Ex Parte GeczyDownload PDFBoard of Patent Appeals and InterferencesFeb 16, 201010182718 (B.P.A.I. Feb. 16, 2010) 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. 10/182,718 10/02/2002 Jozsef-Michel Geczy 02138 7742 23338 7590 02/16/2010 DENNISON, SCHULTZ & MACDONALD 1727 KING STREET SUITE 105 ALEXANDRIA, VA 22314 EXAMINER EBRAHIM, NABILA G ART UNIT PAPER NUMBER 1618 MAIL DATE DELIVERY MODE 02/16/2010 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 BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte JOZSEF-MICHEL GECZY __________ Appeal 2009-008542 Application 10/182,718 Technology Center 1600 __________ Decided: February 16, 2010 __________ Before MELANIE L. MCCOLLUM, JEFFREY N. FREDMAN, and STEPHEN WALSH, Administrative Patent Judges. WALSH, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a sustained-release oral form of molsidomine. The Patent Examiner rejected the claims on the ground of obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. Appeal 2009-008542 Application 10/182,718 2 STATEMENT OF THE CASE The drug molsidomine is said to be “particularly useful for the preventive treatment of all forms of angina attack insofar as its action causes a relaxation of the vascular smooth muscle fiber . . . .” (Spec. 1:8-10.) According to the Specification, the claimed form of molsidomine has advantages over the forms on the market because a single daily dose improves patient comfort and compliance, and “maintenance of a high maximum plasma concentration guarantees an optimum efficacy.” (Id. at 3:17-25.) Claims 24-40, which are all the pending claims, are on appeal. Claim 24 is representative and reads as follows: 24. A sustained-release solid oral galenical form of molsidomine which contains a sustained-release matrix containing a therapeutically effective amount of molsidomine or one active metabolite of molsidomine selected from the group consisting of SIN-1 and SIN-lA, said matrix consisting essentially of: -at least 40% by weight of a material selected from the group consisting of: a polymeric material having a high swelling capacity in contact with water or aqueous liquids and gelling properties, and which is a high molecular weight hydroxypropyl methyl cellulose; and a mixture of a polymeric material having a high swelling capacity in contact with water or aqueous liquids selected from the group consisting of crosslinked sodium carboxymethylcellulose, a crosslinked hydroxypropylcellulose, a high molecular weight hydroxymethylpropylcellulose, a polymethylmethacrylate, a crosslinked polyvinylpyrrolidone and a high molecular weight polyvinylalcohol, and a gellable polymeric material selected from the group consisting of methylcellulose, carboxymethylcellulose, a low molecular weight hydroxypropylmethylcellulose, a low molecular weight polyvinylalcohol, a polyethyleneglycol and a non-crosslinked polyvinylpyrrolidone; Appeal 2009-008542 Application 10/182,718 3 -between 12% and 25% by weight of a lipophilic substance selected from the group consisting of glycerol behenate, an hydrogenated castor oil, glyceryl palmitostearate and glyceryl monooleate; and -at least 25% by weight of at least one adjuvant selected from the group consisting of diluents, lubricants, granulating agents, flow improvers and colorants; said galenic form having an in vitro dissolution rate, measured spectrophotometrically at 286 or 311 nm by the method described in the European Pharmacopoeia, 3rd edition or by the method USP XXIV, at 50 rpm, in 500 ml of a 0.1 N HCl medium, at 37°C of: - 15 to 25% of molsidomine released after 1 hour - 20 to 35% of molsidomine released after 2 hours - 50 to 65% of molsidomine released after 6 hours - 75 to 95% of molsidomine released after 12 hours - >85% of molsidomine released after 18 hours - >90% of molsidomine released after 24 hours, and providing a plasma concentration of at least 5 ng/ml of plasma, over a period of about 24 hours, the plasma peak of molsidomine obtained in vivo occurring 2.5 to 5 hours following the administration of said form, and having a value of between 25 and 40 ng/ml of plasma. The Examiner rejected claims 24-40 under 35 U.S.C. § 103(a) as unpatentable over the combined teachings of Wunderlich,1 Wong,2 and Saslawski.3 Claims 25-40 have not been argued separately and therefore stand or fall with claim 24. 