Ex Parte Berkel et alDownload PDFPatent Trial and Appeal BoardMar 1, 201611668123 (P.T.A.B. Mar. 1, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 11/668,123 01129/2007 75410 7590 03/03/2016 Micheal P, Morris Boehringer Ingelheim USA Corporation 900 Ridgebury Road Ridgefield, CT 06877-0368 FIRST NAMED INVENTOR Erhard Berke! 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 01-2014 3291 EXAMINER HAGHIGHATIAN, MINA ART UNIT PAPER NUMBER 1616 NOTIFICATION DATE DELIVERY MODE 03/03/2016 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): USPTO.e-Office.rdg@boehringer-ingelheim.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ERHARD BERKEL, HUBERT HOELZ, and FRIEDRICH SCHMIDT Appeal2013-007050 Application 11/668, 123 Technology Center 1600 Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and JACQUELINE T. HARLOW, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal 1 under 35 U.S.C. § 134 involving claims to a pharmaceutical preparation for propellant-driven metered-dose aerosols. The Examiner rejected the claims as obvious and on the grounds of obviousness-type double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellants identify the Real Parties in Interest as Boehringer Ingelheim International GMBH (see App. Br. 2). Appeal2013-007050 Application 11/668, 123 Statement of the Case Background "The present invention relates to new pharmaceutical formulations for aerosols with at least two or more active substances together with at least one surfactant for inhalative or nasal application" (Spec. 1, 11. 8-10). The Claims Claims 1-14, 21, 23, and 30 are on appeal. Independent claim 1 is representative and reads as follows: 1. A pharmaceutical preparation for propellant-driven metered-dose aerosols having a fluorinated hydrocarbon (HF A) as propellant, which contains a combination of two or more active substances, wherein at least one active substance is present in dissolved form as well as at least one other active substance in the form of suspended particles together with at least one surfactant, the active substance present in dissolved form being ipratropium bromide monohydrate, the active substance present in the form of suspended particles being salbutamol sulphate ( albuterol sulphate), the surfactant being polyoxyethyleneglycerol trioleate, wherein the preparation does not contain water, wherein the surfactant is present in a concentration of 0.02% - 0.2% based on the mass of surfactant/mass of the formulation as a whole (m/m). The Issues A. The Examiner rejected claims 1-14, 21, 23, and 30 under 35 U.S.C. § 103(a) as obvious over McNamara '2982 and Chen3 (Ans. 6-8). B. The Examiner rejected claims 1-14, 21, 23, and 30 under 35 U.S.C. § 103(a) as obvious over McNamara '4644 and Geller5 (Ans. 8-10). 2 McNamara et al., US 6,423,298 B2, issued July 23, 2002. 3 Chen et al., US 2004/0092428 Al, published May 13, 2004. 2 Appeal2013-007050 Application 11/668, 123 C. The Examiner rejected claims 1-14, 21, 23, and 30 under 35 U.S.C. § 103(a) as obvious over Lulla,6 McNamara '464, and Chen (Ans. 10-13). D. The Examiner rejected claims 1-14, 21, 23, and 30 on the ground of nonstatutory obviousness-type double patenting over claims 1-21 of US 6,423,298 and Chen (Ans. 14--15). Because the same issues are dispositive for all of the rejections, we will consider the rejections together. The Examiner relies upon McNamara '298, McNamara '464, or the claims of McNamara '298 to teach pharmaceutical aerosols comprising salbutamol suspensions with dissolved ipratropium bromide that include a poyoxyethylene surfactant (Ans. 6; cf Ans. 8, 14). The Examiner acknowledges that these references "lack[] disclosure on the specific species of polyoxyethylenes" (Ans. 7, 9) and relies on Chen, Geller, or Lulla to suggest the polyoxyethyleneglycerol trioleate surfactant in pharmaceutical formulations including aerosols (Ans. 7; cf Ans. 9, 11, 15). The Examiner finds the "motivation for substituting them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose" (Ans. 7; cf Ans. 10, 12, 15). The issue with respect to these rejection is: Does the evidence of record support the Examiner's conclusion that the prior art renders the claims obvious? 4 McNamara et al., WO 99/65464 Al, published Dec. 23, 1999. 5 Geller et al., US 3,632,743, issued Jan. 4, 1972. 6 Lulla et al., WO 2004/019985 Al, published Mar. 11, 2004. 3 Appeal2013-007050 Application 11/668, 123 Findings of Fact 1. McNamara '298 teaches "stable aerosol formulations with fluorohydrocarbons as propellants, particularly TG 134a and/or TG 227, consisting of two or more active substances, wherein at least one active substance is formulated as a solution and at least one active substance is formulated as a suspension" (McNamara '298, col. 2, 11. 21-26; McNamara '298, col. 4, claims 1, 3; cf McNamara '464 3, 11. 30-35). 2. McNamara '298 teaches that a "preferred embodiment contains dissolved ipratropium bromide, particularly combined with salbutamol sulphate (albuterol sulphate) as the suspended active substance" (McNamara '298, col. 2, 11. 