Ex Parte Dennis et alDownload PDFPatent Trial and Appeal BoardMar 8, 201712446836 (P.T.A.B. Mar. 8, 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. 12/446,836 04/23/2009 James E. Dennis CWR-7701US PCT 9507 68705 7590 03/10/2017 TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP 1300 EAST NINTH STREET SUITE 1700 CLEVELAND, OH 44114 EXAMINER POPA, ILEANA ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 03/10/2017 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): rkline @ tarolli. com docketing@tarolli.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JAMES E. DENNIS, ARNOLD I. CAPLAN, and DAVID J. FINK Appeal 2016-002599 Application 12/446,836 Technology Center 1600 Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and JOHN G. NEW, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134(a) involving claims to a cell delivery composition. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Statement of the Case Background “Promises of cures of a wide variety of diseases or tissue injuries by specific replacement of damaged or diseased tissues by use of totipotent, pluripotent or multi potent stem cells is on the horizon in clinical practice” 1 Appellants identify the Real Party in Interest as Rigel Pharmaceuticals, Inc. (see App. Br. 2). Appeal 2016-002599 Application 12/466,697 (Spec. 12). “One of the comerstones/obstacles in implementing this technology is being able to direct the cells or tissue, engineered in vitro, to the precise in vivo site were repair as needed.” (Spec. 13). The Claims Claims 1—3, 6—20, and 22—30 are on appeal. Claim 1 is representative and reads as follows: 1. A cell delivery composition comprising: a progenitor cell; and a targeting moiety that binds to a target tissue, wherein said targeting moiety selectively directs the progenitor cell to the target tissue, wherein said targeting moiety is modified with a lipophilic moiety, and wherein a spacer moiety is inserted between the targeting moiety and the lipophilic moiety. The issues A. The Examiner rejected claims 1—3, 6—20, 22—26, and 30 under 35 U.S.C. § 103(a) as obvious over Caplan2 and Ruoslahti3 (Final Act. 3—4). B. The Examiner rejected claims 1—3, 6—20, and 22—30 under 35 U.S.C. § 103(a) as obvious over Caplan, Ruoslahti, Vellinga,4 and Kondo5 (Final Act. 5—8). 2 Caplan et al., WO 2004/084950 A2, published Oct. 7, 2004 (“Caplan”). 3 Ruoslahti et al., US 2003/0045476 Al, published Mar. 6, 2003 (“Ruoslahti”). 4 Vellinga et al., Spacers Increase the Accessibility of Peptide. Ligands Linked to the Carboxyl Terminus of Adenovirus Minor Capsid Protein IX, 78 J. Virology 3470-9 (2004) (“Vellinga”). 5 Kondo et al., Highly efficient delivery ofpi 6 antitumor peptide into aggressive leukemia/lymphoma cells using a novel transporter system, 3 Molecular Cancer Therapeutics 1623—30 (2004) (“Kondo”). 2 Appeal 2016-002599 Application 12/466,697 Because both rejections turn on the same issues and Appellants do not separately argue any of the dependent claims, we will consider the rejections together, and we select claim 1 as representative. The issue with respect to these rejection is: Does the evidence of record support the Examiner’s conclusion that Caplan and Ruoslahti render a spacer moiety obvious in a cell delivery composition? Findings of Fact 1. Claim 1 of Caplan is reproduced below: A cell delivery composition comprising: a) a progenitor cell; and b) a targeting moiety that binds to a target tissue, wherein said targeting moiety selectively directs the progenitor cell to the target tissue. (Caplan 45). 2. Caplan teaches methods of delivering a progenitor cell to a target tissue in a subject. . . . comprising: a) coating a progenitor cell with a linker; b) contacting the coated progenitor cell with a targeting moiety that binds to the linker and can then bind to the target tissue; and c) administering the progenitor cell complexed with the targeting moiety to a subject. (Caplan 2:7-11). 3. Caplan teaches in “certain embodiments, the progenitor cell is pre-coated with a linker, such as a protein G or protein A. Optionally, the linker is modified with a lipophilic moiety” (Caplan 2:25—27). 4. Caplan teaches the “targeting moiety is a fusion protein . . . [an] exemplary fusion protein comprises both an Fc fragment and a homing peptide” (Caplan 4:3—6). 