Wilhelm Wurst et al.Download PDFPatent Trials and Appeals BoardOct 29, 201911578294 - (D) (P.T.A.B. Oct. 29, 2019) 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. 11/578,294 11/02/2006 Wilhelm Wurst 36217-303 9741 28221 7590 10/29/2019 PATENT DOCKET ADMINISTRATOR LOWENSTEIN SANDLER LLP ONE LOWENSTEIN DRIVE ROSELAND, NJ 07068 EXAMINER DRAPER, LESLIE A ROYDS ART UNIT PAPER NUMBER 1629 NOTIFICATION DATE DELIVERY MODE 10/29/2019 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): patents@lowenstein.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte WILHELM WURST, THOMAS BETHKE, and RENATE ENGELSTATTER Appeal 2018-007887 Application 11/578,294 Technology Center 1600 ____________ Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and RYAN H. FLAX, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL The claims in this appeal are directed to methods of treating coronary obstructive pulmonary disease with ciclesonide. The Examiner rejected the claims under 35 U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134, Appellant1 appeals the Examiner’s determination that the claims are unpatentable. We have jurisdiction for the appeal under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as AstraZeneca AB. Appeal Br. 3. Appeal 2018-007887 Application 11/578,294 2 STATEMENT OF CASE The claims are directed to methods of administering ciclesonide to treat chronic obstructive pulmonary disease (“COPD”). Ciclesonide is a glucocorticosteroid that the Specification discloses is used to treat asthma. Specification 1–2. Claims 1, 7, 8, 12, 13 and 18–26 stand finally by the Examiner under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Persson et al. (WO 99/53926 A1, published Oct. 28, 1999) (“Persson”), Oliver et al. (U.S. Patent No. 6,264,923 B1, issued Jul. 24, 2001) (“Oliver”), and Dent (“Ciclesonide - Byk Gulden,” Curr. Op. Inv. Drugs, 2002, 3(1):78-83). Ans. 3; Final Act. 3. Independent claim 1, which is representative, is reproduced below: 1. A method for treating COPD in a smoking patient comprising administering to the patient in a continuous treatment regimen of twelve weeks or more a therapeutically effective and pharmacologically tolerable dose of a composition comprising ciclesonide, or a pharmaceutically acceptable salt thereof dissolved in a pharmaceutically acceptable carrier, wherein the dose comprises 20 to 200 μg ciclesonide and the dose is a daily dose, wherein the composition is suitable for administration by inhalation, wherein the composition is a pharmaceutical aerosol formulation comprising a therapeutically effective amount of ciclesonide and a hydrofluorocarbon propellant, and cosolvent in an amount effective to solubilize ciclesonide and optionally a surfactant. REJECTION The Examiner found that Persson discloses treating a patient with chronic obstructive pulmonary disease (“COPD”) with a glucocorticosteroid, and specifically discloses ciclesonide among a list of glucocorticosteroids. Appeal 2018-007887 Application 11/578,294 3 Final Act. 3. Ciclesonide is the same compound recited in claim 1. Persson also discloses that the patients with COPD are smokers, meeting the claimed requirement of “treating COPD in a smoking patient.” Id. The Examiner also found that Persson disclose treating COPD for a least a year with the glucocorticosteroid, which is “a continuous treatment regimen of twelve weeks or more” as recited in claim 1. Id. The claim recites that the dose of ciclesonide, the claimed glucocorticosteroid, is a “daily dose” of “20 to 200 μg.” The Examiner found that Persson discloses the glucocorticosteroid is administered by inhalation and “preferably in an amount of 100-2000 μg per dose (p. 6, lines 25-30; claim 23), which overlaps the range of 20-200 μg recited by claim 1.” Final Act. 3–4. Claim 1 also recites that “composition” is administered by inhalation and “is a pharmaceutical aerosol formulation comprising a therapeutically effective amount of ciclesonide and a hydrofluorocarbon propellant.” The Examiner found that Persson discloses administering the glucocorticosteroid by inhalation as a composition comprising a liquid propellant, including the same propellant recited in dependent claims 21 and 22. Final Act. 4. The Examiner found that, although Persson does not specifically exemplify treating a COPD patient with ciclesonide, Dent specifically teaches treating COPD with ciclesonide and at a dose of 200 μg, which overlaps with the claimed dose of 20–200 μg. Final Act. 4–5. The Examiner further cited Oliver for disclosing the claimed “pharmaceutical aerosol formulation comprising a therapeutically effective amount of ciclesonide and a hydrofluorocarbon propellant, and cosolvent.” Final Act. 4. Appeal 2018-007887 Application 11/578,294 4 DISCUSSION Ciclesonide Appellant contends that “Persson mentions ciclesonide only as one of over 20 options for choice of a glucocorticosteroid to treat mild or early COPD, focusing on ‘most preferable’ budesonide and providing no reason to choose ciclesonide.” Appeal Br. 11. This argument is not persuasive. Appellant expressly admits that ciclesonide is disclosed by Persson. The fact that ciclesonide appears in a list is not any less a disclosure of it. “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put into the last opening in a jig-saw puzzle. It is not invention.” Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 335 (1945). Indeed, a species that is specifically disclosed in a prior art reference is anticipatory even though it appears “without special emphasis in a longer list.” Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1376 (Fed. Cir. 2005). Moreover, as found by the Examiner, and not challenged by Appellant, Dent discloses treating COPD with ciclesonide, the same indication and compound recited in claim 1. Treatment regimen Claim 1 recites that the patient is administered ciclesonide for “a continuous treatment regimen of twelve weeks or more.” The Examiner relied on Persson for disclosing a duration of therapy which meets this claim limitation. Ans. 4. Appellant admits that Persson discloses treating COPD patients, but states that Persson teaches that the formulation must be Appeal 2018-007887 Application 11/578,294 5 administered for at least a year “before any effect can be determined.” Appeal Br. 12. This argument is not persuasive. Persson teaches that “[a] treatment period of at least one year is necessary.” Persson 5:11. However, claim 1 requires treatment of twelve weeks or more, and one year of treatment meets this limitation. Appellant separately argues independent claim 23, which recites “a continuous treatment regimen of one to twelve weeks” and contends it “inherently” requires “therapeutic efficacy within twelve weeks.” Appeal Br. 9 (fn. 1). Appellant also separately argues claims 25 and 26 which recite “wherein the continuous treatment regimen begins to provide the therapeutic efficacy within twelve weeks.” Appeal Br. 9. Appellant argues that these limitations are not described by Persson because Persson teaches that a year of treatment is necessary. Appeal 12. We are not persuaded by these arguments. Persson expressly teaches that treatment with the glucocorticosteroid, budesonide, showed a “Linear Change Over Time.” See Persson, legends to Figs. 1–4; 4:12–16. Figure 2 of Persson is reproduced below: Appeal 2018-007887 Application 11/578,294 6 Figure 2 of Persson, reproduced above, shows the effect of the glucocorticosteroid budesonide over time on the lung function of smokers with COPD. The solid line is treatment with budesonide and the dotted line is the placebo without budesonide. Lung function was measured by FEV, which is forced expiratory volume in 1 second. Persson 3:24. The starting “visit,” when measurements begins, is shown at “3.” The FEV value (FEV1 or FEV1) was determined in subsequent visits to the medical center at “approximately every 2–3 months.” Persson 9:9–12, 17–18 (visits numbered consecutively 1–15 in Figure 2). At each visit, numbered 3 to 15, the measured FEV shows an incremental and linear decline in the FEV over time, indicating that the treatment with the glucocorticosteroid. Figure 2 shows that at visit 4, which was at 8 weeks (2 months) to 12 weeks (3 months), there is a smaller decline in lung function as measured by FEV in patients treated with the glucocorticosteroid (solid line) than in untreated patients (dotted line). Figure 2 therefore expressly shows that “therapeutic efficacy within twelve weeks,” as required by claims 23, 25, and 26, is observed with continuous treatment of the glucocorticosteroid. Appeal 2018-007887 Application 11/578,294 7 Appellant acknowledges these results, but states “no statistical data [is] reported, so real significance is not available at all” and contend that “Persson interprets the Figures to indicate that a “treatment period of at least one year is necessary.” Reply Br. 8. We do not agree. First, as noted by the Examiner, the claims do not require a specific degree of therapeutic efficacy. Ans. 17. Second, while Persson states that a “treatment period of at least one year is necessary” for the glucocorticosteroid (Persson 5:11), Persson does not state that no therapeutic efficacy is observed before this year period and Persson expressly says that the change in FEV is “Linear Change Over Time” (legend to Figs. 1–4), indicating therapeutic efficacy throughout the entire time period. It is unreasonable to interpret Persson as teaching that a full year of treatment with the glucocorticosteroid is necessary before any effect is observed, and then on that one year date, suddenly clinical efficacy is observed. This unreasonable interpretation of Persson is also inconsistent with the data reported by Persson in Figure 2. Dosage Appellant contends that “[t]o the extent Dent reports results of Phase II clinical trials, they typically relate to studies using higher than presently- claimed doses of ciclesonide, administered for less severe conditions than COPD.” Appeal Br. 13. Based on these dosages, Appellant contends that “if anything, the