Ex Parte Ryde et al

Patent Trial and Appeal BoardOct 9, 2012

11979253 (P.T.A.B. Oct. 9, 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. 11/979,253 10/31/2007 Tuula Ryde 029318-1618 6324 31049 7590 10/10/2012 Elan Drug Delivery, Inc. c/o Foley & Lardner 3000 K Street, N.W. Suite 500 Washington, DC 20007-5109 EXAMINER AHMED, HASAN SYED ART UNIT PAPER NUMBER 1615 MAIL DATE DELIVERY MODE 10/10/2012 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 TUULA RYDE, NIELS RYDE, H. WILLIAM BOSCH, JOHN D. PRUITT, and CHRISTIAN F. WERTZ __________ Appeal 2011-012628 Application 11/979,253 Technology Center 1600 __________ Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and STEPHEN WALSH, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a sterile low viscosity liquid dosage form. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Appeal 2011-012628 Application 11/979,253 2 Statement of the Case Background “The present invention is directed to low viscosity liquid dosage forms, capable of high dose loading, comprising nanoparticulate active agents.” (Spec. 9 ¶ 0022.) The Claims Claims 1, 2, 6-9, 11-14, and 16-19 are on appeal. Claim 1 is representative 1 and reads as follows: 1. A sterile, low viscosity liquid dosage form comprising: (a) particles of at least one active agent; (b) at least one surface stabilizer; and (c) at least one pharmaceutically acceptable excipient, carrier, or a combination thereof, wherein: (i) the active agent particles have an effective average particle size of less than about 200 nm, (ii) the dosage form has a viscosity of less than about 2000 mPa·s at a shear rate of 0.1 (l/s), and (iii) the dosage form is sterilized by passing through a filter having a pore size of about 0.2 microns. The issues 2 A. The Examiner rejected claims 1, 2, 6-9, 11-14, and 16-19 under 35 U.S.C. § 103(a) as obvious over Liversidge, 3 Ryde, 4 and Violante 5 (Ans. 4- 9). 1 See Appeal Br. 6 (“Independent claim 1 is to be argued in the brief.”) 2 The double patenting rejections over US applications 10/619,539 and 10/697,716 are moot in view of the abandonment of those applications. Appeal 2011-012628 Application 11/979,253 3 B. The Examiner rejected claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 3, 12, and 18 of US Application 10/420,927 and Bosch 6 (Ans. 9-10). C. The Examiner rejected claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 113- 119 and 122-151 of US Application 10/878,623 (Ans. 10). D. The Examiner rejected claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 113- 131 of US Application 11/093,149 (Ans. 10-11). E. The Examiner rejected claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 1-24 and 36-39 of US Application 10/701,064 and Bosch (Ans. 11). F. The Examiner rejected claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 1-3, 5-8, 9-14, 17-22, 28-41, and 43-47 of US Application 10/697,716 (Ans. 12). A. 35 U.S.C. § 103(a) over Liversidge, Ryde, and Violante The Examiner finds that “Liversidge discloses a pharmaceutical composition comprising particles consisting essentially of an NSAID (reading on claims 1 and 14) having a surface modifier (reading on claim 1) adsorbed on the surface thereof in an amount sufficient to maintain an average particle size of less than about 300 nm” (Ans. 5). The Examiner finds that Liversidge teaches that the “composition may further comprise 3 Liversidge et al., US 5,552,160, issued Sep. 3, 1996. 4 Ryde et al., US 6,375,986 B1, issued Apr. 23, 2002. 5 Violante et al., US 4,783,484, issued Nov. 8, 1988. 6 Bosch et al., US 6,428,814 B1, issued Aug. 6, 2002. Appeal 2011-012628 Application 11/979,253 4 excipients (see col. 3, line 34) and carriers” (id.). The Examiner finds that “Liversidge discloses a composition premix viscosity of as low as 1 centipoise (mPa·s) . . . Furthermore, Liversidge discloses an average particle size which overlaps with that of the instant application (see above) and discloses the same dispersion media” (Ans. 5-6). The Examiner finds that “use of sterile liquid dosage forms was known in the art at the time the instant application was filed, as evinced by Violante” (id. at 6). The Examiner finds that “Ryde teaches solid dose nanoparticulate compositions having at least one polymeric surface stabilizer (see col. 5, lines 20-24). The effective average particle size is disclosed as, inter alia, less than about 200 nm” (id. at 7). The Examiner finds that the ordinary artisan “would have been motivated to make such a composition because it leads to dramatically superior redispersion of the nanoparticulate composition upon reconstitution of a dry powder prepared from a nanoparticulate composition in an aqueous electrolyte solution, as explained by Ryde” (id. at 8-9). The issue with respect to this rejection is: Does the evidence of record support the Examiner‟s conclusion that Liversidge, Ryde and Violante render the composition of claim 1 obvious? Findings of Fact 1. The Specification teaches that the “active agent can be selected from a variety of known classes of drugs, including, for example . . . NSAIDS” (Spec. 20 ¶ 0055). 