Ex Parte Kuzma et alDownload PDFPatent Trial and Appeal BoardJun 22, 201612814286 (P.T.A.B. Jun. 22, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/814,286 06/11/2010 Petr KUZMA 105159 7590 06/24/2016 Ratner Prestia P.O. Box 980 Valley Forge, PA 19482 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. EPSI-106US1 8925 EXAMINER REYNOLDS, FRED H ART UNIT PAPER NUMBER 1675 NOTIFICATION DATE DELIVERY MODE 06/24/2016 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): PCorrespondence@ratnerprestia.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte PETR KUZMA and STEPANIE DECKER Appeal2014-005101 Application 12/814,286 Technology Center 1600 Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and JOHN G. NEW, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to a method of delivering octreotide to a subject by implanting a device with a hydrophilic polymer and octreotide. Appellants appeal from the Examiner's final rejection of claims 1, 3, and 5-20 under 35 U.S.C. § 103 as obvious over the combined cited prior art. We have jurisdiction under 35 U.S.C. § 134. The rejections are affirmed. STATEMENT OF CASE The claims stand rejected by the Examiner as follows: Appeal2014-005101 Application 12/814,286 Claims 1, 3, and 5-19 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in view of Bodmer1 and Kuzma. 2 Final Rej. 3. Claims 1 and 20 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in view of Bodmer, Kuzma, and Repka. 3 Final Rej. 6. Non-statutory obviousness double patenting rejections were withdrawn by the Examiner. Id. at 2. A new ground of rejection of claim 20 under 35 U.S.C. § 112 as failing to describe with the written description was made in the Final Rejection. Id. at 5---6. In the Advisory Action before the Appeal Brief was filed, the Examiner indicated the rejection had been overcome. Advisory Action (Sept. 11, 2013). Claim 1 is the only independent claim on appeal and reads as follows: 1. A method of delivering octreotide to a subject with a substantially zero-order release profile over an extended period of time, but no less than about six months, the method compnsmg: subcutaneously implanting in the subject at least one implantable device; \'I/herein: the at least one implantable device comprises a composition comprising octreotide encased in a hydrophilic polymer, wherein the hydrophilic polymer comprises a co- polymer obtained from the co-polymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers; and the implantable device is implanted in a dry state, such that the subject receives on a daily basis over a period of at least about six months dose amounts of octreotide, which are effective to treat the subject. 1 Bodmer et al., US 5,688,530, issued Nov. 18, 1997 ("Bodmer") 2 Kuzma et al., US 5,266,325, issued Nov. 30, 1993 ("Kuzma"). 3 Repka and McGinity, Influence of Vitamin E TPGS on the properties of hydrophilic films produced by hot-melt extrusion, 202 International Journal of Pharmaceutics 63-70 (2000) ("Repka"). 2 Appeal2014-005101 Application 12/814,286 OBVIOUSNESS IN VIEW OF BODMER AND KUZMA Claim 1 Claim 1, the only independent claim on appeal, is directed to a method of delivering octreotide to a subject. Octreotide is an octapeptide with the structure shown in paragraph 4 7 of the Specification. It is an analog of the hormone somatostatin. Bodmer, col. 1, 11. 12-14. According to the Specification, octreotide was a commercially available drug prior to the invention which was used for long-term maintenance therapy in acromegalic patients and "long-term treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and profuse water diarrhea associated with VIP-secreting tumors." Spec. i-f 7. The claim requires the octreotide to be encased in a hydrophilic polymer obtained from the co-polymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers. The monomers can be methylacrylates (claim 3), such as 2-hydroxyethyl methacrylate and hydroxypropyl methacrylate monomers (claims 17-19). The claimed method has one step of subcutaneously implanting "one implantable device" which comprises a composition comprising the octreotide encased in the hydrophilic polymer. The device is implanted in the dry state. The octreotide has a "zero-order release profile over an extended period of time" and is delivered over at least about six months. 3 Appeal2014-005101 Application 12/814,286 Rejection The Examiner found that Bodmer describes microparticles comprising octreotide and a polymer of poly(lactide-co-glycolide) glucose. Final Rej. 3. The Examiner found that the particles were implanted ("injected") into rabbits as required by the claim ("method of delivering octreotide to a subject"). Id. The Examiner found that Bodmer does not teach the zero- order release of octreotide over a six month period nor implanting the particles in a dry state. Id. However, the Examiner found that Kuzma describes implants made with the hydrophilic ethylenically unsaturated monomers hydroxyethylmethacrylate and hydroxypropylmethacrylate (id.), the same monomers which are claimed, and their use to release leutinizing hormone releasing hormone ("LHRH") over a six month period ("over 200 days"). Id. The Examiner also found that Kuzma describes implanting the implant in a dry state as required by claim 1. Id. at 4. The Examiner determined it would have been obvious to one of ordinary skill in the art to utilize Kuzma's implant comprising hydrophilic ethylenically unsaturated monomers to achieve release of therapeutically effective amounts of octreotide for longer periods of time. Id. at 3--4. Appellants contend that the modification proposed by the Examiner would change the principle of operation of Bodmer and make it unsuitable for its intended purpose. Br. 4. Specifically, Appellants state that Bodmer's polymer