Ex Parte Banholzer et alDownload PDFPatent Trial and Appeal BoardSep 26, 201310977753 (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 2013-006375 Application 10/977,753 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 1-6 and 8-11.2 We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. 1 The Real Party in Interest is Boehringer Ingelheim International GmbH (App. Br. 1). 2 Claims 12-29 are also pending, but stand withdrawn from consideration (App. Br. 2). App App wher solva iodid hydr triflu C1-C by fl mon wher Y‾ d halid optio catio eal 2013-0 lication 10 Claim 1, 1. A pro ein X‾ den tes or hyd selected e, C1-C4-a ogen phos oroacetate 4-alkylsulp uorine at t o- or polys comprisi ein enotes an e, C1-C10- nally in th in a suita n and X h 06375 /977,753 ST the only i cess for p otes an an rates there from the g lkylsulpha phate, dihy , citrate, f honate, w he alkyl gr ubstituted ng reactin anion othe alkylsulph e form of ble solven as the sam ATEMEN ndependen reparing ti ion other of, roup cons te, sulpha drogen ph umarate, ta hich may oup, or ph by C1-C4- g a tiotrop r than X‾, onate, C1- solvates o t with an e definitio 2 T OF TH t claim on otropium s than Y‾, op isting of fl te, hydrog osphate, n rtrate, oxa optionally enylsulph alkyl at th ium salt o selected fr C10-alkyls r hydrates ion source n as X‾ ab E CASE appeal, re alts of for tionally i uoride, ch en sulphat itrate, ma late, succ be mono- onate, whi e phenyl r f formula 2 om the gro ulphate, C thereof, Kat-X, wh ove. ads as fol mula 1 n the form loride, bro e, phospha leate, acet inate and b , di- or tris ch may op ing, up consis 6-C10-aryls erein Kat lows: of mide, te, ate, enzoate, ubstituted tionally b ting of ulphonate denotes a e , Appeal 2013-006375 Application 10/977,753 3 The claims stand rejected as follows: • Claims 1-6 and 8-11 under 35 U.S.C. § 103(a) in view of Mizzoni,3 Banholzer4 and Bechtold-Peters5 (Ans. 5-14); • Claims 1-6 and 8-11 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, and Bechtold-Peters7 (Ans. 14- 16). I. Issue The Examiner has rejected claims 1-6 and 8-11 under 35 U.S.C. § 103(a) as obvious in view of Mizzoni, Banholzer and Bechtold-Peters. The Examiner finds that Banholzer teaches tiotropium bromide and a process of making it (Ans. 7). The Examiner finds that Mizzoni discloses a process of converting one quaternary ammonium salt to another (id. at 9-10). The Examiner finds that Bechtold-Peters teaches tiotropium salts in which the counter-ion (anion) may be chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate, or methyl sulphate (id. at 11). The Examiner concludes that “[b]ased on the teaching of Banholzer, Mizzoni and the teaching of Bechtold-Peters that the chloride and bromide 3 Mizzoni, 3,551,492, issued Dec. 29, 1970. 4 Banholzer et al., 6,486,321 B2, issued Nov. 26, 2002. 5 Bechtold-Peters et al., 2002/0110529 A1, published Aug. 15, 2002. 6 Application No. 11/424,244, filed Jun. 15, 2006. 7 The Examiner also cites U.S. Patent No. 6,486,321 (Ans. 15), but does not explain its relevance to the obviousness-type double patenting rejection. We thus do not address it further. Appeal 2013-006375 Application 10/977,753 4 salts are known equivalents, replacing the bromide with the chloride or other disclosed salts in Bechtold-Peters represents routine substitution of an obvious equivalent” (id. at 13). Appellants contend that the cited references would not have rendered obvious the process of claim 1 for preparing tiotropium salts because the ordinary artisan 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. 5-6). 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.) Banholzer also discloses a process for preparing tiotropium bromide (id. at col. 1, ll. 12-15). Appeal 2013-006375 Application 10/977,753 5 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). 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). FF5. Bechtold-Peters discloses that 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). FF6. 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). Appeal 2013-006375 Application 10/977,753 6 FF7. 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). FF8. Mizzoni discloses that “quaternary ammonium compounds may be converted itno [sic] other quaternary ammonium compounds, such as the quaternary ammonium hydroxides, for example, by reacting a quaternary ammonium halide with silver oxide, or a quaternary ammonium sulfate with barium hydroxide” (id. at col. 4, ll. 20-25). 