Ex Parte Caplan et alDownload PDFPatent Trial and Appeal BoardJul 6, 201710550590 (P.T.A.B. Jul. 6, 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. 10/550,590 06/01/2006 Arnold Caplan CWR-7781PCT/US 1634 68705 7590 07/10/2017 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 07/10/2017 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 ARNOLD I. CAPLAN and JAMES E. DENNIS Appeal 2015-003611 Application 10/550,5901 Technology Center 1600 Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and JEFFREY N. FREDMAN, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134(a) involves claims 1, 2, 4, 6, 8, 9, 11, 13-15, 26, 29, 39, 41, 45, 47, 48, 50, 52, 54—56, 67, 70, 80, 82, 85, 190, and 191 (App. Br. 2).2 Examiner entered a rejection under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellants identify the real party in interest as “Case Western Reserve University” (App. Br. 2). 2 Pending “[cjlaims 3, 16-18, 20-25, 32-38, 46, 57-59, 61-66, 73-79, 84, 86- 89, 96-97, 99, 101, 103-105, 107, 109-110, 112, 114-119, 121-127, 130, 133-140, 142-143, 145, 147-149, 151, 153-154, 156, 158-163, 165-171, 174, 177-184, 186, [and] 188-189[] [stand] withdrawn” from consideration (App. Br. 2). Appeal 2015-003611 Application 10/550,590 STATEMENT OF THE CASE Appellants disclose “compositions and methods for delivering progenitor cells to target tissues” (Spec. 2). Claim 1 is representative and reproduced below: 1. A composition for targeting a progenitor cell to a target tissue 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 progenitor cell is linked to said targeting moiety, wherein said targeting moiety is modified with a lipophilic moiety or said progenitor cell is pre-coated with a linker, and wherein said linked targeting moiety enhances adherence of the progenitor cell to the target tissue when administered to a target tissue injury site and wherein the targeting moiety does not adversely affect progenitor cell viability, mitotic potential, and phenotype. (App. Br. 32.) 2 Appeal 2015-003611 Application 10/550,590 The claims stand rejected as follows: Claims 1, 2, 4, 6, 8, 9, 11, 13-15, 26, 29, 39, 41, 45, 47, 48, 50, 52, 54—56, 67, 70, 80, 82, 85, 190, and 191 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Logtenberg,3 Caplan,4 Colsky,5 Kim,6 Thomas,7 and Simmons.8 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? 3 Logtenberg et al, WO 00/23570 Al, published Apr. 27, 2000. 4 Arnold I. Caplan and Scott P. Bruder, Mesenchymal stem cells: building blocks for molecular medicine in the 21st century, 7 TRENDS IN Molecular Medicine 259-264 (2001). 5 Arthur S. Colsky and James S. Peacock, Palmitate-derivatized antibodies can function as surrogate receptors for mediating specific cell-cell interactions, 124 Journal of Immunological Methods 179-187 (1989). 6 Stanley A. Kim and James S. Peacock, The use of palmitate-conjugated protein A for coating cells with artificial receptors which facilitate intercellular interactions, 158 Journal of Immunological Methods 57— 65 (1993). 7 J Terrig Thomas et al., Cartilage collagens: strategies for the study of their organisation and expression in the extracellular matrix, 53 Annals of the Rheumatic Diseases 488-496 (1994). 8 Paul J. Simmons et al., Isolation, Characterization and Functional Activity of Human Marrow Stromal Progenitors in Hemopotesis, Advances in Bone Marrow Purging and Processing: Fourth International Symposium 271—280 (1994). 3 Appeal 2015-003611 Application 10/550,590 FACTUAL FINDINGS (FF) FF 1. Logtenberg discloses, inter alia, a method of inserting lipid-modified proteinaceous molecules into the membrane of a cell (Logtenberg 3: 23—29; Ans. 3). FF 2. Logtenberg discloses that its method “appears to be generally applicable to all cell types” (Logtenberg 5: 19-20; see also id. at 12: 11 (Logtenberg’s “cell may be any type of prokaryotic or eukaryotic cell”); Ans. 3). FF 3. Logtenberg discloses that “[o]ne of the most prominent applications of [its method] lies in the field of cell therapy as a strategy for the treatment of human diseases” (Logtenberg 4: 29—31; see also id. at 2: 24—25 (“Cell therapy is a strategy for the treatment of many diseases. The aim of cell therapy is to replace or repair damaged tissue or organs or to enhance the biological function of cells”); Ans. 3). FF 4. Logtenberg’s method provides recipient cells with, inter alia, the ability to recognize a target (Logtenberg 4: 7—11; Ans. 3). FF 5. Logtenberg’s proteinaceous molecules may be “receptors, co receptors, (membrane-bound) ligands,” “single chain variable fragments (scFv),” or “antibodies, fragments derived from antibodies such as fragment antigen binding (FAB) fragments” (Logtenberg 8: 30—32 and 9: 7 and 25— 26; Ans. 3). FF 6. Logtenberg discloses: In a preferred embodiment [the] lipid-modified proteinaceous molecules provide the particles with membranes derived from cells with a new target