Ex Parte Abel et al

Patent Trial and Appeal BoardDec 17, 2012

10570986 (P.T.A.B. Dec. 17, 2012)

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. 10/570,986 03/28/2006 Florian Abel 27232U 7260 34375 7590 12/17/2012 NATH & ASSOCIATES PLLC 112 South West Street Alexandria, VA 22314 EXAMINER HUI, SAN MING R ART UNIT PAPER NUMBER 1629 MAIL DATE DELIVERY MODE 12/17/2012 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte FLORIAN ABEL, ANTJE BRUECK, KLAUS DIETZEL, KLAUS EISTETTER, RUEDIGER NAVE, STEFAN POSTIUS, and OLIVER VON RICHTER __________ Appeal 2011-004441 Application 10/570,986 Technology Center 1600 __________ Before ERIC GRIMES, FRANCISCO C. PRATS, and SHERIDAN K. SNEDDEN, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims to a method of treating inflammatory bowel disease. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE Claims 7-23 stand rejected and appealed (App. Br. 5). Appellants do not argue the claims separately, so they stand or fall together. See 37 C.F.R. § 41.37(c)(1)(vii). Claim 13 is representative and reads as follows: Appeal 2011-004441 Application 10/570,986 2 13. A method of treatment of inflammatory bowel disease in a patient comprising administering a therapeutically effective amount of ciclesonide to the patient in need thereof. The sole rejection before us for review is the Examiner’s rejection of claims 7-23 under 35 U.S.C. § 103(a) as obvious over Calatayud, 1 Ulmius, 2 Friend, 3 and Wright 4 (Ans. 4-6). DISCUSSION The Examiner found that Calatayud taught ciclesonide, the compound administered in the method of claim 13, “in the form of racemic mixtures or epimers, as a glucoc[o]rticoid and as useful in treating inflammatory condition[s]” (Ans. 4). The Examiner also found that Calatayud taught that ciclesonide had “low systemic absorption” (id.). As to claim 13, the Examiner conceded that Calatayud did not “expressly teach ciclesonide as useful in treating inflammatory bowel diseases such as ulcerative colitis” (id.). To address that deficiency, the Examiner cited Ulmius as disclosing that a “glucocorticoid[] (budesonide) composition for oral or rectal administration (enema) can be effectively used to treat ulcerative colitis because [of] its high local anti-inflammatory effect with minimal systemic absorption” (id.). The Examiner also cited Friend as teaching “colonic delivery systems useful for deliver[ing] actives for treating ulcerative colitis to the colon. Such actives include glucocorticoids” (id.). 1 U.S. Patent No. 5,482,934 (issued January 9, 1996). 2 EP 0 502 092 B1 (published July 26, 1995). 3 U.S. Patent No. 5,811,388 (issued September 22, 1998). 4 U.S. Patent No. 5,178,866 (issued January 12, 1993). Appeal 2011-004441 Application 10/570,986 3 Based on these teachings, the Examiner concluded that an ordinary artisan would have considered it obvious to “to incorporate ciclesonide into the colonic delivery system of [Friend] for treating ulcerative colitis” (Ans. 5). The Examiner reasoned that the artisan would have been motivated to incorporate ciclesonide into Friend’s ulcerative colitis treating composition “since ciclesonide possesses excellent anti-inflammatory activity with low systemic absorption. Such characteristic is similar to that of budesonide. Therefore, employing ciclesonide in a method of treating ulcerative colitis would be reasonably expected to be similarly effective as employing budesonide” (id.). As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden . . . of presenting a prima facie case of unpatentability. . . . After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. Appellants’ arguments do not persuade us that a preponderance of the evidence fails to support the Examiner’s prima facie case of obviousness. We are also not persuaded that Appellants’ evidence of unexpected results is sufficient to outweigh the evidence of prima facie obviousness advanced by the Examiner. Appellants argue that the Examiner failed to make out a prima face case of obviousness because “there is absolutely no teaching to be found in the cited references themselves which would motivate the skilled artisan to combine the ciclesonide of the present application with the oral delivery Appeal 2011-004441 Application 10/570,986 4 system of [Friend] or the oral or rectal delivery system of the Ulmius et al. reference” (App. Br. 12). We are not persuaded. As the Examiner pointed out, Friend discloses that its oral dosage forms’ delivery of drugs to the colon is particularly valuable with respect to glucocorticoids (Friend, col. 2, l. 55, through col. 3, l. 1). Friend thus discloses a number of glucocorticoids, budesonide among the preferred ones, which can be delivered using its dosage forms in inflammatory bowel disease treatments (see id. at col. 8, ll. 13-56). Ulmius also discloses treating inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease, with “certain glucocorticosteroids” (Ulmius 3). As the Examiner pointed out, Ulmius discloses that budesonide was considered a particularly advantageous glucocorticosteroid treatment for inflammatory bowel disease because of its “high anti-inflammatory effect at the place of application but a low degree of unwanted systemic glucocorticoid side effect” (id. at 4). As the Examiner also pointed out, Calatayud discloses that the glucocorticoid compounds it discloses, which undisputedly include ciclesonide, possess precisely the attributes described by Ulmius as being desirable in its anti-inflammatory treatments (see, e.g. Calatayud, col. 1, ll. 14-17 (“The purpose of the invention is to provide … certain glucocorticoids which have a combination of high anti-inflammatory activity at the application site and a low systemic glucocorticoid activity.”)). Thus, an ordinary artisan would not only have recognized that Calatayud’s ciclesonide was the same type