2. Liversidge teaches “that surface modified nanoparticles comprising an NSAID, e.g., naproxen, demonstrate reduced gastric irritation Appeal 2011-012628 Application 11/979,253 5 and/or a more rapid onset of action following oral administration” (Liversidge, col. 2, ll. 35-38). 3. The Specification teaches that “[u]seful surface stabilizers which can be employed in the invention include, but are not limited to, known organic and inorganic pharmaceutical excipients” (Spec. 21 ¶ 0058). 4. The Specification teaches that “[r]epresentative examples of surface stabilizers include . . . polyvinylpyrrolidone” (Spec. 22 ¶ 0059). 5. Liversidge teaches that “[s]uitable surface modifiers can preferably be selected from known organic and inorganic pharmaceutical excipients. Such excipients include . . . polyvinylpyrrolidone” (Liversidge, col. 3, ll. 29-49). 6. The Specification teaches that “[p]harmaceutical compositions according to the invention may also comprise one or more binding agents, filling agents, lubricating agents, suspending agents, sweeteners, flavoring agents, preservatives, buffers, wetting agents, disintegrants, effervescent agents, and other excipients. Such excipients are known in the art” (Spec. 27 ¶ 0066). 7. Liversidge teaches that “[t]wo or more surface modifiers can be used in combination” (Liversidge, col. 3, ll. 55-56). 8. Liversidge teaches that “[p]harmaceutical compositions according to this invention include the particles described above and a pharmaceutically acceptable carrier therefor. Suitable pharmaceutically acceptable carriers are well known to those skilled in the art” (Liversidge, col. 6, ll. 62-65). Appeal 2011-012628 Application 11/979,253 6 9. The Specification teaches that the “dispersion media can be, for example, water, safflower oil, ethanol, t-butanol, glycerin, polyethylene glycol (PEG), hexane, or glycol. A preferred dispersion media is water” (Spec. 32 ¶ 0086). 10. Liversidge teaches that the “preferred liquid dispersion medium is water. However, the invention can be practiced with other liquid media in which the NSAID is poorly soluble and dispersible including, for example, aqueous salt solutions, safflower oil and solvents such as ethanol, t-butanol, hexane and glycol” (Liversidge, col. 2, ll. 58-63). 11. Liversidge teaches that the “apparent viscosity of the premix suspension is preferably less than about 1000 centipoise” (Liversidge, col. 4, ll. 64-65). 12. The Examiner finds that regarding viscosity “Liversidge discloses a composition premix viscosity of as low as 1 centipoise . . . Liversidge discloses an average particle size which . . . overlaps with that of the instant application (see above) and discloses the same dispersion media . . . . As, claimed, applicants‟ composition contains the same components in the same configuration as the prior art” (Ans. 5-6). 13. The Specification teaches that: The liquid dosage forms of the invention comprise nanoparticulate active agents having an effective average particle size of less than about 2 microns (i.e., 2000 nm). In other embodiments of the invention, the active agent can have an effective average particle size of less than about 1900 nm, less than about 1800 nm, less than about 1700 nm, less than about 1600 nm, less than about 1500 nm, less than about 1400 nm, less than about 1300 nm, less than about 1200 nm, less than about 1100 nm, less than about 1000 nm, Appeal 2011-012628 Application 11/979,253 7 less than about 900 nm, less than about 800 nm, less than about 700 nm, less than about 600 nm, less than about 500 nm, less than about 400 nm, less than about 300 nm, less than about 250 nm, less than about 200 nm, less than about 150 nm, less than about 100 nm, less than about 75 nm, or less than about 50 nm (Spec. 28-29 ¶ 0073). 14. Liversidge teaches that in “preferred embodiments of the invention, the effective average particle size is less than about 300 nm” (Liversidge, col. 4, ll. 28-30). 15. Liversidge teaches a formulation of indomethacin where the “average particle size was 216 nm” (Liversidge, col. 10, ll. 25-26). 16. Ryde teaches that solid dose nanoparticulate compositions having at least one polymeric surface stabilizer and DOSS exhibit dramatically superior redispersion of the nanoparticulate composition upon administration to a mammal, such as a human or animal, or upon reconstitution of a dry powder prepared from a nanoparticulate composition in an aqueous electrolyte solution. (Ryde, col. 5, ll. 17-23.) 17. Ryde teaches that the “nanoparticulate active agent compositions, comprising a nanoparticulate active agent and at least one polymeric surfactant, have an effective average particle size prior to incorporation in a solid dose form of . . . less than about 200 nm” (Ryde, col. 6, ll. 27-33). Appeal 2011-012628 Application 11/979,253 8 18. Ryde teaches “[m]illing of aqueous drug dispersions to obtain a nanoparticulate dispersion comprises dispersing poorly soluble drug particles in a liquid dispersion medium” (Ryde, col. 9, ll. 39-41). 19. Ryde teaches that “[p]harmaceutical compositions according to the invention may also comprise one or more binding agents, filling agents, lubricating agents, suspending agents, sweeteners, flavoring agents, preservatives, buffers, wetting agents, disintegrants, effervescent agents, and other excipients. Such excipients are known in the art” (Ryde, col. 8, ll. 25- 30). 