cell specificity. Such specificity may be added through, for example, a scFv molecule with a specificity 4 Appeal 2015-003611 Application 10/550,590 for an antigen on the surface of a cell type previously not belonging to the target cell pool of said particle. (Logtenberg 14: 8—14; Ans. 3.) FF 7. Logtenberg’s method allows [for] the rapid and efficient insertion of lipid-tagged (LT) proteins into the membrane of prokaryotic and eukaryotic cells. The procedure appears to be applicable to most eukaryotic cell types including freshly isolated cell populations. LT-scFv antibody fragments inserted into cell membranes where shown to remain fully functional, capable of binding soluble and membrane-bound molecules expressed by other cells. (Logtenberg 15: 31—16: 4; see generally id. at 24—25; Ans. 4.) FF 8. Logtenberg discloses that “[t]he insertion of LT-scFv’s [into cells] did not affect cell proliferation [], nor cell viability” (Logtenberg 34: 8—10; 4; see generally id. at 39: 13—20; see also Ans. 3—4). FF 9. Examiner finds that while Logtenberg discloses “tissue repair, [it does] not specifically teach injecting the cell directly into the tissues such as cartilage or bone, nor do they teach [] a mesenchymal stem cell (MSC)” (Ans. 4). FF 10. Caplan discloses that “the multi-lineage potential of MSCs, their exquisite sensitivity to specific signaling molecules, and their relative ease of handling in vitro, they are a potentially powerful tool in tissue engineering. This approach has been employed, using animal models, for bone[ ], cartilage[ ], tendon[ ], marrow stroma[ ] and muscle[ ] repair and regeneration” (Caplan 261 (endnotes omitted); Ans. 4). FF 11. Caplan discloses that “[b]oth animal and human MSCs in culture have been successfully transduced with exogenous genes using several 5 Appeal 2015-003611 Application 10/550,590 different vectors without an apparent defect of their stem cell properties[ ]” (Caplan 261 (endnotes omitted); Ans. 4). FF 12. Caplan discloses that MSCs could be injected into diarthrodial joint spaces to contribute to repair or regeneration of meniscal or articular cartilage[ ] Methods to stimulate expression of specific cell surface ligands, either natural or engineered, that can mediate selective attachment to known receptors in target tissues of interest will be of considerable clinical benefit. (Caplan 262 (endnotes omitted); see id. (“targeting the infused cells to specific tissue locations could have a large impact on future therapeutic uses of MSCs for other diseases”); Ans. 4.) FF 13. Examiner finds that “[ajlthough [the combination of] Logtenberg [] and Caplan [] teach coating their cells with lipid-modified antibodies, they do not specifically teach palmitoylated antibodies or attaching the antibody via a palmitoylated protein A linker” and relies on Colsky and Kim to make up for this deficiency in the combination of Logtenberg and Caplan (Ans. 5). FF 14. Colsky discloses “a method for incorporating palmitate-derivatized antibody molecules onto cell membranes where they function as [‘Jsurrogate receptors’ (SR) for mediating specific cellular interactions” and, thereby, enable the palmitate-derivatized antibody molecules “to cooperate with endogenous target recognition structures in receptor-ligand interactions at the cell-cell interface” (Colsky, Abstract; see id. at 180; Ans. 5). FF 15. Kim discloses “[a] method [] in which palmitate-conjugated protein A (pal-protein A) incorporated onto cell membranes is used to anchor antibodies on the surface of cells,” wherein “cells can be coated with antibody (Ab) molecules of a desired specificity that can serve as artificial receptors for soluble or cell surface antigens (Ags)” (Kim, Abstract; see id. 6 Appeal 2015-003611 Application 10/550,590 at 58 (“The increased avidity supplied by [Kim’s] artificial receptors mediated a high level of heterotypic cell-cell conjugation. The method presented here should be broadly applicable to many studies where it is desired to target specific molecules to cell surfaces or to induce specific intercellular interactions”); Ans. 5). FF 16. Examiner finds that “[although [the combination of] Logtenberg [], Caplan [,] Colsky [], and Kim teach specific delivery to cartilage by using antibody-coated MSCs, they do not specifically teach using anti-collagen II antibodies []” and relies on Thomas to disclose “that collagen II is a cartilage-specific collagen” (Ans. 5, citing Thomas 488). FF 17. Examiner relies on Simmons to disclose the marker “Stro-1,” which is expressed on MSCs (Ans. 4, citing Simmons 273). FF 18. Beauchamp discloses “that the majority of transplanted muscle precursor cells [] die in host muscle and only a minority (less than 1 %) are responsible for new muscle formation” (App. Br. 21, citing Beauchamp9 1115). ANALYSIS Based on the combination of Logtenberg, Caplan, Colsky, Kim, Thomas, and Simmons, Examiner concludes that, at the time Appellants’ invention was made, it would have been prima facie “obvious to use the method of Logtenberg [] with modified MSCs [the “progenitor cell” of claim 1 modified with the antibodies or protein serving as the recited “targeting moiety”] and administer the modified MSCs directly into the damaged bone 9 Jonathan R. Beauchamp et al., Dynamics of Myoblast Transplantation Reveal a Discrete Minority of Precursors with Stem Cell—like Properties as the Myogenic Source, 144 Journal of Cell Biology 1113-1121 (1999). 