prior art would support a conclusion that for treating COPD, as compared with ‘mild to moderate’ asthma, for example, Appeal 2018-007887 Application 11/578,294 8 substantially higher daily doses than 200 μg would be required to have any real chance of providing effective relief to the patient.” Id. We begin by identifying the relevant disclosures in Dent. Dent has the following pertinent teachings (labeled as Findings of Fact or “FF”): FF1. Dent teaches that ciclesonide is “being developed by Byk Gulden for chronic obstructive pulmonary disease” and that Phase III trials are being carried out, but no results are yet available. Dent ¶ 78. FF2. Dent teaches that, in a Phase II trial with mildly asthmatic patients, both ciclesonide and budesonide at the same dosage of 400 µg/day “are equally effective in reducing airway inflammation and bronchial responsiveness.” Dent ¶ 80. FF3. Dent also teaches that in a Phase II study “Ciclesonide (200 µg by one-daily inhalation), morning or evening, for 8 weeks in 168 mild-to- moderate asthmatic patients led to significantly improved asthma control.” Dent ¶ 80. FF4. Dent teaches that “inhaled glucocorticosteroids exhibit a certain degree of efficacy in COPD and other airway diseases.” Dent ¶ 80. FF5. Dent also discloses: Clinical trials are also underway to assess the value of ciclesonide in the treatment of COPD a condition to which the contribution of airway inflammation is variable and in which the therapeutic value of corticosteroids is debated. The results of these trials are not yet available. Dent ¶ 81. Dent does not disclose the dosage of ciclesonide to be administered in the clinical trials (FF1, FF5). However, Dent discloses, as admitted by Appellant, that ciclesonide and budesonide were equally effective in treating airway inflammation in asthmatics at a dose 400 µg/per day (FF2), and that Appeal 2018-007887 Application 11/578,294 9 200 µg/day of ciclesonide led to significant improvement in asthma control (FF3), providing a rationale for picking this lower dosage to treat COPD in a clinical trial. See Ans. 13. Thus, even if Persson uses higher doses of budesonide to treat asthma as stated by Appellant (“Persson unequivocally concludes that even with 800 μg daily, treatment requires at least one year, and preferably three years.” Reply Br. 12), Dent provides reason to use lower doses of ciclesonide in COPD since lower doses (200 µg by one-daily inhalation) were found to be effective in the treatment of asthmatics.2 Appellant argues that “if ciclesonide even could be used to provide substantial relief from COPD, it would likely be at a substantially higher dose, rather than at a lower one.” Appeal Br. 14. However, the claims do not require “substantial relief,” and as indicated above, Dent teaches that a dose of that 200 µg/day of ciclesonide can be used to treat asthma (FF3), providing a reasonable expectation that such dosage could also treat COPD because both involve airway inflammation (FF2, FF5). See also the Examiner’s well-reasoned discussion in the Answer on page 8–9 finding that Dent and Persson establish the functional equivalency of budesonide and ciclesonide in having anti-inflammatory activity in treating airways diseases. Moreover, as found by the Examiner, Persson discloses an overlapping dosage range, making it obvious to optimize to find an effective amount. Persson specifically teaches: 2 The Specification also discloses a 2003 publication that reported “a trend” in FEV “for the superiority of ciclesonide over budesonide” in asthma patients (Specification 2 (second full paragraph), indicating that less ciclesonide might be needed compared to budesonide. This is the same result shown in Example 2 of the Specification, namely, a lower dosage of ciclesonide was needed as compared to budesonide. Appeal 2018-007887 Application 11/578,294 10 FF6. The amount of glucocorticosteroid administered to the patient is preferably from 100 μg to 3000 μg per day, more preferably from 200μg to 1600 μg administered, as a single or divided dose/s one to four times per day. Persson 6:20–22. While Dent states that the value of corticosteroids is “debated” (Appeal Br. 13), at the same time Dent teaches that “inhaled glucocorticosteroids exhibit a certain degree of efficacy in COPD” (FF4) and therefore conduct a clinical trial to assess its value in the treatment of COPD (FF5). One of ordinary skill in the art would have had a reasonable expectation of success that ciclesonide would be useful to treat COPD for several reasons. First, Dent teaches that ciclesonide treats airway inflammation and airway inflammation occurs in COPD (FF2, FF5). Second, as discussed above (see discussion of Figure 2), Persson established that budesonide, a glucocorticosteroid, is effective in treating COPD. Ciclesonide is also a glucocorticosteroid. FF7. Persson discloses: The successful result of the treatment of mild COPD with glucocorticosteroids has been demonstrated in the present invention by the treatment of a large group of patients