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). Appeal 2013-006375 Application 10/977,753 7 Analysis Claim 1 is directed to a process for preparing tiotropium salts having an anion X by reacting a tiotropium salt having an anion Y with an ion source, Kat-X, in a suitable solvent. Claim 1 also requires that anion X is different from anion Y and is selected from the group consisting of, among other things, fluoride, chloride, bromide and iodide. Claim 1 also requires that anion Y is selected from the group consisting of halide, C1-C10 alkylsulphonate, C1-C10-alkylsulphate, C6-C10-arylsulphonate. Claim 1 also requires that, for Kat-X, Kat denotes a cation and X has the same definition as 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 converted into another quaternary ammonium salt, when reacted with silver chloride, to yield quaternary ammonium chloride. Thus, we agree with the Examiner that 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. Appeal 2013-006375 Application 10/977,753 8 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 “Bechtold-Peters … merely indicates the existence of optional tiotropium salts,” but not methods to convert one to the other (id.). This argument is not persuasive. The cited references provide evidence that all of the elements of claim 1 are known, i.e. the usefulness of different salts for tiotropium, as well as 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. Appellants argue that “Mizzoni’s teachings are limited to N,N’ - aralkyl-alkylenediamines” (Reply Br. 2). 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” (id.). This 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 Appeal 2013-006375 Application 10/977,753 9 quaternary ammonium salt would appear to be generally applicable to other quaternary ammonium salts. In that regard, we note that Mizzoni does not disclose that conversion process is designed for or specific to the Mizzoni compounds. 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). Appellants argue that “[t]here is no generically encompassing teaching in any of the cited references pertinent to the claimed method here” (id.). This argument is not persuasive. The Examiner relies on Pfizer v. Apotex only to show that optimization and selection of one of a known group of pharmaceutically acceptable salts is routine optimization. We agree with the Examiner’s reasoning. Appellants argue 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). This argument is not persuasive. 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. However, here the Examiner has considered the starting materials, i.e. tiotropium halide salts as ammonium Appeal 2013-006375 Application 10/977,753 10 halide salts, and 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 4-6 and 8-11 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv). Appellants also separately argue the rejection of claims 2 and 3. Specifically, Appellants argue that “[n]one of the references teach … a method to convert a tiotropium salt to a different tiotropium salt by reaction with a Kat-X salt where the cation, Kat, is selected from … alkali or alkaline earth metals, ammonium (NH4+) or tetralkylammonium (N(C1-C8-alkyl)4+)” (Appeal Br. 10). As the Examiner has not addressed claims 2 and 3, we reverse the rejection. 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. We thus affirm the rejection as to claims 1, 4-6, and 8-11. As the Examiner has not addressed claims 2 and 3, we reverse the rejection as to those claims. Appeal 2013-006375 Application 10/977,753 11 II. Issue The Examiner has provisionally rejected claims 1-6 and 8-11 on the ground of nonstatutory obviousness-type double patenting over claims 1-16 of copending Application No. 11/424,244 in view of Mizzoni, Banholzer, 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 2-6 and 8-11 stand or fall with that claim. The Examiner finds that the ’244 application teaches the conversion of a “bicarbonate salt to another salt which can be halide, sulphate, phosphate” and others (Ans. 15). The Examiner finds that Mizzoni teaches a “process of converting a quaternary ammonium salt … to a halide or another salt” (id.). The Examiner finds that “the Bechtold-Peters reference provides a reason to alter the anion of the tiotropium salt using the process as given in Mizzoni to obtain the tiotropium salts as required by claim 1” (id. at 16). 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). 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 secondary references? Appeal 2013-006375 Application 10/977,753 12 Additional Findings of Fact FF9. 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 HCO3‾ (=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. FF10. 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 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)). Appeal 2013-006375 Application 10/977,753 13 As stated by our reviewing court in In re Braat, 937 F.2d 589, 592 (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. An analysis analogous to an obviousness analysis under 35 U.S.C. § 103(a) 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.). 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 Appeal 2013-006375 Application 10/977,753 14 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. 24), 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. SUMMARY We affirm the rejection of claims 1, 4-6 and 8-11 under 35 U.S.C. § 103(a), and reverse the rejection as to claims 2 and 3. We also reverse the provisional rejection of claims 1-6 and 8-11 as being unpatentable due to obviousness-type double patenting. Appeal 2013-006375 Application 10/977,753 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-IN-PART cdc Copy with citationCopy as parenthetical citation