7 Appeal 2015-003611 Application 10/550,590 or cartilage to achieve the predictable result of specifically targeting the cells to the damaged cartilage or bone with the purpose of regenerating the damaged cartilage or bone” (Ans. 4). In this regard, Examiner concludes: It would have been obvious to one of skill in the art, at the time the invention was made, to modify the composition of Logtenberg [] and Caplan [] by using palmitoylated antibodies or a palmitoylated protein A linker to achieve the predictable result of coating the cells with antibodies as targeting agents. (Ans. 5.) Examiner further concludes: [I]t would have been obvious to one of skill in the art, at the time the invention was made, to use an anti-collagen II antibody in the method [suggested by the combination of Logtenberg, Caplan, Colsky, and Kim] to achieve the predictable result of targeting their MSCs to the cartilage tissue. (Ans. 5—6.) We are not persuaded by Appellants contention that Logtenberg: [Does] not disclose a proteinaceous molecule (e.g., an antibody) can be used to target the cell or lymphocyte to a site of injury when administered to a site of injury, let alone enhance adherence of the progenitor cell to the target tissue while not adversely affecting progenitor cell viability, mitotic potential, and phenotype. (App. Br. 13). Logtenberg discloses a method of inserting lipid-modified proteinaceous molecules, such as lipid-modified antibodies or antibody fragments, into the membrane of a cell, wherein the method is “generally applicable to all cell types” (LL 1, 2, and 5—8). In this regard, Logtenberg discloses that the insertion of lipid-modified antibodies into the membrane of cells provides the modified cells with the ability to specifically bind target cells (LL 6 and 7), the same purpose of the “targeting moiety” of claim 1. Logtenberg further discloses that “[t]he insertion of LT-scLv’s [into cells] 8 Appeal 2015-003611 Application 10/550,590 did not affect cell proliferation [], nor cell viability” (FF 8). In addition, Caplan discloses that MSCs are relatively easy to handle and may be manipulated “without an apparent defect of their stem cell properties” (FF 10—11 (endnote omitted)). Colsky and Kim further support Examiner’s finding that the modification of a cell with an antibody, according to the combination of Logtenberg, Caplan, Colsky, Kim, and Thomas is broadly applicable and provides a mechanism to specifically target cells to a desired location, such as cartilage (FF 14—16). Therefore, we are not persuaded by Appellants contention “that without the experimental data disclosed in the[ir] [Specification, one having skill in the art could not have found it predictable that attaching proteinaceous molecules to progenitor cells as recited in claim 1 would not adversely affect progenitor cell viability, mitotic potential, and phenotype of the progenitor cells []” (App. Br. 22, citing Specification 39: 23—28; 43: 8—9, 13—14, and 17—25; and Figs. 2—4). In re O’Farrell, 853 F.2d 894, 903—904 (Fed. Cir. 1988) (“Obviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success”). A reference disclosure is available for all that it discloses and suggests to one of ordinary skill in the art. In re Lamberti, 545 F.2d 747, 750 (CCPA 1976). Therefore, for the foregoing reasons, we are not persuaded by Appellants’ contentions regarding “homing” or the difference between lymphocytes and progenitor cells (App. Br. 13—15 and 22—24; see also id. at 17-20; Reply Br. 3-4). For the foregoing reasons, we are not persuaded by Appellants’ contention that the combination of Logtenberg, Caplan, Colsky, Kim, and Thomas fails to provide a person of ordinary skill in this art with a 9 Appeal 2015-003611 Application 10/550,590 reasonable expectation of successfully preparing a composition comprising a progenitor cell and a targeting moiety, within the scope of Appellants’ claimed invention, wherein “a proteinaceous molecule linked to a progenitor cell could enhance adherence of a progenitor cell to a target tissue site when administered to a target tissue injury site and not adversely affect progenitor cell viability, mitotic potential, and phenotype” (App. Br. 15; see also id. at 16 (Caplan alone, does not suggest: “a means for increasing the efficiency of mesenchymal stem cell engraftment;” “a composition having a progenitor cell linked to a