Ex Parte Weigandt et alDownload PDFPatent Trials and Appeals BoardJun 20, 201914380989 - (D) (P.T.A.B. Jun. 20, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 14/380,989 08/26/2014 23599 7590 06/24/2019 MILLEN, WHITE, ZELANO & BRANIGAN, P.C. 2200 CLARENDON BL VD. SUITE 1400 ARLINGTON, VA 22201 Markus Weigandt 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. MERCK-4222 5630 EXAMINER GOTFREDSON,GAREN ART UNIT PAPER NUMBER 1619 NOTIFICATION DATE DELIVERY MODE 06/24/2019 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): docketing@mwzb.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte MARKUS WEIGANDT, SENTA VOSS, TOBIAS MILLER, and ACHIM GOEPFERICH Appeal 2018-004330 Application 14/380,989 1 Technology Center 1600 Before RYAN H. FLAX, RACHEL H. TOWNSEND, and CYNTHIA M. HARDMAN, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a process for the production of nanoparticles, which have been rejected as indefinite and/or as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. STATEMENT OF THE CASE Appellant's Specification explains that "[n]anoparticles based on polymers can be produced using various processes" such as solvent evaporation, co-solvent evaporation, dialysis and film hydration. (Spec. 2- 1 Appellant is Merck Patent GmbH, which is a wholly owned subsidiary of Merck KGaA. (Appeal Br. 1.) Appellant identifies itself as the real party in interest. (Id.) Appeal 2018-004330 Application 14/380,989 4). According to Appellant's Specification "[p]roduction ofnanoparticles with proven polymers by means of the[ se] processes ... often results in active-compound loading which is inadequate for therapeutic use thereof." (Id. at 4.) Appellant's Specification also states that "known processes also result in nanoparticles from which the active compound is only released with a certain time delay (lag time)." (Id.) Appellant's invention is directed to a process of making an active compound laden nanoparticle that avoids the disadvantages of the prior art. (Id. at 1, 5.) Claims 1-20 are on appeal. Claim 1 is representative and reads as follows: 1. Process for the production of nanoparticles comprising the steps of (a) dissolution of at least one active compound and at least one polymer in an organic solvent, (b) mixing of the solution prepared in step (a) with an aqueous phase, ( c) evaporation of the organic solvent, ( d) purification of the nanoparticles laden with active compound obtained in step ( c) by means of dialysis against aqueous dialysis solution comprising the same active compound. (Supplemental Appeal Br. 3. )2 2 The Supplemental Appeal Brief was filed September 21, 201 7 in response to a Notice of Non-Compliant Appeal Brief. 2 Appeal 2018-004330 Application 14/380,989 The following grounds of rejection by the Examiner are before us on review: Claims 6 and 20 under 35 U.S.C. § 112, second paragraph, as indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention. Claims 1, 4-13, 15-17, and 20 under 35 U.S.C. § 103 as unpatentable over Letchford3 and Washington. 4 Claims 2, 3, 18, and 19 under 35 U.S.C. § 103 as unpatentable over Letchford, Washington, and Elkharraz. 5 Claim 14 under 35 U.S.C. § 103 as unpatentable over Letchford, Washington, and Koltenzburg. 6 DISCUSSION Indefiniteness In claim 6, the Examiner finds the language "additionally polyacrylic acid and derivatives thereof, or polysiloxane and derivatives thereof' renders the claim ambiguous as to whether the "polyacrylic acid and derivatives thereof, or polysiloxane and derivatives thereof' are part of the group of 3 Letchford et al., A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes, 65 Eur. J. Pharmaceutics and Biopharmaceutics 259-69 (2007). 4 C. Washington, Evaluation of non-sink dialysis methods for the measurement of drug release from colloids: effects of drug partition, 56 Int'l J. of Pharmaceutics 71-74 (1989). 5 Elkharraz et al., Paclitaxel-loaded microparticles and implants for the treatment of brain cancer: Preparation and physicochemical characterization, 314 Int'l J of Pharmaceutics 127-136 (2006). 6 Koltenzburg et al., US2007/0122436 Al, published May 31, 2007. 