is biodegradable and provides a first-order order release profile of the octreotide. Id. at 4--5. In contrast, Appellants argue that Kuzma's polymer is a non-biodegradable polymer which exhibits a zero-order release 4 Appeal2014-005101 Application 12/814,286 profile. Id. at 5. Appellants provided a declaration by Scot Thoroughman,4 an employee of the patent owner (Appeal Br. 2; Thoroughman Deel. i-f 2), 5 who attested to these facts. Mr. Thoroughman further stated that "substituting the non- biodegradable reservoir implant of Kuzma for the biodegradable matrix depot implant of Bodmer would not have been obvious to one of ordinary skill in the art as both the technology used to develop, and the principle of operation for, the implant classifications differ significantly." Thoroughman Deel. i-f 8. Mr. Thoroughman explained that the release of a "principle agent" (i.e., a drug, such as octreotide) from a biodegradable matrix, as described in Bodmer has a first-order release profile which "sacrifice[s] the duration of treatment and the consistency of release rate for the benefits of ease of administration and absence of the requirement to retrieve the implant after the treatment period." Id. Mr. Thoroughman stated that non- biodegradable implants "exhibit a much better approximation of a zero-order release profile allowing the release of the principle agent to be substantially constant." Id. After explaining what governs the release from a non- biodegradable implant, Mr. Thoroughman stated that such implants "sacrifice ease of administration and the requirement for post-treatment surgical implant retrieval for improvements in the duration of treatment and consistency of release rate." Id. Based on these differences, Mr. Thoroughman concluded: 4 Declaration of Scot Thoroughman, dated August 30, 2013. 5 Mr. Thoroughman stated that he holds "the position of Director AR&D, a senior role responsible for analytical characterization of non-biodegradable implant technologies within Endo's Implant Drug Delivery group." Thoroughman Deel. i-f 2. 5 Appeal2014-005101 Application 12/814,286 Id. Substituting a non-biodegradable implant membrane for a biodegradable implant membrane, as required in the modification suggested by the Examiner, would therefore change the principle of operation of the implant of Bodmer because the active principle would be released in a completely different manner (i.e. zero-order release profile vs. first-order release profile) leading to release rate characteristics unlikely to yield a viable extended release drug product. Mr. Thoroughman did not provide persuasive evidence that the claimed subject matter would not have been obvious to one of ordinary skill in the art. It is not disputed by the Examiner that polymers utilized by Bodmer and Kuzma have different release profiles as testified by Mr. Thoroughman. Answer 6. However, as the Examiner points out, both publications "have the intended purpose of improving the pharmacokinetics of therapeutic drugs, with the principle of operation controlled release from a polymeric implant." Id. Utilizing Kuzma's implant for the delivery of octreotide would have been obvious to obtain the sustained release benefits of Kuzma's mixture of ethylenically unsaturated monomers. Kuzma, col. 5, 11. 10-13; col. 6, 11. 49-52. As stated in KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007), [I]f a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill . . . . [A] court must ask whether the improvement is more than the predictable use of prior art elements according to their established functions. Appellants have not provided evidence that utilizing Kuzma's implant to deliver octreotide is anything more than the predictable use of a prior art element according to its established function. Kuzma teaches that its 6 Appeal2014-005101 Application 12/814,286 implant, which comprises the same polymer that is claimed, can be used to deliver polypeptide hormones, including short-chain peptides. Kuzma, col. 17, 1. 32 to col. 19, 1. 4. Octreotide is also a peptide. Consequently, the skilled worker would have had a reasonable expectation that it would be effectively released from Kuzma's polymer. Appellants have not provided persuasive evidence to the contrary. Mr. Thoroughman's testimony that utilizing Kuzma's implant to release octreotide would not have been obvious because it changes the principle of operation of Bodmer does not fully take into consideration that Kuzma describes its implant for peptides, that octreotide is a peptide, and further that Kuzma's polymer has advantageous sustained release characteristics. Thus, while the release profiles may be different, the skilled worker would have had reason to have altered the profile in Bodmer to achieve the beneficial release characteristics described in Kuzma. Consequently, the preponderance of the evidence does not support Mr. Thoroughman' s testimony. The rejection of claim 1 is affirmed. Claims 3 and 5-19 were not argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(iv). OBVIOUSNESS IN VIEW OF BODMER, KUZMA, AND REPKA Claim 20 depends from claim 1 and further recites that "the hydrophilic polymer comprises Vitamin E TPGS." The Examiner found Repka teaches vitamin E TPGS as a plasticizer that allows polymers to be more flexible. Final Rej. 7. The Examiner determined it would have been obvious to have included vitamin E TPGS in Kuzma's implant to make the implant more flexible and make processing conditions easier. Id. 7 Appeal2014-005101 Application 12/814,286 Appellants make the same unpersuasive arguments as they did for Bodmer and Kuzma. Accordingly, the rejection of claims 1 and 20 is affirmed. TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv). AFFIRMED 8 Copy with citationCopy as parenthetical citation