targeting moiety, modified with a lipophilic moiety, capable of targeting target tissue at a target tissue injury site;” or “that such compositions would not adversely affect progenitor cell viability, mitotic potential, and phenotype of a progenitor cell”); id. at 24; Reply Br. 2 and 3— 4; cf. FF 1—16; Ans. 4—6). In re O’Farrell, 853 F.2d at 903. For the foregoing reasons, we are not persuaded by Appellants’ contention that the combination of Logtenberg, Caplan, Colsky, Kim, and Thomas fails to suggest attaching a targeting moiety onto the surface of a cell to enhance adherence of the cell to tissue in which the cells are administered to, let alone linking a targeting moiety to a progenitor cell to target the progenitor cell to target tissue at a target tissue injury site and not adversely affect progenitor cell viability, mitotic potential, and phenotype (App. Br. 15; see also id. at 15—16 and 20-21; Reply Br. 2; cf. FF 1—16; see generally FF 14 (Colsky discloses “a method for incorporating palmitate- derivatized antibody molecules onto cell membranes where they function as [‘jsurrogate receptors’ (SR) for mediating specific cellular interactions” and, thereby, enable the palmitate-derivatized antibody molecules “to cooperate with endogenous target recognition structures in receptor-ligand interactions 10 Appeal 2015-003611 Application 10/550,590 at the cell-cell interface”); FF 15 (Kim discloses a broadly applicable “method [] in which palmitate-conjugated protein A (pal-protein A) incorporated onto cell membranes is used to anchor antibodies on the surface of cells,” wherein “cells can be coated with antibody (Ab) molecules of a desired specificity that can serve as artificial receptors for soluble or cell surface antigens (Ags)” (FF 15). As discussed above, the combination of Logtenberg, Caplan, Colsky, Kim, and Thomas suggests a composition, within the scope of Appellants’ claimed invention, comprising a progenitor cell and a targeting moiety, such as an antibody to type II collagen (FF 1—16). Therefore, we are not persuaded by Appellants’ contention that Thomas, alone, fails to “teach that antibodies to type II collagen can be linked to progenitor cells and once linked used to enhance adherence of the progenitor cell to a target tissue injury site (App. Br. 17; see generally Reply Br. 2) Appellants’ claimed invention does not require any particular percentage of targeting moiety modified precursor cells to survive implantation or be responsible for the formation of new tissue (see App. Br. 32) as long as some are effective to achieve tissue targeting. Therefore, we are not persuaded by Appellants’ reliance on Beauchamp’s disclosure of the percentage of unmodified muscle precursor cells that survive implantation and form new muscle (App. Br. 21—22; see Reply Br. 4—5). Further, for the reasons set forth above, we are not persuaded by Appellants’ contention that in view of Beauchamp and without the evidence provided by their Specification, “one having skill in th[is] art could not have found it predictable that attaching proteinaceous molecules to progenitor cells as recited in claim 1 would not adversely affect progenitor cell viability, 11 Appeal 2015-003611 Application 10/550,590 mitotic potential, and phenotype of the progenitor cells” (App. Br. 22; cf. FF 1-16; Ans. 4-6). For the foregoing reasons, we are not persuaded by Appellants’ contention that the rejection on this record: fails to provide “anyone having skill in the relevant art [with] a reasonable expectation of success,” “is too general and lacking in the type of particularity that is required to make out a prima facie case of obviousness,” is conclusory, and based in hindsight (App. Br. 24—27; see Reply Br. 2). “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). Further, notwithstanding Appellants’ contention to the contrary: “[A]ny need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed.” KSR, 550 U.S. at 420. Therefore, notwithstanding Appellants’ contention to the contrary, Examiner established an evidentiary basis on this record to support a conclusion that the combination of Logtenberg, Caplan, Colsky, Kim, and Thomas suggests a composition comprising a progenitor cell and a targeting moiety, within the scope of Appellants’ claimed invention and a reason for making such a composition (FF 1—16; see Ans. 4—6). CONCLUSION OF LAW The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness. The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable over the combination of Logtenberg, Caplan, Colsky, Kim, Thomas, and Simmons is affirmed. Claims 2, 4, 6, 8, 9, 11, 12 Appeal 2015-003611 Application 10/550,590 13-15, 26, 29, 39, 41, 45, 47, 48, 50, 52, 54—56, 67, 70, 80, 82, 85, 190, and 191 are not separately argued and fall with claim 1. 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. § 1.136(a). AFFIRMED 13 Copy with citationCopy as parenthetical citation