Ex Parte Filipcsei et alDownload PDFPatent Trial and Appeal BoardDec 5, 201713378640 (P.T.A.B. Dec. 5, 2017) 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. 13/378,640 02/13/2012 Genoveva Filipcsei DAN-070 (110293) 8874 12495 7590 12/05/2017 Jason D. Voight 5100A MacArthur Boulevard, NW Second Floor Washington, DC 20016 EXAMINER BROWE, DAVID ART UNIT PAPER NUMBER 1617 MAIL DATE DELIVERY MODE 12/05/2017 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 GENOVEVA FILIPCSEI, ZSOLT OTVOS, KATALIN PONGRACZ, and FERENC DARVAS1 Appeal 2017-002103 Application 13/378,640 Technology Center 1600 Before DEBORAH KATZ, ULRIKE W. JENKS, and JOHN E. SCHNEIDER, Administrative Patent Judges. KATZ, Administrative Patent Judge. DECISION ON APPEAL 1 NanoForm Hungary Ltd. is reported to be the real party-in-interest. (App. Br. 1.) Appeal 2017-002103 Application 13/378,640 Appellants seek our review, under 35 U.S.C. § 134(a), of the Examiner’s decision to reject claims 34, 36-38, and 54-57.2 (App. Br. 1.) We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. The Examiner rejected all of the claims under consideration under 35 U.S.C. § 112, second paragraph, as being indefinite. (Ans. 3-4.) The Examiner also rejected all of the claims under consideration under 35 U.S.C. § 103(a) as being obvious over Ryde3, Anderson4, and Song5. (Ans. 4-7.) Appellants do not argue for the separate patentability of any of the rejected claims. Accordingly, we focus on independent claim 34 in our review. See 37 C.F.R. § 41.37(c)(l)(iv). Appellants’ Specification is directed to formulations of sildenafil citrate, a drug known to be useful in the treatment of erectile dysfunction and marketed under the name Viagra. (Spec. 2.) Appellants’ claim 34, the only independent claim on appeal, recites: A nanostructured sildenafil composition comprising: (a) nanoparticles of sildenafil base or a pharmaceutically acceptable salt or co-crystal thereof having an average particle size of less than about 500 nm; (b) an anionic polyelectrolyte or a non-ionic stabilizer or a mixture thereof or an additional stabilizer, 2 Appellants have cancelled claims 1-33, 35, 39, 40, and 48-50 and have withdrawn claims 41-47 and 51-53 from consideration. (See Amendment filed October 26, 2015.) 3 U.S. Patent Application No. 2005/0042177 Al, published February 24, 2005. 4 U.S. Patent Application No. 2008/0199700 Al, published August 21, 2008. 5 U.S. Patent Application No. 2006/0014271 Al, published January 19, 2006. 2 Appeal 2017-002103 Application 13/378,640 wherein the composition is prepared in a microfluidic based continuous flow reactor, wherein the nano structured sildenafil composition has at least partially amorphous structure, wherein the polyelectrolyte is selected from the group consisting of nucleic acids, proteins, teichoic acids, polypeptides, polysaccharides, poly(sodium styrene sulfonate)-based polymers, poly(sodium styrene sulfonate)-based copolymers, poly(meth)acrylate-based polymers, poly(meth)acrylate-based copolymers, poly(acrylic-acid) optionally cross-linked with allyl ester, sucrose or pentaerythriol, and derivatives of poly( acrylic-acid) optionally cross-linked with allyl ester, sucrose or pentaerythriol, wherein the non-ionic stabilizer is selected from the group consisting of poly(vinyl-pyrrolidone), poly(2-ethyl-2-oxazoline), poly(methyl vinyl ether), polyvinyl alcohol, acetic acid ethenyl ester polymers with l-ethenyl-2-pyrrolidinone (PVP/V A copolymers), poly( ethylene-glycol), derivatives of poly(ethylene-glycol), ethylene oxide/propylene oxide block copolymers, derivatives of ethylene oxide/propylene oxide block copolymers, and polyoxyethylene sorbitan fatty acid esters, wherein the additional stabilizer is selected from the group consisting of hydroxyl-propylcellulose derivatives, sodium lauryl sulfate, sodium dodecyl benzene sulfonate, tocopheryl polyethylene glycol succinates, polyethoxylated castor oils, derivatives of polyethoxylated castor oils, and cationic stabilizers, wherein the composition is not a gel, and wherein the ratio of the sildenafil base or the pharmaceutically acceptable salt or co-crystal thereof to the anionic polyelectrolyte or the non-ionic stabilizer or the mixture thereof or the additional stabilizer is from 10:1 to 100:1 by weight. (App. Br. 9-10, Claims App’x.) One embodiment within claim 34 recites a nanoparticle composition with the following structural features: (a) nanoparticles of sildenafil base having an average particle size of less than about 500 nm; 3 Appeal 2017-002103 Application 13/378,640 (b) an anionic polyelectrolyte, specifically poly(acrylic-acid) optionally cross-linked with allyl ester, sucrose or pentaerythriol; wherein the nano structured sildenafil composition has at least partially amorphous structure, wherein the composition is not a gel, and wherein the ratio of the sildenafil base to the anionic polyelectrolyte is from 10:1 to 100:1 by weight. 