Ex Parte Banholzer et alDownload PDFPatent Trial and Appeal BoardSep 26, 201310976688 (P.T.A.B. Sep. 26, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ROLF BANHOLZER, WALDEMAR PFRENGLE, and PETER SIEGER __________ Appeal 2013-006374 Application 10/976,688 Technology Center 1600 __________ Before DEMETRA J. MILLS, LORA M. GREEN, and JEFFREY N. FREDMAN, Administrative Patent Judges. GREEN, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal1 under 35 U.S.C. § 134 from the Examiner’s rejection of claims 1-5.2 We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 The Real Party in Interest is Boehringer Ingelheim International GmbH (App. Br. 1). 2 Claims 6-30 are also pending, but stand withdrawn from consideration (App. Br. 2). App App wher there wher optio defin Banh 3 Mi 4 Ban 5 Bec eal 2013-0 lication 10 Claim 1, 1. A pro ein X‾ den of, comprisi ein Y‾ den nally in th in a suita ition as X The clai • Claim olzer4 and zzoni, 3,55 holzer et htold-Pet 06374 /976,688 ST the only i cess for p otes an an ng reactin otes an an e form of ble solven ‾ above. ms stand r s 1-5 unde Bechtold 1,492, iss al., 6,486,3 ers et al., 2 ATEMEN ndependen reparing ti ion, optio g a tiotrop ion other solvates o t with a sa ejected as r 35 U.S.C -Peters5 (A ued Dec. 2 21 B2, iss 002/01105 2 T OF TH t claim on otropium s nally in th ium salt o than X‾ an r hydrates lt Ag-X, w follows: . § 103(a) ns. 4-13); 9, 1970. ued Nov. 29 A1, pu E CASE appeal, re alts of for e form of s f formula 2 d is select thereof, herein X in view o 26, 2002. blished A ads as fol mula 1 olvates or ed from ha has the sa f Mizzoni, ug. 15, 20 lows: hydrates lides, me 3 02. Appeal 2013-006374 Application 10/976,688 3 • Claims 1-5 on the ground of nonstatutory obviousness-type double patenting over claims 1-16 of copending Application No. 11/424,2446 in view of Mizzoni, Banholzer, DeSilva7 and Bechtold-Peters (Ans. 13-15). I. Issue The Examiner has rejected claims 1-5 under 35 U.S.C. § 103(a) as obvious in view of Mizzoni, Banholzer and Bechtold-Peters. The Examiner finds that Banholzer teaches a tiotropium bromide compound, the use of the compound, as well as a process of making it (Ans. 6). The Examiner finds further that Mizzoni discloses a process of converting one quaternary ammonium salt to another with the use of Ag-X, wherein “X” may be a chloride ion when the quaternary ammonium chloride is desired (id. at 8). The Examiner also finds that Bechtold-Peters teaches tiotropium salts in which the counter-ion (anion) may be chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate or methylsulphate (id. at 10). The Examiner concludes that Bechtold-Peters provides a reason as to “why one would want to convert one salt form to another” (id. at 13). That is, as Mizzoni “teaches the use of an alkylhalide to covert the compound into a different quaternary ammonium salt,” it would have well within the level of skill of the ordinary artisan to use the process of Mizzoni to convert between the different salts as taught by Banholzer and Bechtold-Peters (id.). 6 Application No. 11/424,244, filed Jun. 15, 2006. 7 DeSilva, ESSENTIALS OF ION EXCHANGE (Presented at the 25th Annual WQA Conference, March 17, 1999). Appeal 2013-006374 Application 10/976,688 4 Appellants contend that the cited references would not have made obvious the claim 1 process for preparing tiotropium salts because one of skill in the art would not have been motivated to apply Mizzoni’s process for converting a quaternary ammonium salt having first anion to a quaternary ammonium salt having a second anion to tiotropium (Appeal Br. 7-10). The issue presented is: Does the evidence of record support the Examiner’s conclusion that one of skill in the art would have been motivated to apply Mizzoni’s process for converting a quaternary ammonium salt from a first anion to a second anion to the tiotropium salts of Banholzer and Bechtold-Peters to obtain tiotropium salts having alternative anions? Findings of Fact FF1. Banholzer discloses tiotropium bromide with the following formula: (Banholzer, col. 1, ll. 19-44), as well as a process for preparing it (id. at col. 1, ll. 12-15). FF2. Banholzer discloses that tiotropium bromide is an “anticholinergic and can therefore provide therapeutic benefit in the treatment of asthma or COPD (chronic obstructive pulmonary disease)” (id. at col. 1, ll. 45-47). Appeal 2013-006374 Application 10/976,688 5 FF3. Bechtold-Peters discloses “powdered preparations containing tiotropium for inhalation” (Bechtold-Peters 1, ¶ 0002). FF4. Bechtold-Peters discloses that “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” (id. at 3, ¶ 0033). According to Bechtold-Peter, the “counter-ion (anion) may be