3 Appeal 2016-002599 Application 12/466,697 5. Caplan teaches “to include a spacer (such as a polypeptide sequence or a chemical moiety) between a targeting moiety of the invention and the tag in order to facilitate construction or to optimize its structural constraints” (Caplan 25:22—25). 6. Ruoslahti teaches “a conjugate of the invention contains a homing peptide of the invention linked to a tag . . . If desired, an appropriate spacer can be positioned between the peptide and the support such that the ability of the heart homing peptide to interact with the target molecule is not hindered” (Ruoslahti || 92—93). 7. Vellinga teaches “labeling efficiency improved with increasing spacer length, suggesting that spacers lift and expose the ligand at the capsid surface” (Vellinga, abstract). 8. Kondo teaches a “Gly-Pro-Gly spacer, which serves to augment delivery of a cargo peptide” (Kondo, abstract). 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 Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” Id. at 417. Analysis We adopt the Examiner’s findings of fact and reasoning regarding the scope and content of the prior art as our own (Final Act. 3—8; FF 1—8) and agree that claims 1 and 30 are obvious over Caplan and Ruoslahti. We address Appellants’ arguments below. 4 Appeal 2016-002599 Application 12/466,697 Appellants separately argue each of the references, contending that Vellinga “does not teach or suggest that a-helical spacers can be used in a cell delivery composition of any kind”; that Kondo “does not teach or suggest that Gly-Pro-Gly spacers can be used in a cell delivery composition of any kind”; that Caplan “provide no teaching that a spacer can be inserted between the targeting moiety and the lipophilic moiety”; and that Ruoslahti does “not teach that a composition including a mammalian cell linked to a homing peptide modified with a lipophilic moiety, wherein a spacer moiety is inserted between the targeting moiety and the lipophilic moiety could selectively direct the cell to a target tissue” (App. Br. 8—12). We do not find these arguments persuasive, because they fail to address the teachings of the references in combination. “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., 800 F.2d 1091, 1097 (Fed. Cir. 1986). A reference “must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole.” Id. Caplan teaches coating a progenitor cell with a linker that connects to a targeting moiety (FF 2) where the targeting moiety may be modified with a lipophilic moiety (FF 3). While Caplan does not specifically teach a spacer between the targeting moiety and the lipophilic moiety, Caplan does teach the use of spacers to separate the targeting moiety from tags to eliminate structural constraints (FF 5). Ruoslahti teaches the use of spacers between targeting moieties and tags to avoid hindering the ability of the targeting moiety to interact with the target (FF 6). 5 Appeal 2016-002599 Application 12/466,697 We agree with the Examiner that the use of a spacer in Caplan’s composition would have been obvious to the ordinary artisan because “spacers were known and routinely used in the prior art to prevent steric hindrance and provide optimum interaction between targeting moieties and their targets” (Ans. 6). Appellants contend that one skilled in the art would not find it predictable and/or had a reasonable expectation of success in view of Caplan et al. and Ruoslahti et al. that a cell delivery composition, including a progenitor cell and a targeting moiety modified with a lipophilic moiety, wherein a spacer moiety is inserted between the targeting moiety and the lipophilic moiety, would selectively direct the progenitor cell to the target tissue. (App. Br. 15). Appellants contend that Caplan does “not discuss the use of spacers, let alone inserting a spacer between a lipophilic moiety and a homing peptide” (App. Br. 17). We are not persuaded because Caplan teaches “to include a spacer (such as a polypeptide sequence or a chemical moiety) between a targeting moiety of the invention and the tag in order to facilitate construction or to optimize its structural constraints” (FF 5) and Ruoslahti teaches that spacers ensure that the ability of a targeting “peptide to interact with the target molecule is not hindered” (FF 6). Thus, an ordinary artisan would have had a reasonable expectation