3 Appeal 2018-004330 Application 14/380,989 recited hydrophobic components of the block copolymer or whether they are additional to the hydrophobic components. (Final Action 2-3.) Similarly, in claim 20, the Examiner finds the language "furthermore hydroxypropylethylacrylic acid, or hydroxypropylmethylacrylic acid, polysiloxane and derivatives thereof' renders the claim ambiguous as to whether the "hydroxypropylethylacrylic acid, or hydroxypropylmethylacrylic acid, polysiloxane and derivatives thereof' are part of the group of recited hydrophobic components of the block copolymer or whether they are additional to the hydrophobic components. (Id.) Appellant argues that the Supreme Court held that a claim is invalid for indefiniteness "'if its claims, read in light of the specification delineating the patent, and the prosecution history, fail to inform, with reasonable certainty those skilled in the art about the scope of the invention."' (Reply Br. 2 quoting Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2129 (2014).) Appellant contends "that 'one skilled in the art would interpret the language in claims 6 and 20 as defining the polyacrylic acid or polysiloxane polymers as present in addition to the recited hydrophobic components"' and thus the claims are not ambiguous when read in light of the prosecution history. (Reply Br. 2 (quoting Appeal Br. 10.)) In determining whether a claim is definite under 35 U.S.C. § 112, second paragraph, "[t]he USPTO, in examining an application, is obliged to test the claims for reasonable precision." In re Packard, 751 F.3d 1307, 1313 (Fed. Cir. 2014); see also Ex parte McAward, Appeal 2015-006416, 2017 WL 3669566, at *5-6 (PTAB Aug. 25, 2017) (precedential). The Office "determines the scope of claims ... upon giving claims their broadest reasonable construction 'in light of the specification as it would be 4 Appeal 2018-004330 Application 14/380,989 interpreted by one of ordinary skill in the art."' Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (en bane) (quoting In re Am. Acad. of Sci. Tech Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004)). While Appellant provides attorney argument as to the meaning one of ordinary skill in the art would ascribe to claims 6 and 20, "[a]ttorney's argument in a brief cannot take the place of evidence." In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). We agree with the Examiner's position that claims 6 and 20 are subject to alternative interpretations making it unclear whether the "polyacrylic acid and derivatives thereof, or polysiloxane and derivatives thereof' or the "hydroxypropylethylacrylic acid, or hydroxypropylmethylacrylic acid, polysiloxane and derivatives thereof' are part of the group of recited hydrophobic components of the block copolymer or whether they are additional to the hydrophobic components. In light of the foregoing lack of clarity, we agree with the Examiner that there is a reasonable lack of precision as to the metes and bounds of the claim. Thus, we agree with the Examiner's conclusion that claims 6 and 20 are indefinite. II Non-Obviousness The Examiner finds that Letchford teaches two processes for production of nanoparticles that involve steps a and b as claimed. (Final Action 4.) The Examiner explains further both processes involve removal of solvent, but that one of the processes employs dialysis to remove the solvent after the nanoparticles are formed, and the other removes solvent by evaporation. (Id.) The Examiner contends that it would have been prima facie obvious to use both the dialysis and evaporation steps in a single process "to better remove the solvent, since ... it is prima facie obvious to 5 Appeal 2018-004330 Application 14/380,989 combine two process steps when both of them are taught by the prior art as useful for achieving the same result (See In re Kerkhoven, 626 F.2d 846, 850 ... (CCPA 1980) .... " (Id. at 6-7.) The Examiner recognizes that in Appellant's claims, "the dialysis step is conducted against an aqueous dialysis solution that comprises the same active component that is loaded onto the nanoparticles." (Id. at 5.) The Examiner contends that including such an active component in the aqueous dialysis solution would have been obvious in light of the teachings of Washington. (Id. at 6-7.) According to the Examiner, Washington discloses that when a drug is loaded onto a colloidal nanoparticle carrier, the drug concentration that drives diffusion across the diffusion membrane is reduced compared to a system that involves drug with no carrier. (Id. at 6.) The Examiner contends that the reduction in concentration is "by a factor of the drug/carrier partition coefficient since some of the drug remains loaded on the nanoparticle." (Id.) The Examiner contends that "Washington makes it clear that in a solution comprising a drug-loaded nanoparticle there will be an equilibrium between free drug and drug loaded on the nanoparticle, and that the concentration of free drug in a solution being used in a dialysis process will affect the diffusion rate." (Id.) According to the Examiner, therefore, it would have been obvious to one of ordinary skill in the art to include an active in the dialysis solution to "help prevent loss of the active from the nanoparticle carrier product during the dialysis caused by partitioning of the drug between the nanoparticle carrier product during dialysis caused by partitioning of the drug between the nanoparticles and the surrounding solution." (Id. at 7.) 