37 C.F.R. § 41.37(c)(1)(vii). 1 US 6,068,854, issued to Jens-Christian Wunderlich et al., May 30, 2000. 2 US 5,962,013, issued to Ooi Wong et al., Oct. 5, 1999. 3 US 6,426,087 B1, issued to Olivier Saslawski et al., Jul. 30, 2002. Appeal 2009-008542 Application 10/182,718 4 OBVIOUSNESS The Issue The Examiner’s position is that Wunderlich taught a matrix medicament used for controlled release of drugs, and taught molsidomine as one of the drugs whose release could be controlled. (Ans. 3.) According to the Examiner, Wunderlich taught the same matrix materials recited in Appellant’s claims, but did not teach the dose recited in the claims. (Id.) The Examiner found “it is within the skills of a person of ordinary skill in the art to provide the perfect dose to each patient according to the severity of the disease. It is also within the ability of the artisan to adjust the amounts of polymers included in the claims since its properties are known to achieve the sustained-release needed.” (Id. at 3-4.) The Examiner found that Wong suggested adding the optionally claimed metabolite SIN-1. (Id.) The Examiner found that Saslawski disclosed ingredients that “control the kinetics of release of the active ingredient,” including glycerol behenate in an amount of 20%, and taught how to control drug release by incorporating glycerol palmitostearate, a hydrogenated castor oil, glycerol behenate, or stearic acid. (Id. at 4-5.) Based on these findings, the Examiner concluded that it would have been obvious “to achieve a galenic prolonged release allowing improved absorption by the gastrointestinal tract of active ingredients and also to control the kinetics of release of the active ingredient.” (Id. at 5, citations omitted.) Appellant contends that “none of the cited references discloses or suggests the claimed release profile, in itself, or in combination with molsidomine.” (App. Br. 9.) According to Appellant, Wunderlich gave “no Appeal 2009-008542 Application 10/182,718 5 reason . . . to provide molsidomine in a 24 hour dosage having the claimed release profile,” and Wunderlich’s examples result in 95-100% release after 6 hours. (Id.) Appellant contends that (1) nothing in Wong would lead to a 24 hour molsidomine dosage (id.), (2) Saslawski’s release profile “is not known, the graphs of Figs. 1-9 being limited to 8 hours” (id.), and (3) it is not known how Saslawski’s “release profile would apply to molsidomine, which is not discussed in Saslawski” (id. at 10). According to Appellant, the Inventor’s Declaration under Rule 132 shows the claimed composition provides safe, therapeutic levels of molsidomine over a period of up to 24 hours, in contrast to conventional formulations. (Id. at 10-12.) Further, Appellant argues, the claimed formulation when administered as a once a day 16 mg formulation “totally unexpectedly” reduced angina attacks in comparison to a known 8 mg sustained release formulation administered twice a day. (Id. at 6.) The issue with respect to this appeal is whether Appellant rebutted the Examiner’s conclusion of obviousness. Findings of Fact 1. Wunderlich described an oral medicament composed of a gelatin matrix, in which the release of the medicament “is variable in time and may be adjusted according to the medicament.” (Wunderlich, Abstract.) 2. Wunderlich taught that suitable pharmaceuticals for sustained release included molsidomine. (Id. at 6:35-36.) 3. Wunderlich disclosed gelatin tablets having dissolution times from 55 to 627 minutes. (Id. at 10:20-66.) Appeal 2009-008542 Application 10/182,718 6 4. Wunderlich provided examples in which 100% of a drug were released in 7 hours (Example 3) and 6 hours (Example 4), respectively. (Id. at 11:35 – 12:32.) 5. Wong described a monolithic matrix formulation for transdermal administration of molsidomine. (Wong, Abstract.) 6. Wong disclosed that molsidomine “can be metabolized to SIN-1, which is readily converted into the active metabolite SIN-1A.” (Id. at 3:62-64.) 7. Saslawski described “orally administrable galenic forms comprising one or more active ingredients.” (Saslawski, 1:11-12.) 