60-63; McNamara '298, col. 6, claim 21; cf McNamara '464 4, 1. 35 to 5, 1. 2). 3. McNamara '298 teaches that "[s]uitable surfactants and suspension-stabilising agents include ... polyoxyethylenes ... The quantity of surfactant may be up to 1: 1 based on the proportion by weight of the suspended active substances; amounts of0.0001:1to0.5:1 are preferred, whilst amounts of from 0.0001:1to0.25:1 are particularly preferred" (McNamara '298, col. 3, 11. 16-36; McNamara '298, col. 5, claim 14; cf McNamara '464 5, 1. 27 to 6, 1. 12). 4. Example 1 of McNamara '298 teaches the inclusion of"0.05% by weight of surfactant" of oleic acid in a solution comprising the propellant TG 134a, dissolved ipratropium bromide, and suspended salbutamol sulphate (McNamara '298, col. 4, 11. 23-30; cf McNamara '464 8, 11. 5-12). 4 Appeal2013-007050 Application 11/668, 123 5. Lulla teaches "a pharmaceutical composition comprising any one of the following combinations of therapeutic agents ... (ix) salbutamol, budesonide and ipratropium" (Lulla 3). 6. Lulla teaches "a propellant-containing dosage aerosol ... the formulation may consist of a surface-active agent to stabilize the formulation .... Preferred surfactants for use ... [include] oleic acid ... sorbitol trioleate .... the surface-active agents are preferably used in the formulations in the ratio of 0.00002 wt% ... to 20 wt% of the active ingredients" (Lulla 5). 7. Example 21 of Lulla teaches a pharmaceutical composition comprising salbutamol, ipratropium, and 0.02% of the surfactant oleic acid with the propellant HFA134a (see Lulla 18). 8. Chen teaches "a pharmaceutical formulation capable of being administered orally as discrete pharmaceutical unit dosage forms, each containing a predetermined amount of the active ingredients, such as ... aerosols sprays" (Chen i-f 60). 9. Chen teaches that "'surfactant of the invention' refer to a compound including, but not limited to ... oleic acid ... Tagat TO (polyoxyethylene glycerol trioleate )" (Chen i-f 45). 10. Chen teaches that the "pharmaceutical formulation comprises about 5% to about 90% by volume of surfactant" (Chen i-f 82). 11. Geller teaches that "[ s ]uitable non-aqueous suspending agents or solvents are those which are pharmacologically acceptable ... such as oleic acid esters ... 'Labrafil M 2735' ... 'Labrafil M 2735' is polyoxyethylene-glycerol trioleate" (Geller, col. 1, 11. 35---69). 5 Appeal2013-007050 Application 11/668, 123 Principles of Law "[W]hen a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result". KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416-417 (2007). 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 (CCP A 1982). Analysis We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art (Ans. 6-13; FF 1-10). We address Appellants' arguments below. Appellants contend that "Chen does not disclose that the concentration of polyoxyethylene glycerol trioleate can be below 5%, which is more than an order of magnitude greater than the upper limit of the claimed range" (Br. 5). Appellants contend that the "formula of Geller includes suspending agents at a very high concentration, specifically, the combination of Miglyol and benzyl alcohol in examples 3 and 4 is 18.6% and 19.9% respectively, by mass" (Br. 5). We do not find these arguments persuasive because they fail to combine the teachings of Chen and Geller with the teachings of McNamara '298, McNamara '464, or Lulla. The primary references, McNamara '298, McNamara '464, and Lulla, each teach surfactant ranges that fully overlap the claimed range of 0.2% to 0.2% (FF 3, 6) for specific pharmaceutical preparations that include the combination of salbutamol and ipratropium 6 Appeal2013-007050 Application 11/668, 123 (FF 2, 5). Moreover, McNamara '298 and McNamara '464 exemplify 0.5% surfactant (FF 4) while Lulla exemplifies 0.02% surfactant (FF 7), both values within the claimed range. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003)(" In cases involving overlapping ranges, we and our predecessor court have consistently held that even a slight overlap in range establishes a prima facie case of obviousness.") We agree with the Examiner that the ordinary artisan would have reasonably selected surfactant concentrations from the ranges and examples of McNamara '298, McNamara '464, and Lulla for surfactants in aerosols of salbutamol and ipratropium (FF 3, 6), when using known equivalent surfactants such as the polyoxyethylene glycerol trioleate surfactant disclosed by Chen or Geller (FF 9, 11). See In re Keller, 642 F.2d 413, 425 ( CCP A 19 81) ("The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference . . . . Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art.") Appellants contend that "[b ]ecause of the significant difference in amounts of surfactant used, a person of ordinary skill in the art considering Chen would not think that such a drastic modification would result in a formulation that could still effectively deliver active agents to a nasal cavity" (Br. 5). Appellants contend that the "Office Action has not considered the portions of Chen and Geller that definitively lead a person of ordinary skill in the art away from including the surfactant polyoxyethylene glycerol trioleate in a concentration of 0.02% - 0.2%" (Br. 7). 