Ex Parte Schwabe et alDownload PDFPatent Trial and Appeal BoardMay 24, 201612257146 (P.T.A.B. May. 24, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/257,146 10/23/2008 72932 7590 05/25/2016 Steinfl & Bnmo LLP 155 N. Lake Ave. Ste 700 Pasadena, CA 91101 FIRST NAMED INVENTOR Nikolai Franz Gregor Schwabe 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. P862-US 6498 EXAMINER DIBRINO, MARIANNE ART UNIT PAPER NUMBER 1644 MAILDATE DELIVERY MODE 05/25/2016 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 NIKOLAI FRANZ GREGOR SCHWABE, LINDA CHENG-CHOO TAN, CATHERINE ELIZABETH NAPPER, JEREMY WILLIAM FRY, SUSAN PANG, and RACHEL KATE SPOONER1 Appeal 2014-001190 Application 12/257,146 Technology Center 1600 Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and RICHARD J. SMITH, Administrative Patent Judges. SMITH, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to an oligomeric major histocompatibility complex (MHC). We have jurisdiction under 35 U.S.C. § 6(b ). We affirm. 1 According to Appellants, the real party in interest is Proimmune, LLC. (Appeal Br. 2.) Appeal 2014-001190 Application 12/257,146 STATEMENT OF THE CASE Background [I]solated or recombinant forms of MHC-peptide molecules are useful for detecting, separating and manipulating T cells according to the specific peptide antigens these T cells recognize . . . the interaction between MHC molecules and [T cell receptors] across cell surfaces is multimeric in nature and [] the affinity of a single MHC molecule for a given [T cell receptor] is generally low in affinity. As a consequence, there has been an effort to develop multimeric forms of isolated or recombinant MHC-peptide molecules to make such molecules more useful. (Spec. ,-i,-i 4-5.) Claims on Appeal Claims 1-17, 20, 24, and 25 are on appeal. (Claims Appendix, Br. 87-90.) Independent claim 1 is illustrative and reads as follows: 1. An oligomeric MHC complex comprising at least three chimeric proteins, said chimeric proteins comprising a first section derived from an MHC peptide chain or a functional part thereof and a second section comprising an oligomerising domain derived from an oligomer-forming coiled-coil protein, wherein formation of the oligomeric MHC complex occurs by oligomerisation at the oligomerising domain of the chimeric proteins, and wherein at least two of the first sections are derived from the same MHC peptide chain. (Id. at 87.) Examiner's Rejections 1. Claims 4 and 14 stand rejected under 35 U.S.C. § 112, second paragraph, as indefinite. (Ans. 4-5.) 2. Claims 1-3, 6-13, and 20 stand rejected under 35 U.S.C. § 103(a) as 2 Appeal 2014-001190 Application 12/257,146 unpatentable over Rhode,2 Terskikh '943,3 Terskikh,4 Muller, 5 Efimov '94,6 and Efimov '96. 7 (Id. at 5-11.) 3. Claims 4, 5, 14-17, 24, and 25 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Rhode, Terskikh '943, Terskikh, Muller, Efimov '94, Efimov '96, Dinser,8 and Newton. 9 (Id. at 11-14.) The Examiner also entered provisional rejections, on the ground of nonstatutory obviousness-type double patenting, of ( 1) claims 1-3, 6-13, and 20 over claims 1-23, 29, 35, and 36 of Application No. 10/770,140, and (2) claims 4, 5, 14-17, 24, and 25 over claims 1-23, 29, 35, and 36 of Application No. 10/770,140 in view ofDinser and Newton as evidenced by admissions in the Specification. (Final Act. 12.)10 The Examiner also provisionally rejected claims 1-17, 20, 24, and 25 as being drawn to an 2 Rhode et al., WO 99/21572 Al, published May 6, 1999 ("Rhode"). 3 Terskikh et al., WO 98/18943 Al, published May 7, 1998 ("Terskikh '0Ll1"\ ./-0--1 }· 4 Terskikh et al., "Peptabody ":A new type of high avidity binding protein, PROC. NATL. ACAD. SCI. USA 94, 1663-68 (Mar. 1997) ("Terskikh"). 5 Muller et al., Protein Fusions to Coiled-Coil Domains, METHODS IN ENZYMOLOGY 328, 261-82 (2000) ("Muller"). 6 Efimov et al., The thrombospondin-like chains of cartilage oligomeric matrix protein are assembled by a five-stranded a-helical bundle between residues 20 and 83, FEBS LETTERS 341, 54-58 (1994) ("Efimov '94"). 