8. Saslawski’s dosage forms “allow[] increased control of the rate of release during the phase of prolonged release of the active ingredient.” (Id. at 2:11-15.) 9. In Example 20, Saslawski reported that: The matrix tablet form…and the semisolid gelatin capsule form make it possible to maintain or even increase the relative bioavailability of acamprosate, and furthermore the levels observed … at 6 h and 24 h are greater than those observed for the reference gelatin capsule. (Id. at 24:20-27.) 10. According to Appellants’ Specification: a preliminary clinical study has shown, totally unexpectedly, that patients whose condition is stabilized by a twice daily treatment with molsidomine (sustained- release tablets containing an 8 mg dose), accompanied by the sublingual administration of organic nitro derivatives during attacks, exhibit a significant reduction in angina attacks, and consequently in the consumption of organic Appeal 2009-008542 Application 10/182,718 7 nitro derivatives, after treatment with a galenical form according to the invention (containing e.g. a 16 mg dose). (Spec. 3:31-4:2.) Principles of Law When determining whether a claim is obvious, an Examiner must make “a searching comparison of the claimed invention – including all its limitations – with the teaching of the prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995). “Rejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006), cited with approval in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007). [E]ven though applicant’s modification results in great improvement and utility over the prior art, it may still not be patentable if the modification was within the capabilities of one skilled in the art, unless the claimed ranges “produce a new and unexpected result which is different in kind and not merely degree from the results of the prior art.” In re Huang, 100 F.3d 135, 139 (Fed. Cir. 1996) (citations omitted). Analysis The Examiner found that “the combination of Wunderlich, Wong, and Saslawski should provide the said release profile since [the] same composition should have the same properties and functions.” (Ans. 7.) The problem with this argument is that claim 24 lists specific weight percentages Appeal 2009-008542 Application 10/182,718 8 of several components, but the cited prior art provided little if any guidance toward those specific percentages in combination. Even if we were to agree that adjustment of the prior art parameters to achieve the 24 hour drug release taught by Saslawski, for any of the drugs Wunderlich listed, was within the skill in the art, and would have resulted in a composition having the components in the proportions of claim 24, that would not resolve the question of obviousness in this case. Appellant argues that the claimed dosage form had a “totally unexpected[]” result. (App. Br. 6.) That is, even patients already being treated with twice daily 8 mg sustained release molsidomine experienced a significant reduction in angina attacks when given a single 16 mg sustained release molsidomine of Appellant’s composition. We accept the disclosure as a fact. (FF10.) The Examiner did not address this result that the Specification reported. Instead, the Examiner found that “[t]he expected result [of combining the prior art teachings] would be a galenic prolonged release tablet . . . .” (See, e.g., Ans. 8.) While we agree that the expected result of combining the prior art teachings would have been a prolonged release tablet, the Examiner did not argue or provide evidence that patients given Appellant’s formulation would have been expected to exhibit a “significant reduction” in angina attacks over the same quantity of drug administered in a different sustained release formulation. Based on the uncontested Specification report, we conclude that Appellant has met the Huang standard. See Huang, 100 F.3d at 139. CONCLUSIONS OF LAW Appellant rebutted the conclusion of obviousness. Appeal 2009-008542 Application 10/182,718 9 SUMMARY We reverse the rejection of claims 24-40 under 35 U.S.C. § 103(a) as unpatentable over the combined teachings of Wunderlich, Wong, and Saslawski. REVERSED lp DENNISON, SCHULTZ & MACDONALD 1727 KING STREET SUITE 105 ALEXANDRIA VA 22314 Copy with citationCopy as parenthetical citation