of compound as that described in Ulmius and Friend as being useful for treating inflammatory bowel diseases, but also that ciclesonide possessed the desirable properties of having Appeal 2011-004441 Application 10/570,986 5 relatively low systemic side effects as compared to a relatively high activity at the application site. We are therefore not persuaded that the Examiner failed to advance adequate evidence that would have prompted an ordinary artisan to treat an inflammatory bowel disorder with ciclesonide, as claim 13 requires. Rather, we find that a preponderance of the evidence supports the Examiner’s prima facie case of obviousness. As to the issue of unexpected results, as the Federal Circuit has noted, “[m]ere improvement in properties does not always suffice to show unexpected results. . . . [W]hen an applicant demonstrates substantially improved results . . . and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). In the instant case, as Appellants point out (App. Br. 13-17; see also Reply Br. 4-8), the Specification presents data purporting to show that, in the TNBS-induced rat model of inflammatory bowel disease, at all dosages tested that produced the desirable topical effect, ciclesonide had a significantly lower undesirable systemic effect as compared to budesonide, with decrease in thymus weight and increase in adrenal gland weight being the measures of the undesirable systemic side effects (see Spec. 10). The Specification explains the import of the experimental data: The results demonstrate the efficacy of ciclesonide, attenuating the TNBS-increased colon width starting with 2,3 µmol/animal. At the highest assessed dose of 6,9 µmol/animal, no additional decrease of the TNBS-reduced thymus weight could be detected. Instead, the TNBS-increased adrenal glands weight was attenuated starting with 2,3 µmol/animal ciclesonide. By contrast, budenoside [sic] seems to additionally reduce the thymus weight starting with 2,3 µmol/animal and does not Appeal 2011-004441 Application 10/570,986 6 reverse the inhibitory effect of TNBS-treatment on the adrenal glands weight in the assessed pharmacodynamic dose range. (Spec. 11.) The Examiner responds that, “when comparing the systemic effect -- thymus weight reduction, ciclesonide (compounds 8-9 in [Calatayud]) is shown to have much less systemic effect than that of budesonide because ciclesonide does not reduce the weight of thymus, whereas budesonide reduces thymus weight (See col. 17-20, Table III)” (Ans. 7). Therefore, the Examiner reasons, the low side effect profile of ciclesonide shown by Appellants “would be seen as [an] expected effect” (id.). Appellants reply that Table III of Calatayud “contains quantitative values for topical and systemic activity, along with the therapeutic index for the respective compounds. No qualitative conclusions appear in [Calatayud] to serve as a basis for this conclusion” (Reply Br. 9). We find that the Examiner has the better position here. The data in Table III of Calatayud were derived from experiments in which various compounds, undisputedly including ciclesonide, were tested to assess their desirable topical anti-inflammatory effect as compared to their undesirable systemic effect (see Calatayud, col. 15, l. 10, through col. 16, l. 3). As Calatayud explains, and as the Examiner found, the systemic effect measurement included the same thymus and adrenal gland weight changes measured by Appellants in their comparison (see id. at col. 16, ll. 5-10 (“Extraction and weighing of the thymus and adrenals were performed in all animals and a fluorometric determination of the cortisol plasma levels was Appeal 2011-004441 Application 10/570,986 7 made. We consider the variation in these parameters indicative of the systemic glucocorticoid activity of the products.”)). Moreover, like Appellants, Calatayud compared the relative topical/systemic effects of their compounds, which include ciclesonide, to budesonide, and like Appellants, found that the ciclesonide had an overall lower undesirable systemic side effect as compared to budesonide: The products that are the object of the present invention have shown in the pharmacologic studies performed a low systemic effect in relation to the topical pharmacologic activity found. The difference becomes even more evident when the reference products, budesonide, flunisolide, and triamcinolone acetonide are compared; effective local pharmacologic activity and low systemic glucocorticoid response are demonstrated. (Calatayud, col. 16, ll. 28-36.) Thus, as seen in Table III, budesonide as a reference compound is assigned an overall therapeutic index of “1” based on its relative measured topical anti-inflammatory and systemic glucocorticoid activities (see id. at cols. 19-20 (Table III)). In comparison, compounds 8 and 9, which Appellants do not dispute as being ciclesonide, had significantly higher therapeutic indices of 27.2 and 24.5 based on the same measurements (see id. at cols. 17-18 (Table III)). Therefore, while we acknowledge Appellants’ evidence that ciclesonide exhibits lower systemic side effects than budesonide, given the teachings of Calatayud discussed above, we agree with the Examiner that an ordinary artisan would not have considered those properties of ciclesonide to be unexpected. Thus, as we are not persuaded that the Examiner failed to make out a prima facie case of obviousness as to claim 13, and as we are not persuaded that Appellants have advanced adequate evidence of truly Appeal 2011-004441 Application 10/570,986 8 unexpected results, we affirm the Examiner’s rejection of claim 13 as obvious over Calatayud, Ulmius, Friend, and Wright. As they were not argued separately, the remaining claims fall with claim 13. See 37 C.F.R. § 41.37(c)(1)(vii). TIME PERIOD 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 ak