20. Ryde teaches that the “drug can be selected from a variety of known classes of drugs, including . . . analgesics . . . anti-inflammatory agents . . . antidepressants” (Ryde, col. 7, ll. 1-8). 21. Violante teaches that the “compositions of the invention may be administered by conventional routes which would be apparent to those skilled in the art, and in appropriate dosage form, such as sterile aqueous solution or suspension” (Violante, col. 5, ll. 17-20). Principles of Law “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “[A] prima facie case of obviousness exists when the claimed range and the prior art range do not overlap but are close enough such that one skilled in the art would have expected them to have the same properties.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). [W]here the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing Appeal 2011-012628 Application 11/979,253 9 novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on.… Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO‟s inability to manufacture products or to obtain and compare prior art products. In re Best, 562 F.2d 1252, 1254-55 (CCPA 1977). Analysis Liversidge teaches a liquid (FF 10) dosage form which comprises “surface modified nanoparticles comprising an NSAID” (Liversidge, col. 2, ll. 35-38; FF 2). Liversidge teaches the use of a surface stabilizer (FF 5) identical to those disclosed in the Specification (FF 3-4), as well as a particle size of 300 nm (FF 14). Ryde teaches that a variety of drug classes, including the classes of analgesics and anti-inflammatory drugs (FF 20) of which NSAIDs are a member, may be formulated in nanoparticles of 200 nm (FF 17). Violante teaches drug administration “in appropriate dosage form, such as sterile aqueous solution or suspension” (Violante, col. 5, ll. 17-20; FF 21). The Examiner finds that the viscosity of Liversidge inherently satisfies the requirement for a viscosity of less than 2000 mPa·s at a shear rate of 0.1 (l/s) (FF 12). Applying the KSR standard of obviousness to the findings of fact, we conclude that an ordinary artisan would have reasonably found it obvious to modify the particle size of Liversidge from “less than about 300 nm” (FF 14) Appeal 2011-012628 Application 11/979,253 10 or actual exemplified particle size of 216 nm (FF 15) to Ryde‟s slightly smaller particle size of “less than about 200 nm” (FF 17), since Liversidge teaches “that surface modified nanoparticles comprising an NSAID, e.g., naproxen, demonstrate reduced gastric irritation and/or a more rapid onset of action following oral administration” (Liversidge, col. 2, ll. 35-38; FF 2). We also conclude that the ordinary artisan would have reasonably modified Liversidge to use a sterile dosage form as taught by Violante, since a sterile dosage form would reduce the risk of contamination of the medication. Such a combination is merely a “predictable use of prior art elements according to their established functions.” KSR, 550 U.S. at 417. Appellants contend that the disclosure of the viscosity of a milling premix fails to teach or suggest the viscosity of the final product of the claimed invention. As one skilled in the art would understand, many factors affect the viscosity of a fluid, such as the compositions of the fluid, temperature, dilution factor and pressure. Therefore, one skilled in the art would not know the viscosity of the final product given the viscosity of a pre- milling intermediate product. (App. Br. 9.) We are not persuaded. The Examiner finds that regarding viscosity “Liversidge discloses a composition premix viscosity of as low as 1 centipoise . . . Liversidge discloses an average particle size which . . . overlaps with that of the instant application (see above) and discloses the same dispersion media . . . . As, claimed, applicants‟ composition contains the same components in the same configuration as the prior art” (Ans. 5-6; FF 12). The Examiners findings regarding the premix viscosity (FF 11-12), Appeal 2011-012628 Application 11/979,253 11 the particle sizes (FF 13-16), and the dispersion media (FF 9-10) are fully supported by the evidence of record. The Examiner reasonably relies upon the inherency doctrine to establish that the viscosity of the final products would be the same. Best, 562 F.2d at 1254. Appellants have provided no evidence to rebut the Examiner‟s position. Appellants contend that “one skilled in the art would understand that it is crucial to use the combination of a polymer and DOSS to achieve the synergistic effects” (App. Br. 10). Appellants contend that “one of skill in the art at the time the claimed invention was made would obtain a redispersible solid dose composition comprising a polymer and DOSS as the surface stabilizers. Such a composition is clearly distinguishable from Appellants‟ claimed low viscosity liquid dosage form” (id.). We are not persuaded. Liversidge teaches compositions with nanoparticles as low as 216 nm (FF 15) while Ryde teaches the use of nanoparticles “less