7 Efimov et al., Crystallization and Preliminary Crystallographic Study of the Pentamerizing Domain From Cartilage Oligomeric Matrix Protein: A Five-Stranded a-Helical Bundle, PROTEINS: STRUCTURE, FUNCTION, AND GENETICS 24, 259-62 (1996) ("Efimov '96"). 8 Dinser et al., Pseudoachondroplasia is caused through both intra- and extracellular pathogenic pathways, 110 THE JOURNAL OF CLINICAL INVESTIGATION 4, 505-13 (2002) ("Dinser"). 9 Newton et al., Characterization of Human and Mouse Cartilage Oligomeric Matrix Protein, GENOMICS 24, 435-39 (1994) ("Newton"). 10 Office Action dated July 2, 2012. 3 Appeal 2014-001190 Application 12/257,146 invention not patentably distinct from claims 1-23, 29, 35, and 36 of commonly assigned Application No. 10/770,140. (Id. at 14.) However, because USPTO records indicate that Application No. 10/770,140 is abandoned, these provisional rejections are moot. 11 FINDINGS OF FACT We adopt as our own the Examiner's findings and analysis concerning the scope and content of the prior art. The following findings are included for emphasis and reference convenience. FF 1. The Examiner finds that Rhode teaches oligomeric MHC single chain (sc) class I or class II complexes comprising a first portion, consisting of one or more single chain class I or class II molecules, linked or fused to a joining molecule, "said joining molecule linking the first portion to a second portion" (e.g. Formula I at Rhode 30.). (Final Act. 4.) FF 2. The Examiner finds that the MHC complex of Rhode can optionally include an effector molecule that can be an scFV antibody, and that the joining molecule can be a coiled-coil domain. (Id.) FF 3. The Examiner finds that Rhode teaches the advantages of using an MHC oligomeric complex containing coiled-coil domains to increase avidity of MHC complexes. (Id. at 6.) FF 4. The Examiner finds that Terskikh '943 "teaches that small peptides can be pentamerized using the pentamerization domain of COMP 12 (a coiled-coil)." (Id. at 4.) 11 Notice of Abandonment mailed Apr. 13, 2015. 12 COMP stands for "cartilage oligomeric matrix protein." (See Terskikh '943 3, 1. 1 and Appeal Br. 87, claim 4.) 4 Appeal 2014-001190 Application 12/257,146 FF 5. In reference to the COMP assembly domain, Terskikh '943 teaches that "oligomerization of short peptides bypass[ es] folding problems and overcomes expression difficulties previously experienced during oligomerization of relatively complex proteins such as single chain Fv fragments." (T erskikh '94 3 5, 11. 15-1 7.) FF 6. The Examiner finds that Terskikh teaches "a pentameric peptabody comprising the pentamerization domain of COMP, a coiled-coil assembly domain." (Final Act. 5.) FF 7. T erskikh teaches that the COMP assembly domain ... spontaneously forms a five- stranded a-helical bundle, the highest oligomerization state known for a compact coiled-coil structure ... [t]hese properties, taken together with a remarkable solubility in salt-free water ... and thermostability, make the COMP assembly domain an ideal pentamerization tool for protein engineering ... the display of short peptides in a pentameric form on [peptabody] molecules bypasses the folding problems and the difficulties previously encountered during the expression of oligomeric forms of relatively complex proteins, such as single-chain Fv fragments. (Terskikh 1668, left col.) FF 8. The Examiner finds that Muller teaches that "chimeric multimers made by genetic fusions to heterologous oligomerization domains can be constructed with coiled coils that act as versatile fusion partners" and the use of "coiled coils to generate chimeric proteins with higher avidity." (Final Act. 5.) FF 9. The Examiner finds that Muller teaches "the versatility and stability of coiled-coil domains for oligomerizing proteins, the advantage of increased 5 Appeal 2014-001190 Application 12/257,146 avidity that their use provides, and their use in various diagnostic and therapeutic applications." (Id. at 6.) FF 10. The Examiner finds that Efimov '94 teaches that "amino acid residues 20-83 of COMP protein can be easily expressed and purified." (Id.) FF 11. The Examiner finds that Efimov '96 teaches "the location of the COMP coiled-coil assembly domain and that this