of success because inclusion of a spacer between the targeting and lipophilic moieties taught by Caplan (FF 2—3) would have been expected to enhance the ability of the targeting moiety to interact with the target. “Obviousness does not require absolute predictability of success 6 Appeal 2016-002599 Application 12/466,697 . . . all that is required is a reasonable expectation of success.'1'’'’ In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (emphasis in original). We recognize, but find unpersuasive, Appellants’ argument that “Appellants] [are] under no obligation to submit evidence of nonobviousness” because “the Office Action has failed to produce a prima facie case of obviousness” (App. Br. 19). We find that the Examiner has established a prima facie case of obviousness based on the teachings of Caplan and Ruoslahti discussed already, including a reasonable expectation of success given the teachings of both references to use a spacer (FF 5—6). Not only do Appellants fail to provide any evidence rebutting the Examiner’s position, Appellants fail to provide any reasoning or logic as to why the ordinary artisan, motivated by Ruoslahti to use a spacer, would have had any difficulty in inclusion of a spacer as taught by both Caplan and Ruoslahti into a targeting peptide (FF 5—6). Appellants contend, with regard to claim 30, that “an ordinary skilled artisan would not modify the cell delivery composition of Caplan et al. by using an Fc/targeting moiety fusion protein linked to the lipophilic moiety in view of the teachings of Caplan” because “Caplan et al. does not teach or suggest that an Fc domain itself can be used as a spacer of any kind” (App. Br. 21). We are not persuaded. Caplan specifically teaches that an “exemplary fusion protein comprises both an Fc fragment and a homing peptide” (FF 4). Because the homing peptide represents the targeting moiety in Caplan, the Fc fragment is reasonably interpreted as functioning as a spacer in this disclosure itself. Even if the Fc fragment, a polypeptide sequence, does not 7 Appeal 2016-002599 Application 12/466,697 function as a spacer in this embodiment, Caplan teaches the spacer may be a polypeptide sequence (FF 5), rendering the use of the Fc fragment as a spacer obvious. Appellants contend that “using an Fc/targeting moiety fusion protein further fused/linked to the lipophilic moiety would destroy the intent, purpose, and/or function of an Fc domain tagged targeting moiety in a cell delivery composition disclosed by Caplan” (App. Br. 22). Appellants contend “that fusing an Fc domain to a lipophilic moiety and a targeting moiety would significantly change the principle of operation of [an] Fc domain tagged targeting moiety in a cell delivery composition disclosed by Caplan” (App. Br. 23). We do not find this argument persuasive and agree with the Examiner that: While it is true that the Fc fragment could be useful for isolation and purification, isolation and purification necessarily occur before attaching the lipophilic moiety. Thus, attaching the lipophilic moiety to the C-terminus of the Fc fragment cannot impede isolation and purification because attaching the lipophilic moiety occurs after the isolation and purification steps are completed. (Ans. 12). We also agree with the Examiner’s finding that it would be obvious to the skilled artisan to “attach a lipophilic moiety to the free C- terminus of the Fc fragment for inserting the targeting moiety together with the Fc spacer into the cell membrane such that the targeting moiety would be exposed unencumbered on the cell surface and able of efficiently interacting with its target tissue” (Ans. 11). 8 Appeal 2016-002599 Application 12/466,697 Conclusion of Law The evidence of record supports the Examiner’s conclusion that Caplan and Ruoslahti render a spacer moiety obvious in a cell delivery composition. SUMMARY In summary, we affirm the rejection of claims 1 and 30 under 35 U.S.C. § 103(a) as obvious over Caplan and Ruoslahti. Claims 2, 3, 6— 20, and 22—26 fall with claims 1 and 30. We affirm the rejection of claims 1 and 30 under 35 U.S.C. § 103(a) as obvious over Caplan, Ruoslahti, Vellinga, and Kondo. Claims 2, 3, 6—20, and 22—29 fall with claims 1 and 30. 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 9 Copy with citationCopy as parenthetical citation