10795132 (P.T.A.B. Mar. 27, 2013)

Ex Parte Sawhney et al

Patent Trial and Appeal BoardMar 27, 2013

10795132 (P.T.A.B. Mar. 27, 2013)

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. 10/795,132 03/05/2004 Amarpreet S. Sawhney 3516.06US02 9566 62274 7590 03/27/2013 DARDI & HERBERT, PLLC Moore Lake Plaza, Suite 205 1250 East Moore Lake Drive Fridley, MN 55432 EXAMINER MAEWALL, SNIGDHA ART UNIT PAPER NUMBER 1612 MAIL DATE DELIVERY MODE 03/27/2013 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 AMARPREET S. SAWHNEY, PETER G. EDELMAN, and STEVEN L. BENNETT __________ Appeal 2011-013610 Application 10/795,132 Technology Center 1600 __________ Before TONI R. SCHEINER, STEPHEN WALSH, and ERICA A. FRANKLIN, Administrative Patent Judges. SCHEINER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 from the rejection of claims directed to a system, method, and kit for forming a biodegradable tissue- adherent covalently-crosslinked water-insoluble hydrogel in situ. The claims have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. Appeal 2011-013610 Application 10/795,132 2 STATEMENT OF THE CASE Claims 56, 66, 67, 78, 79, 81, 84, 90, 91, and 93-95 are pending and on appeal. Claims 1-55, 57-65, 68-77, 80, 82, 83, 85-89, 92, and 96 have been canceled (Claims Appendix). Hydrogels are “used as sealants for tissue fluid leaks, as adherent drug delivery depots, [and] as means for augmenting and/or supporting tissue” (Spec. 1: 10-12). According to the Specification, “[i]n situ therapy has primarily focused on transformation of precursor solutions into solids within a patient’s body . . . by a variety of means, including precipitation, polymerization, [and] crosslinking” (id. at 1: 17-19). The present invention is directed to “medical sealant compositions that . . . comprise a mixture of two or more individual dehydrated precursors, which activate upon exposure to fluid in a physiological environment” (id. at 7: 6-9). “Upon exposure, dissolution and nearly simultaneous crosslinking of . . . [the] dehydrated precursors occurs, thus forming an insoluble hydrogel implant, which is preferably biodegradable” (id. at 7: 9-11). The precursors “may be administered directly to an open wound site or may be dispensed using . . . a powder atomization or aerosolization system, or a needle-less injector” (id. at 7: 14-17). Claims 56, 78, and 95 are representative of the subject matter on appeal: 56. A system for in situ therapy comprising: an applicator selected from the group consisting of a powder atomization system and a needle-less injector capable of delivering a powder; and the powder, with said powder comprising at least two substantially dry lyophilized hydrogel precursors compounded with each other in powder form that are water soluble and have functional groups for forming Appeal 2011-013610 Application 10/795,132 3 crosslinks with each other, wherein the precursors, upon exposure to an aqueous fluid in a physiological environment, dissolve and substantially simultaneously crosslink with each other to thereby form a tissue-adherent covalently-crosslinked water-insoluble biodegradable hydrogel in situ. 78. A method of forming a water-insoluble hydrogel in situ comprising: providing at least two substantially dry hydrogel precursors compounded together and prepared by lyophilization to form a powder, wherein the dry hydrogel precursors are water soluble and have functional groups for forming covalent bonds, wherein covalent bonding of the functional groups causes the at least two precursors to be covalently crosslinked with each other to thereby form a hydrogel in situ upon exposure to an aqueous physiological fluid; and delivering the powder without a solvent to an implantation site in situ in a patient to expose the precursors to aqueous physiological fluids from the implantation site to cause dissolution and crosslinking of the precursors with each other to thereby form a covalently-crosslinked water-insoluble biodegradable hydrogel adherent to the implantation site, wherein the dissolution and the crosslinking of the precursors is substantially simultaneous. 95. A kit comprising the applicator and the powder of claim 78. Claims 56, 66, 67, 78, 79, 81, 84, 90, 91, and 93-95 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Rhee et al. (Rhee) (US 5,874,500, February 23, 1999), Rhee et al. (Rhee II) (5,643,464, July 1, 1997), and Etter (US 2001/0036480 A1, November 1, 2001). FINDINGS OF FACT 1. Rhee discloses a method “for augmenting soft or hard tissue within the body of a mammalian subject” (Rhee, col. 2, ll. 65-66), wherein “a first synthetic polymer containing two or more nucleophilic groups and a second synthetic polymer containing two or more electrophilic groups are administered simultaneously to a tissue site . . . and the reaction mixture is allowed to crosslink in situ” (id. at col. 2, l. 66 - col. 3, l. 4). Appeal 2011-013610 Application 10/795,132 4 2. According to Rhee, “[p]olymers containing multiple nucleophilic groups are generally not water-reactive and can therefore be stored in aqueous solution” (Rhee, col. 10, ll. 60-62), but “polymers containing multiple electrophilic groups will . . . react with water,” and are therefore “generally stored and used in sterile, dry form to prevent the loss of crosslinking ability due to hydrolysis” (id. at col. 10, ll. 45-48). 