008405 Application 10/977,753 5 We reverse the rejection of claims 1-6 and 8-11 under 35 U.S.C. § 103(a) as unpatentable over claims 1-16 of copending Application No. 11/424,244 in view of Mizzoni and Banholzer. REVERSED cdc Appeal 2011-008405 Application 10/977,753 6 CONCURRING OPINION Fredman, Administrative Patent Judge While I concur with the Majority’s analysis, I would have composed a New Grounds of Rejection under 35 U.S.C. § 103(a) citing Bechtold-Peters,2 (available under § 102(b)) in combination with the Examiner’s current references. The fundamental flaw in the Examiner’s current obviousness case was the absence of any reason to convert the tiotropium bromide to another salt. Bechtold-Peters teaches that by “tiotropium is meant the free ammonium cation. The counter-ion (anion) may be chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate or methyl sulphate. Of these anions, the bromide is preferred” (Bechtold-Peters 1-2 ¶ 0012). Bechtold-Peters further teaches that: According to the invention, any reference to tiotropium, which is the free ammonium cation, corresponds to a reference to tiotropium in the form of a salt (tiotropium salt) which contains an anion as the counter-ion. Tiotropium salts which may be used within the scope of the present invention are those compounds which contain chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate or methyl sulphate, in addition to tiotropium as counterion (anion). Within the scope of the present invention, tiotropium bromide is preferred of all the tiotropium salts. (Bechtold-Peters 3 ¶ 0033.) 2 Bechtold-Peters et al., US 2002/0110529 A1, published Aug. 15, 2002, cited in the IDS filed Sep. 30, 2010. Appeal 2011-008405 Application 10/977,753 7 Thus, Bechtold-Peters demonstrates that the chloride salt, among others, was a known equivalent salt which would have reasonably been expected to function as an equivalent to the preferred bromide salt. An “[e]xpress suggestion to substitute one equivalent for another need not be present to render such substitution obvious.” In re Fout, 675 F.2d 297, 301 (CCPA 1982). As noted by the Court in KSR, “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). The facts in this situation are similar to those in Pfizer, where the Federal Circuit considered the obviousness of the besylate salt where the art taught that 53 salts were feasible alternatives and the besylate showed better tableting than maleate. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007). The court found that at “most, then, Pfizer engaged in routine, verification testing to optimize selection of one of several known and clearly suggested pharmaceutically-acceptable salts to ease its commercial manufacturing and marketing of the tablet form of the therapeutic.” Id. The court continues that the “fact that amlodipine besylate was the best of the seven acid addition salts actually tested proves nothing more than routine optimization that would have been obvious to one of ordinary skill in the art.” Id. Relying on the Examiner’s prior art and the teaching of Bechtold- Peters that the chloride and bromide salts are known equivalents, I would further rely on Fout, KSR, and Pfizer, to support the conclusion that replacing the bromide with the chloride or other disclosed salts in Bechtold- Peters represents routine substitution of an obvious equivalent. I would then conclude that this substitution provides a reason to alter the anion of the tiotropium salt as required by claim 1.