35 U.S.C. § 112, second paragraph The Examiner rejected Appellants’ claims as being indefinite because the claimed sildenafil composition excludes gels (“wherein the composition is not a gel”), but includes an anionic polyelectrolyte as recited in (b), specifically poly(acrylic-acid) cross-linked with allyl ester, sucrose or pentaerythriol, which was known to form gels. (See Ans. 3.) The Examiner cites to Brown (U.S. Patent No. 2,798,053) as evidence of this knowledge. Appellants do not dispute that Brown teaches that poly(acrylic-acid) cross-linked with allyl ester, sucrose or pentaerythriol form a gel. Appellants, however, argue that ordinarily skilled artisans would have recognized that the polymers recited would only produce a gel under certain pH conditions and concentrations and that these conditions were well-known or readily ascertainable without undue experimentation. (App. Br. 3.) Appellants do not direct us to evidence in their Appeal Brief to support the assertion that the lack of a gel formation was well-known to the ordinary artisan. Furthermore, Appellants’ claims are not limited to specific pH or concentrations conditions. Appellants cite support for this assertion only in their Reply Brief (see Reply Br. 1-2), but this evidence is untimely. (See 37 C.F.R. § 41.41(b)(1) (“A reply brief shall not include any new or non-admitted amendment, or 4 Appeal 2017-002103 Application 13/378,640 any new or non-admitted affidavit or other Evidence.”).) Specifically, Appellants rely on “the enclosed article by Nikolopoulos found on the Internet http://www.admix.com/carbopol” to argue that the specific cross- linked polymer Carbopol would not form a gel under certain conditions. (Reply Br. 2.) Appellants also argue that this polymer is used in Example 8 of their Specification to obtain a product that is a colloidal solution, not a gel. According to Appellants, “it is within the knowledge of a skilled person to make a non-gel solution including such polymers which are otherwise capable of forming a gel under specific conditions.” (Id.) Appellants’ argument is unpersuasive, whether we consider the belatedly cited evidence or not, because it refers to only one cross-linked polymer — Carbopol. In contrast, the Examiner’s rejection is based on the knowledge in the art that poly(acrylic-acid) cross-linked with allyl ester, sucrose or pentaerythriol was known to form gels. Thus, even if it was known how to prevent one specific cross-linked polymer from forming a gel, Appellants’ claims include other polymers within the scope of the claims that were known to form gels. Appellants’ argument that “the boundaries of what is encompassed by the claim language ‘not a gel’ would be clear and precise to one possessing ordinary skill in the art in view of the specification and prior art” (App. Br. 3-4) is unpersuasive because it fails to direct us to portions of the Specification or teachings in the prior art in support. Accordingly, this argument is merely conclusory. 35 U.S.C. § 103(a) The Examiner cites Ryde for its teaching of a composition of sildenafil base and an anionic stabilizer in nanoparticles that form an 5 Appeal 2017-002103 Application 13/378,640 amorphous colloid instead of a gel. (Ans. 4-5, citing, inter alia, Ryde abstract and Tflf 91, 122, 138-39, claims 13, 14, 16.) Ryde does not expressly teach that the anionic polyelectrolyte stabilizer is a poly(acrylic acid) polymer or that the particles are prepared in a microfluidic based continuous flow reactor. The Examiner finds that one of ordinary skill in the art would have looked to the teachings of Anderson to include a poly(acrylic acid) as a stabilizer in the nanoparticles of Ryde because Anderson teaches that poly(acrylic acid) improves nanoparticle solubility, prevents nanoparticle aggregation, and allows tailoring of the drug release profile, for example to achieve sustained-release. (Anderson || 33 and 40; see Ans. 5-6.) The Examiner also finds that those of ordinary skill in the art would have considered it obvious to have used a microfluidic based continuous flow reactor as taught in Song to synthesize the nanoparticles of Ryde because Song teaches a method for manufacturing nanoparticles with a narrow size distribution that is fast, inexpensive, and highly precise. (See Ans. 5 and 11; Song, abstract and Tflf 0013-0014, 0065.) Appellants discuss the differences between the method of stabilizing drugs taught in Ryde and Appellants’ continuous flow nanoprecipitation technique. (See App. Br. 4-5.) To the extent that Appellants argue any alleged differences in the methods indicate the claims currently under consideration are patentable, we are not persuaded. Appellants claim a composition, not a method of making a composition. Thus, we are not persuaded by arguments that refer only to the differences in the methods used in the prior art. 6 Appeal 2017-002103 Application 13/378,640 For example, Appellants argue that the micro fluidic based continuous flow reactor method taught in Song relates to a different technical field and discloses the preparation of palladium nanoparticle, which, according to Appellants, is a very different type of nanoparticle. (App. Br. 6.) We are not persuaded that recitation of this process of making the nanoparticle composition product Appellants claim creates a patentable difference over the cited prior art. (See Ans. 10 (“The instant claims are directed to a ‘product-by-process.’ The determination of patentability is based on the product, and does not depend on its method of production. Indeed, if the product is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process.”).) As the Examiner found, Ryde teaches nanoparticles with the same characteristics Appellants claim: less than about 500 nm, at least partially amorphous, not a gel, as well as being soluble and redispersible. (See Ans. 10-11; see Ryde §§ 91, 122, 192, 194, 195.) “Where a product-by-process claim is rejected over a prior art product that appears to be identical, although produced by a different process, the burden is upon the applicants to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product.” In re Marosi, 710 F.2d 799, 803 (Fed. Cir. 1983). Appellants fail to direct us to evidence that the nanoparticles of Ryde modified as taught in Anderson would be different from those prepared in a microfluidic based continuous flow reactor. Appellants argue that the technique taught in Ryde produces a product with solubility that differs from the solubility of the claimed composition. (App. Br. 5.) Appellants also argue that Anderson teaches nanoparticles of 7 Appeal 2017-002103 Application 13/378,640 metals and metal alloys, not sildenafil and does not suggest using a stabilizer polymer with sildenafil to increase its solubility. (Id.) Appellants argue further that Song does not teach anything about the preparation of nanoparticles of organic compounds. (App. Br. 6.) Each of these arguments addresses the prior art references individually. The rejection is based on the obviousness of modifying the nanoparticles taught in Ryde according to the teachings of Anderson and Song. “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references.” In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellants argue further that Anderson relates to CdTe-CdS photoluminescent quantum dots and that the nanoparticles it teaches have a metal core, which would not be useful for pharmaceutically active compounds. (App. Br. 5.) Again, Appellants do not address the Examiner’s rejection. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, 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 (C.C.P.A. 1981). According to Appellants, the metallic core of the particles taught in Anderson are essential and only hindsight based on Appellants’ Specification indicates that one of ordinary skill in the art would attempt to 8 Appeal 2017-002103 Application 13/378,640 use the stabilizer of Anderson with the nanoparticles of Ryde, which lack a metallic core. (App. Br. 5-6.) We are not persuaded by this argument because Anderson teaches that “[a] wide variety of molecules can be used to form the nanoparticle” surrounded by the stabilizer layer of the invention, including nanoparticles of organic or inorganic charged ions or combinations thereof. (See Anderson 136.) Because Anderson is not limited to nanoparticles with a metallic core, we are not persuaded by Appellant’s argument that it is essential to the use of a poly(acrylic acid) polymer as taught in Anderson. Appellants also argue that the claimed nano structured sildenafil compositions demonstrate unexpected results that indicate they are patentable over the prior art. (App. Br. 7.) Appellants argue that “the very high increase in solubility supported by example 2 of the present application [6.8-times (i.e. 680 %) increase in solubility!] should be regarded as an unexpected, ‘non-obvious’ result” because none of the references cited by the Examiner report a similar increase in solubility. (App.Br. 7.) Appellants argue further that other “excellent physical properties,” including enhanced redispersibility and wettability, enhanced lipophilicity through the cell membranes, and preferred serum concentration profile both in fasted and fed state. (App. Br. 7.) We are not persuaded by these arguments because Appellants do not direct us to evidence that one of ordinary skill in the art would have found any of these characteristics to be unexpected over the combination of the teachings of the cited prior art. Although Examples 2, 5, and 6 of Appellants’ Specification reports solubility of nano structured sildenafil citrate to be 6.8 times higher than the solubility of sildenafil citrate in 9 Appeal 2017-002103 Application 13/378,640 distilled water (see Spec. 10:9-10), increased redispersibility (see id. 11:30-12:10), and enhanced wettability (see id. 13:10-20), the Specification does not indicate that these results were unexpected and Appellants do not direct us to other evidence, such as the testimony of one of skill in the art. Furthermore, as the Examiner explained, Example 2 of Appellants’ Specification compares nanostructured sildenafil with stabilizer to sildenafil citrate that is not in particulate form and is not formulated with a stabilizer. (See Ans. 13.) Ryde teaches that nanostructured sildenafil base exhibits increased bioavailability, improved pharmacokinetic profiles, and advantages over non-nanoparticulate sildenafil compositions or nanoparticulate sildenafil citrate compositions. (See Ryde Tflf 57 and 67.) Appellants’ evidence does not provide a comparison between the claimed composition and that of the prior art, for example the composition of Ryde. Accordingly, we are not persuaded that Appellants’ claimed invention demonstrates results that would not have been expected by those of ordinary skill in the art. 10 Appeal 2017-002103 Application 13/378,640 CONCLUSION Upon consideration of the record and for the reasons given, the rejection of claims 34, 36-38, and 54-57 under 35 U.S.C. § 103(a) over 35 U.S.C. § 112, second paragraph, is sustained. The rejection of the same claims under 35 U.S.C. 35 U.S.C. § 103(a) is also sustained. Therefore, we affirm the decision of the Examiner. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136. AFFIRMED 11 Copy with citationCopy as parenthetical citation