chloride, bromide, iodide, methanesulphonate, para- toluenesulphonate or methyl sulphate. Of these anions, the bromide is preferred” (id. at 1-2, ¶ 0012). FF5. Mizzoni discloses new N,N’-aralkyl-alkylenediamines … of Formula I in which each of Am1 and Am2 is secondary or tertiary amino, each of alk1, alk2, alk4 and alk5 is lower alkylene separating two hetero-atoms by at least two carbon atoms, alk3 is alkylene separating the nitrogen atoms by at least 6 carbon atoms, each of Ph1 and Ph2 is a phenylene radical and each of R1 and R2 is hydrogen or lower alkyl, N-oxides, quaternaries and salts thereof … . (Mizzoni, col. 1, ll. 33-45.) FF6. Mizzoni discloses that a “quaternary ammonium salt is … converted directly into another quaternary ammonium salt; for example, a quaternary ammonium iodide, when reacted with freshly prepared silver chloride or with hydrochloric acid in anhydrous methanol, yields the desired quaternary ammonium chloride” (id. at col. 4, ll. 29-34). Appeal 2013-006374 Application 10/976,688 6 Principles of Law “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc, 550 U.S. 398, 416 (2007). If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill. Id. at 417. In determining whether obviousness is established by combining the teachings of the prior art, “the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art.” In re Keller, 642 F.2d 413, 425 (CCPA 1981). Analysis Claim 1 is directed to a process for preparing tiotropium salts having an anion X that is selected from halides by reacting a triotropium salt having an anion Y with a salt Ag-X in a suitable solvent, such that anion Y is different from anion X. Banholzer discloses that tiotropium bromide, a quaternary ammonium salt, is effective for the treatment of asthma or chronic obstructive pulmonary disease. Bechtold-Peters discloses inhalation powder preparations containing tiotropium, such that the tiotropium is in salt form and has an anion that may be chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate or methyl sulphate. Mizzoni discloses that a quaternary ammonium salt, e.g. a quaternary ammonium iodide, can be Appeal 2013-006374 Application 10/976,688 7 converted directly into another quaternary ammonium salt when reacted with, for example, silver chloride, to yield a quaternary ammonium chloride. Thus, it would have been obvious for one of skill in the art to use Mizzoni’s method of ammonium salt conversion to convert one tiotropium salt, e.g. tiotropium iodide, to another tiotropium salt such as tiotropium chloride because Bechtold-Peters teaches that a variety of tiotropium salts may be used in the inhalation powders. Appellants argue that “even if Bechtold-Peters did provide one of ordinary skill in the art a reason to provide a different salt of tiotropium, the rejection still lacks sufficient support” (Appeal Br. 5). Appellants argue that “[t]here is still no teaching in any of the Banholzer, Mizzoni or Bechtold- Peters references of a method for actually converting one tiotropium salt to another by the particular method claimed” (id.). Appellants argue that “Bechthold-Peters [sic] … merely indicates the existence of optional tiotropium salts,” but not methods to convert one to the other (id.). That argument is not persuasive. The cited references provide evidence that the all of the elements of claim 1 are known, i.e. the usefulness of different salts for tiotropium and a method of converting one ammonium salt to another using a silver salt to provide an alternative anion. Thus, application of the known conversion method to tiotropium salts appears to be a predictable variation of an art-recognized method to yield predictable results. In accord with In re Keller, the test for obviousness is what the combined teachings of the references would have suggested to those of ordinary skill in the art. Appeal 2013-006374 Application 10/976,688 8 Appellants argue that “Mizzoni’s teachings are limited to N,N’- aralkyl-alkylenediamines” (Reply Br. 1; see also App. Br. 5). Appellants argue that “[t]here is no reason explained or apparent on the record why one of ordinary skill in the art would consider such teachings to be applicable to structurally very distinct tiotropium salts” (Reply Br. 1-2). Appellants argue that “the starting material is obviously not the same as used in the claimed process” (Reply Br. 2). That argument is not persuasive. Although Mizzoni is directed to the preparation of specific compounds, which are not tiotropium salts, Mizzoni’s disclosure of how to convert one quaternary ammonium salt to another quaternary ammonium salt would appear to be generally applicable to other quaternary ammonium salts. That is, Mizzoni does not disclose that conversion process is designed for or specific to the Mizzoni compounds, but generically refers to quaternary ammonium salts. Appellants argue that Pfizer, Inc. v. Apotex. Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007), which was cited by the Examiner, is not applicable, because it “does not relate to a finding of obviousness for method claims … [and] pertains to obviousness of compound species when it is necessary to pick such a species out from a generic teaching” (Reply Br. 2; see also App. Br. 5-6). Appellants argue that “there is no generically encompassing teaching in any of the cited references pertinent to the claimed method here” (Reply Br. 2). Appellants’ arguments do not convince us to the otherwise. The Examiner relies on Pfizer v. Apotex only to show that optimization and Appeal 2013-006374 Application 10/976,688 9 selection of one of a known group of pharmaceutically acceptable salts is routine optimization. We agree with the Examiner’s reasoning. Appellants argue further that the Examiner’s reliance on In re Durden, 763 F.2d 1406 (Fed. Cir. 1985) was in error and that In re Ochiai, 71 F.3d 1565 (Fed. Cir. 1995) and In re Brouwer, 77 F.3d 422 (Fed. Cir. 1996) hold that “per se rules as to obviousness … are not proper and the invention must be considered as a whole, including the nature of the starting materials and [the] end product in process claims” (id. at 2). We agree with Appellants that each case must be decided on its own facts. In re Ochiai, 71 F.3d at 1571-72 and In re Brouwer, 77 F.3d at 425- 26. Here, however, the Examiner has considered the starting materials, i.e. tiotropium halide salts as ammonium halide salts, and the Examiner has considered the end products, i.e. different tiotropium halide salts. Thus, it is the facts of the case, rather than a per se rule, that provides a basis for a conclusion of obviousness. Thus, we affirm the rejection of claim 1 as being obvious in view of Banholzer, Mizzoni, and Bechtold-Peters. Claims 2, 4 and 5 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv). Appellants also argue the rejection of claim 3. Claim 3 depends from claim 1 and further requires that the solvent is acetonitrile. Appellants argue that “none of the references teach … a method to convert a tiotropium salt to a different tiotropium salt by reaction with an Ag-X … [and it is] even more clear that none of the references teach or suggest carrying out such a reaction in the presence of an acetonitrile solvent” (Appeal Br. 10). Appellants argue Appeal 2013-006374 Application 10/976,688 10 that although Banholzer discloses the use of acetonitrile, “it discloses its use for a different reaction” (id.). The Examiner responds that Banholzer discloses acetonitrile as a known solvent among others such as dimethylformamide and dimethylacetamide, and that changing from one solvent to “another solvent would be prima facie obvious to one of skill in the art” (Ans. 22). We agree with the Examiner that choosing a solvent for a process of preparing triotropium salts would have been obvious to one of ordinary skill in the art. Although, Mizzoni discloses the use of anhydrous methanol as the solvent for a process of converting a quaternary ammonium salt to another quaternary ammonium salt, Banholzer discloses that solvents are known to be interchangeable and that acetonitrile is a known solvent for use with tiotropium. Thus, it would have been obvious to one of skill in the art to substitute other suitable solvents for the anhydrous methanol disclosed in Mizzoni, when applied to tiotropium. Conclusion of Law The evidence of record supports the Examiner’s conclusion that one of skill in the art would have been motivated to apply Mizzoni’s process for converting a quaternary ammonium salt from a first anion to a second anion to the tiotropium salts of Banholzer and Bechtold-Peters to obtain tiotropium salts having alternative anions. Appeal 2013-006374 Application 10/976,688 11 II. Issue The Examiner has provisionally rejected claims 1-5 on the ground of nonstatutory obviousness-type double patenting over claims 1-16 of copending Application No. 11/424,244 (referred to herein as “the ‘244 application”) in view of Mizzoni, Banholzer, DeSilva and Bechtold-Peters. The claims have not been argued separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(iv). We thus focus our analysis on claim 1, and claims 2-5 stand or fall with that claim. The Examiner finds that the ‘244 application “teaches the conversion of a bicarbonate tiotropium to a different quaternary ammonium salt” (Ans. 16). The Examiner finds that “Mizzoni teaches a generic process of converting one quaternary salt to another” (id.). The Examiner finds that DeSilva “teaches the basis of ion