during a period of three years. The patients were chosen to fulfill the criteria of mild COPD as set out above and they were all smokers. The results of the clinical trials show that early use of a glucocorticosteroid in mild/early COPD will improve the patients situation considerably i.e. the progressive course of the disease has been significantly decreased by the treatment. Persson 4:22–29. Appeal 2018-007887 Application 11/578,294 11 FF8. Persson further discloses: The glucocorticosteroid used in the invention is preferably an anti-inflammatory glucocorticosteroid. Among the glucocorticosteroids which can be used for the manufacture of the medicaments according to the present invention the following can be mentioned: betamethasone (e.g. as valerate), fluticasone (e.g. as propionate), budesonide, tipredane, dexamethasone, beclomethasone (e.g. as dipropionate), prednisolone fluocinolone, triamcinolone (e.g. as acetonide), mometasone (e.g. as furoate), rofleponide (e.g. as palmitate), flumethasone, flunisolide, ciclesonide, . . . . Persson 5:14–20. Thus, the evidence establishes that Persson describes the efficacy of glucocorticosteroids in treating COPD (FF7), providing a reasonable expectation of success that the ciclesonide, specifically disclosed in Persson (FF8), would be effective in the treatment of such patients. Appellant also argues that “[t]here is no express consideration in Persson of treating COPD with ciclesonide at all, much less what effect there may be on the required dose, duration, or anticipation of efficacy in treating COPD.” Reply Br. 7. Persson teaches that glucocorticosteroids are useful to treat COPD smokers, the same class of patients as claimed. FF7. Ciclesonide is listed as an example of a glucocorticosteroid, which is the same compound which is claimed. FF8. Ciclesonide is not used in Persson’s working examples, but, as explained by the Examiner: The fact that Persson et al. exemplifies budesonide in the treatment of COPD is immaterial because a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. MPEP § 2123(1) (citing Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Appeal 2018-007887 Application 11/578,294 12 Cir.), cert. denied, 493 U.S. 975 (1989)). Disclosed examples and preferred embodiments (in this case, Persson's exemplified budesonide) does not constitute a teaching away from a broader disclosure or nonpreferred embodiments. MPEP §2123(11) (citing In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971)). Ans. 8. Specification evidence Appellant contends that the Specification provides additional evidence supporting the claims. Appeal Br. 15. Appellant states: Example 2 reports statistically significant improvements from 12-week treatments with 200 μg ciclesonide regarding pulmonary function and asthma symptoms specifically in the group of patients who were ex-smokers - despite the lack of demonstrated improvement with even twice as much budesonide, 400 μg daily Specification as filed, at pages 8, 9. Nothing in the prior art suggests such a low dose of ciclesonide as compared to budesonide is capable of providing this unexpected benefit in smokers or ex-smokers. Appeal Br. 16. This evidence is not persuasive. As discussed by the Examiner, the example is directed to a different class of patients than claimed, namely patients with asthma, rather than the treatment of smoking patients with COPD. Thus, as the Examiner clearly explained: Appellant’s characterization [on Appeal br. 10, 14], therefore, of Ex.2 as providing evidence of “superior, unexpected results in the claimed patient population with ciclesonide” is clearly false - Ex.2 is not directed to the “claimed patient population”. It is directed to administration of ciclesonide to asthmatic subjects, not smoking patients with COPD. As such, Appellant's Ex.2 is not clearly germane to the claimed method as it is directed to a wholly distinct patient population and, Appeal 2018-007887 Application 11/578,294 13 therefore, is not commensurate in scope with the claims which the evidence is offered to support. Ans. 15. In addition, we agree with the Examiner’s analysis that, even if Example 2 were considered relevant to the claimed method, “the data is limited to a specific once daily inhalation of 200 μg ciclesonide, which fails to clearly support the entirety of the daily dose range of 20-200 μg ciclesonide instantly claimed.” Ans. 15. Summary In view of the foregoing, we conclude that a preponderance of the evidence supports the Examiner’s determination that claims 1, 23, 25, and 26 are obvious in view of Persson, Oliver, and Dent. Claims 7, 8, 12, 13, and 18–22, and 24 were not argued separately and fall with claims 1 and 23. 37 C.F.R. § 41.37(c)(1)(iv). Appeal 2018-007887 Application 11/578,294 14 DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § References(s)/Basis Affirmed Reversed 1, 7, 8, 12, 13, 18–26 103 Persson, Oliver, Dent 1, 7, 8, 12, 13, 18–26 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED Copy with citationCopy as parenthetical citation