7 Appeal2013-007050 Application 11/668, 123 We find this argument unpersuasive because McNamara '298, McNamara '464, and Lulla each teach selection of surfactant amounts overlapping the claimed range for metered-dose aerosol delivery of the specific agents required by claim 1 (FF 1-7). Appellants do not identify any teaching that criticizes, discourages, or discredits the use of surfactants in the amounts disclosed by McNamara '298, McNamara '464, and Lulla. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) ("The prior art's mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed"). Instead, Appellants simply identified specific embodiments in Chen or Geller. However, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971). Here, the general embodiments of Chen and Geller do not teach away from the very specific disclosures of metered-dose aerosol delivery by McNamara '298, McNamara '464, and Lulla. Appellants contend that "[b ]ased on the Office Actions reasoning, any reference at all that states polyoxyethylene glycerol trioleate is a surfactant, would render the present claim unpatentable in view of McNamara '298. This position is untenable and contrary to law" (Br. 6). We disagree. The Examiner is not relying on any reference teaching polyoxyethylene glycerol trioleate, but rather on Chen's teaching that this surfactant is a known equivalent surfactant that may be used in pharmaceutical aerosol sprays (FF 8-9) and on Geller' s teaching that this 8 Appeal2013-007050 Application 11/668, 123 surfactant is a known equivalent that is pharmacologically acceptable (FF 11). Indeed, the Examiner specifically recognizes the equivalence of "surfactants such as poloxyethylenes and oleic acid" (Ans. 9), a finding well supported by the teaching of oleic acid as a surfactant in each of the prior art references (FF 4, 6, 9, 11) and the specific inclusion of both oleic acid and polyoxyethylene glycerol trioleate as equivalent surfactants in Chen and Geller (FF 9, 11 ). See Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356, 1364 (Fed. Cir. 2012) ("This case presents a strong case of obviousness based on the prior art references of record. [The claim] recites a combination of elements that were all known in the prior art, and all that was required to obtain that combination was to substitute one well-known ... agent for another.") Appellants contend that the "Office Action does not proffer, since there is no reasonable expectation of success, why a skilled artisan would expect that combining the primary references with the secondary references and then drastically reducing the surfactant concentrations would result in a successful pharmaceutical preparation" (Br. 7). We are not persuaded. McNamara '298, McNamara '464, and Lulla provide a very reasonable expectation of success in formulating salbutamol, ipratropium and a surfactant where the surfactant falls within their disclosed concentration ranges (FF 3, 6) or the 0.05% specific value disclosed by McNamara '298 McNamara '464 (FF 4) or the 0.02% specific value disclosed by Lulla (FF 7). Chen and Geller provide a reasonable expectation of success is using polyoxyethylene glycerol trioleate in pharmaceutical 9 Appeal2013-007050 Application 11/668, 123 preparations such as those of McNamara '298, McNamara '464, and Lulla (FF 1-11 ). This reasoning is consistent with Kubin, which stated that "[r]esponding to concerns about uncertainty in the prior art influencing the purported success of the claimed combination, this court [in O'Farrell] stated: ' [ o ]bviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success."' In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O'Farrell, 853 F.2d 894, 903- 904 (Fed. Cir. 1988)). Conclusion of Law The evidence of record supports the Examiner's conclusion that the prior art renders the claims obvious. SUMMARY In summary, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as obvious over McNamara '298 and Chen. Claims 2-14, 21, 23, and 30 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). We affirm the rejection of claim 1under35 U.S.C. § 103(a) as obvious over McNamara '464 and Geller. Claims 2-14, 21, 23, and 30 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). We affirm the rejection of claim 1under35 U.S.C. § 103(a) as obvious over Lulla, McNamara '464, and Chen. Claims 2-14, 21, 23, and 30 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). We affirm the rejection of claim 1 on the ground of nonstatutory obviousness-type double patenting over claims 1-21 of US 6,423,298 and Chen. Claims 2-14, 21, 23, and 30 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). 10 Appeal2013-007050 Application 11/668, 123 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 11 Copy with citationCopy as parenthetical citation