than about 200 nm” (FF 17). In addition, the Specification‟s teaching that any size from 2000 nm to 50 nm would function, more than reasonably supports the Examiner‟s position that the use of Ryde‟s 200 nm particle size in Liversidge‟s liquid dosing composition represents a situation where 300 nm particles and 200 nm particles are close enough such that one skilled in the art would have expected them to have the same properties. See In re Peterson, 315 F.3d at 1329. Appellants contend that the “Examiner has failed to articulate any correlation between redispersion and low viscosity” (App. Br. 10). Appellants contend that the superior redispersion profile of Ryde‟s composition is irrelevant to the low viscosity of the claimed composition. Appeal 2011-012628 Application 11/979,253 12 Thus, one skilled in the art who intends to develop a liquid dosage form having low viscosity would not have any reason to look to a secondary reference which teaches how to improve the redispersion profile of a solid dosage form (App. Br. 10). We are not persuaded. Ryde is reasonably relied upon to demonstrate that nanoparticles of less than about 200 nm would have been expected to function in the administration of drug dosage forms (FF 16-20). Appellants contend that “the Examiner extracts the sterilization technique out of context and fails to consider the prior art as a whole to guide the modification of the primary reference, thereby to obtain the claimed invention” (App. Br. 12). Appellants contend that “[e]ven if the Examiner gives no patentable weight to the sterilization process, the claim require that the composition be sterile, which should be given proper weight” (id.). We are not persuaded. We agree with the Examiner that the mode of sterilization imposes no specific structural requirements on the structure of the dosage form. Instead, this limitation represents a method limitation in a product claim. See, e.g., Catalina Marketing International, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 810 (Fed. Cir. 2002) (“[D]isputed preamble language does not limit Claim 1-an apparatus claim. To hold otherwise would effectively impose a method limitation on an apparatus claim without justification”). We agree with Appellants that the claim does require the dosage form to be sterile, but Violante expressly teaches an “appropriate dosage form, such as sterile aqueous solution or suspension” (Violante, col. 5, ll. 17-20; Appeal 2011-012628 Application 11/979,253 13 FF 21). We agree with the Examiner that the ordinary artisan would reasonably have formulated the composition of Liversidge in view of Ryde and Violante in sterile form “because sterilization of liquid dosage forms mitigates microbial growth and thus extends shelf-life” (Ans. 6). The Examiner has established that using sterile dosage forms was known in the art and has provided a reason to modify Liversidge into a sterile dosage form. Conclusion of Law The evidence of record supports the Examiner‟s conclusion that Liversidge, Ryde and Violante render the composition of claim 1 obvious. B.-F. Double Patenting rejections “It is the claims, not the specification, that define an invention.... And it is the claims that are compared when assessing double patenting.” Ortho Pharmaceutical Corp. v. Smith, 959 F.2d 936, 943 (Fed. Cir. 1992). We are constrained to reverse the double-patenting rejections because the Examiner has not identified any claims in the copending applications which teach or suggest a “sterile” dosage form. We recognize that the Examiner finds, in the response to argument, that “Violante reference establishes that sterilization of liquid dosage forms was known in the art” (Ans. 20). However, Violante was not cited in any of the double patenting rejections and therefore cannot be relied upon to support these rejections. See In re Hoch, 428 F.2d 1341, 1342 n. 3 (CCPA 1970)(“Where a reference is relied on to support a rejection, whether or not in a „minor capacity,‟ there would appear to be no excuse for not positively including the reference in the statement of the rejection.”). Appeal 2011-012628 Application 11/979,253 14 SUMMARY In summary, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as obvious over Liversidge, Ryde, and Violante. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii), we also affirm the rejection of claims 2, 6-9, 11- 14, and 16-19 as these claims were not argued separately. We reverse the rejections of claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 3, 12, and 18 of US Application 10/420,927 and Bosch. claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 113-119 and 122-151 of US Application 10/878,623. claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 113-131 of US Application 11/093,149 (Ans. 10-11). claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 1-24 and 36-39 of US Application 10/701,064 and Bosch. claims 1, 2, 6-9, 11-14, and 16-19 on the ground of nonstatutory obviousness-type double patenting over claims 1-3, 5-8, 9-14, 17-22, 28-41, and 43-47 of US Application 10/697,716. Appeal 2011-012628 Application 11/979,253 15 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED cdc