3. Rhee discloses that the first and second synthetic polymers “may be contained within separate barrels of a dual-compartment syringe” (Rhee, col. 13, ll. 52-53), so that “the two synthetic polymers do not actually mix until the point at which the two polymers are extruded from the tip of the syringe needle into the patient’s tissue” (id. at col. 13, ll. 53-56). Rhee teaches that “[t]his allows the vast majority of the crosslinking reaction to occur in situ, avoiding the problem of needle blockage which commonly occurs if the two synthetic polymers are mixed too early and crosslinking . . . is already too advanced prior to delivery” (id. at col. 13, ll. 56-61). 4. Rhee does not disclose any instances where a mixture of two different dry polymer precursors is administered to a tissue site, and allowed to dissolve and crosslink in situ (see, e.g., Examples 1-5). 5. Rhee II discloses a method of producing strong, evenly crosslinked hydrogels for use in tissue augmentation (Rhee II, col. 1, ll. 22- 26; col. 3, ll. 13-19). The method comprises mixing a lyophilized (i.e. dry) crosslinking agent with an aqueous suspension of collagen (or some other biocompatible polymer) and delivering the mixture to a tissue site (by syringe or compressed air injector) where cross-linking proceeds primarily in situ (Rhee II, col. 3, ll. 13-19, 42-45; col. 3, l. 66 - col. 4, l. 9; col. 6, ll. 19-21; col. 14, ll. 54-62). Appeal 2011-013610 Application 10/795,132 5 6. Rhee II discloses more than one sterile, dry crosslinking agent, “such as a synthetic hydrophilic polymer or a carbodiimide” (Rhee II, col. 7, ll. 41-42), but does not disclose any instances where two different dry polymers are compounded together, or even used together to form a hydrogel. DISCUSSION The Examiner finds that Rhee discloses cross-linked compositions comprising “a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups” (Ans. 5). The Examiner further finds that Rhee’s compositions are “used to affect adhesion between two surfaces, [and] to effect tissue augmentation” (id.), and that “the two polymers can be administered simultaneously to the tissue site in need of augmentation and . . . allowed to cross-link in situ” (id. at 7). The Examiner further finds that Rhee’s second polymer containing electrophilic groups “is usually stored and used in sterile dry form to prevent [the] loss of crosslinking ability due to hydrolysis which occurs in an aqueous media” (id.),” but concedes that “the reference does not teach lyophilized dry precursors” (id.). The Examiner finds that Rhee II discloses a method of making sterile, storage-stable lyophilized cross linking agents for use in biocompatible polymers for tissue augmentation (id. at 8). The Examiner concludes that it would have been obvious for one of ordinary skill in that art to have utilized dry lyophilized precursors of electrophile and nucleophiles for forming cross linked water insoluble biodegradable hydrogel once administered to physiological Appeal 2011-013610 Application 10/795,132 6 sites of human body because [Rhee II] teaches that lyophilized cross linking agents provide more stability over [a] long period of time and also . . . provides a means for delivering the sterile polymer to tissue augmentation site (id.). Appellants contend that even though Rhee teaches that one of its polymer precursors “might be stored as a powder, it is dissolved in solution before application to the site” (App. Br. 9), and “Rhee does not teach delivery of dry powders to the tissue site” (id.) whereby dissolution and crosslinking of the dry precursors occurs upon exposure to physiological fluids present at the tissue site. Appellants contend that Rhee II does not disclose this aspect of the invention either, but combines a dry crosslinking agent with an aqueous suspension of collagen prior to or upon delivery to the tissue site. Finally, Appellants contend that Etter is directed to aerosol drug formulations for pulmonary delivery, and “does not make-up for the defects of Rhee and Rhee II” (id.). We agree with Appellants that the mere fact that Rhee and Rhee II both discuss the storage stability and convenience of dry polymers and/or crosslinking agents would not have led one of ordinary skill in the art to compound two different dry hydrogel precursors and deliver them to a tissue site for dissolution and crosslinking upon exposure to aqueous physiological fluids. Moreover, while Rhee II teaches that using a lyophilized (i.e. dry) crosslinking agent produces a strong, evenly crosslinked hydrogel, the dry crosslinking agent is always mixed with an aqueous suspension of collagen, or some other biocompatible polymer (FF5). What is lacking from the prior art is the fundamental concept of delivering a dry precursor directly to a tissue site where it rehydrates in Appeal 2011-013610 Application 10/795,132 7 physiological fluid already present at the site and begins crosslinking to form a hydrogel in situ - much less the concept of delivering two different precursors which will crosslink with each other upon dissolution. Moreover, with respect to the system and kit claims (e.g., claims 56 and 95 1 ), the Examiner has not explained why one of ordinary skill in the art would have had a reason to compound two different dry hydrogel precursors together to form a powder, given the art of record. SUMMARY The rejection of claims 56, 66, 67, 78, 79, 81, 84, 90, 91, and 93-95 under 35 U.S.C. § 103(a) as unpatentable over Rhee, Rhee II, and Etter is reversed. REVERSED cdc 1 We agree with Appellants that kit claim 95 would be “properly dependent on claim 56,” rather than claim 78 (App. Br. 14).