exchange” (id.). The Examiner finds that Bechtold-Peters teaches that, for tiotropium salt, the “counter-ion (anion) may be chloride, bromide, iodide, methanesulphonate, para-toluene- sulphonate or methyl sulphate,” with bromide being preferred (id.). The Examiner concludes that claims 1-5 of the instant application are not patentably distinct from claims 1-16 of the ‘244 application, in view of Mizzoni, Banholzer, DeSilva and Bechtold-Peters for the reasons discussed above with respect to the obviousness rejection (id. at 16-17). Appellants argue that the Examiner erred in concluding that instant claim 1 is not patentably distinct from claims 1-16 of the ‘244 application (Appeal Br. 11-13). Appeal 2013-006374 Application 10/976,688 12 The issue presented is: Does the evidence of record support the Examiner’s conclusion that instant claim 1 is not patentably distinct from claims 1-16 of the ‘244 application when read in view of the cited secondary references? Additional Findings of Fact FF7. Claim 1 of the ’244 application reads as follows: 1. A process for preparing new tiotropium salts of formula 1 wherein X‾ is an anion which is different from HCO‾ (=bicarbonate), comprising preparing a tiotropium bicarbonate of formula 2 and reacting the tiotropium bicarbonate of formula 2 in a suitable solvent with an acid HX, wherein X‾ has the meaning above. FF8. Claim 2 of the ’244 application depends from claim 1 and further requires that X‾ “is a halide, HSO4 ‾, H2PO4 ‾ …,” among others. Principles of Law The key question in any obviousness double patenting analysis is: “Does any claim in the application define merely an obvious variation of an Appeal 2013-006374 Application 10/976,688 13 invention claimed in the patent asserted as supporting double patenting?” General Foods Corp. v. Studiengesellschaft Kohle mbH, 972 F.2d 1272, 1278 (Fed. Cir. 1992) (discussing In re Vogel, 422 F.2d 438 (CCPA 1970)). As stated by our reviewing court in In re Braat, 937 F.2d 589, 592-93 (Fed. Cir. 1991) (citation omitted): Obviousness-type double patenting is a judicially created doctrine intended to prevent improper timewise extension of the patent right by prohibiting the issuance of claims in a second patent which are not “patentably distinct” from the claims of a first patent. The analysis of an obviousness-type double patenting rejection is analogous to an obviousness analysis under 35 U.S.C. § 103(a), and comes into play during the step of determining the obviousness of the “difference” between the claimed invention and the patented invention. See Studiengesellschaft Kohle mbH v. N. Petrochemical Co., 784 F.2d 351, 355 (Fed. Cir. 1986); In re Longi, 759 F.2d 887, 892-93 (Fed. Cir. 1985). Analysis Appellants argue that instant claim 1 “does not encompass bicarbonate anions. Thus, there is no overlapping subject matter” (Appeal Br. 11). The Examiner responds that the difference between the claimed processes is that the starting anion is different, but that the process is still the inter-conversion of one salt form to another, using a known process (Ans. 24). The Examiner reasons further that Bechtold-Peters provides a reason as to why the skilled artisan would have converted one salt form to another, and thus the rejected claims are obvious over the claims of the ’244 application (id.). Appeal 2013-006374 Application 10/976,688 14 We conclude that the Examiner has not demonstrated by a preponderance of the evidence that the claims of the instant application over the claims of the ’244 application. We agree that Mizzoni teaches a process for the inter-conversion of one salt form to another. We further agree that Bechtold-Peters teaches that “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” (Bechtold- Peters at 3, ¶ 0033). What is missing, however, is scientific reasoning or evidence that the ordinary artisan would have considered the bicarbonate anion to be a known, acceptable anion. That is, the Examiner’s reasoning is solely that the process of an ion exchange in a compound that has quarternary nitrogen is known (Ans. 23), and does not address the difference in the starting compounds. We thus reverse the obviousness-type double patenting rejection. Conclusion of Law The evidence of record does not support the Examiner’s conclusion that instant claim 1 is not patentably distinct from claims 1-16 of the ’244 application when read in view of the cited secondary references. SUMMARY We affirm the rejection of claims 1-5 under 35 U.S.C. § 103(a). We reverse the provisional obviousness-type double patenting rejection of claims 1-5. Appeal 2013-006374 Application 10/976,688 15 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 cdc Copy with citationCopy as parenthetical citation