6 Appeal 2018-004330 Application 14/380,989 We disagree with the Examiner that it would have been obvious from the disclosure of Letchford to combine an evaporation solvent removal step with a dialysis solvent removal step as asserted by the Examiner. We do not reach the issue of the obviousness as to the addition of the active in the dialysis solution. The Examiner's reliance on Kerkhoven in asserting that the combination of an evaporation step and a dialysis step in solvent removal would have been prima facie obvious (Final Action 7) is misplaced. In that case, claims directed to a mixture of spray-dried anionic and spray-dried nonionic surfactants were held to be prima facie obvious in view of prior art describing the use of each of the surfactants in a spray-dried form. Kerkhoven, 626 F .2d at 850 ("In the case at bar, [the] appealed claims ... require no more than the mixing together of two conventional spray-dried detergents. Thus, these claims set forth prima facie obvious subject matter."). In other words, the case stands for the proposition that "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose." Id. The issue here is, instead, whether it would have been obvious to combine two different solvent evaporation steps in a single process for forming drug loaded nanoparticles. While we do not agree that Kerkhoven governs the outcome here, we consider "what the combined teachings of th[ e prior art] references would have suggested to those of ordinary skill in the art." In re Keller, 642 F.2d 413,425 (CCPA 1981). We conclude that it would not have been obvious to combine dialysis solvent removal as taught by Letchford after the evaporation solvent removal in the method of making 7 Appeal 2018-004330 Application 14/380,989 a drug loaded nanoparticle as taught by Letchford for the reasons explained by Appellant. (Reply Br. 5; Appeal Br. 5.) According to the Examiner, the use of the two different solvent removal methods would have been obvious because it would result in a process of better solvent removal. (Final Action 6.) Moreover, the Examiner asserts that evaporation of a solvent can involve "either a water miscible organic solvent or a water immiscible organic solvent." (Ans. 7-8). However, as Appellant notes (Reply Br. 5), Letchford teaches that in processes of making a drug loaded nanoparticle where the "copolymer is not readily soluble in water," the dialysis method is used when the copolymer and drug are solubilized in a water-miscible organic solvent to form the nanoparticles, whereas solvent evaporation is used in conjunction with an oil-in-water emulsion procedure to form the nanoparticles, which involves the addition of a solution of the copolymer with the drug and a volatile, non- water miscible organic solvent. (Letchford 262-63.) In each procedure for forming the nanoparticles where the copolymer is not readily soluble in water, a different type of organic solvent is used in the formation of the nanoparticles, and thus a different solvent is required to be removed. Consequently, we agree with Appellant (Reply Br. 5) that there would be no reason to add the dialysis solvent removal step used to remove a water- miscible solvent to Letchford's oil-in-water emulsion process that employs solvent evaporation of a volatile, non-water miscible organic solvent to form the drug loaded nanoparticles. For the foregoing reasons, we do not sustain the Examiner's rejection of claims 1, 4-13, 15-17, and 20 as being obvious. 8 Appeal 2018-004330 Application 14/380,989 In the remaining obviousness rejections, the Examiner relies on the additional references to address dependent claim limitations, not the obviousness of combining a dialysis step with the evaporation step. (See Final Action 10.) Thus, for the reasons just discussed we also do not sustain the Examiner's rejections of claims 2, 3, 14, 18, and 19. SUMMARY We affirm the rejection of claims 6 and 20 under 35 U.S.C. § 112, second paragraph, as being indefinite. We reverse the rejection of claims 1, 4-13, 15-1 7, and 2 0 under 3 5 U.S.C. § 103 as unpatentable over Letchford and Washington. We reverse the rejection of claims 2, 3, 18, and 19 under 35 U.S.C. § 103 as unpatentable over Letchford, Washington, and Elkharraz. We reverse the rejection of claim 14 under 35 U.S.C. § 103 as unpatentable over Letchford, Washington, and Koltenzburg. 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. § l .136(a). AFFIRMED-IN-PART 9 Copy with citationCopy as parenthetical citation