domain spontaneously forms a pentameric structure." (Id.) DISCUSSION Issue No. 1 Whether a preponderance of evidence of record supports the Examiner's conclusion that claims 4 and 14 are indefinite under 35 U.S.C. § 112, second paragraph. Analysis The Examiner found that claims 4 and 14 were indefinite because of a lack of clarity regarding their recitation of the "oligomerising domain" being "derived from the pentamerisation domain of the human cartilage oligomeric matrix protein (COMP)." (Ans. 4-5.) In particular, the Examiner found that it was not clear which "range of amino acid residues" corresponds to the pentamerisation domain and which corresponds to the oligomerizing domain. (Id. at 4.) However, the Examiner also found that Efimov '94 teaches that "amino acid residues 20-83 of COMP protein can be easily expressed and purified" (FF 10) and that Efimov '96 teaches the location of 6 Appeal 2014-001190 Application 12/257,146 the COMP domain and that it "spontaneously forms a pentameric structure" (FF 11 ). (Final Act. 6.) Appellants respond by stating that the recitation in paragraph 95 of the Specification regarding SEQ ID N0:23, namely, "a region encoding the coiled-coil domain (amino acids 21-85)," is an example of an "oligomerising domain" derived from "human COMP." (Appeal Br. 17.) As further explained by Appellants, that sequence completely or substantially overlaps with the pentamerisation domain of COMP described in the Specification as "amino acids 1 to 128, preferably 20 to 83, most preferably 20 to 72 of said protein." (Id.; Spec. ,-i 22.) We are persuaded by Appellants' argument. We find that a person of ordinary skill in the art, after considering the Specification, the teachings of the prior art, and putting the disputed phrase in context, would find that the recitation of the "oligomerising domain" of a chimeric protein being "derived from the pentamerisation domain of the human cartilage oligomeric matrix protein (COMP)" is sufficiently clear. See In re Packard, 751 F.3d 1307, 1313 (Fed. Cir. 2014) ("[H]ow much clarity is required necessarily invokes some standard of reasonable precision in the use of language in the context of the circumstances."). Accordingly, we reverse the Examiner's rejection under 35 U.S.C. § 112, second paragraph. Conclusion A preponderance of evidence of record fails to support the Examiner's conclusion that claims 4 and 14 are indefinite under 35 U.S.C. § 112, second paragraph. 7 Appeal 2014-001190 Application 12/257,146 Issue No. 2 Whether a preponderance of evidence of record supports the Examiner's conclusion of obviousness as to claims 1-3, 6-13, and 20. Analysis The Examiner concluded that it would have been prima facie obvious to have used the coiled-coil COMP assembly domain, as taught by Terskikh '943, Terskikh, Muller, Efimov '94, and Efimov '96, as the coiled-coil domain in the MHC oligomeric construct (Formula I) taught by Rhode. (Final Act. 6.) The Examiner further concluded that it would have been prima facie obvious to have made the Rhode construct without the scFv antibody since Rhode teaches that the scFv effector molecule is optional. (Id.) Furthermore, the Examiner concluded that one of ordinary skill in the art would have been motivated to prepare an MHC complex as claimed, in order to create a higher avidity MHC multimer, because of the advantageous properties of coiled-coil domains (e.g. COMP). (Id.; see FF 3, 7, and 9-11.) We find that the Examiner has satisfied the burden of showing "some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Moreover, the Examiner has established a prima facie case of obviousness and, as discussed below, Appellants have not overcome that prima facie case. Claim 1 As an initial matter, Appellants focus on the cited references separately, and their alleged individual deficiencies. However, Appellants are reminded that one cannot show nonobviousness by attacking references individually where the Examiner bases the rejection on a combination of 8 Appeal 2014-001190 Application 12/257,146 references. Jn re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (citing In re Keller, 642 F.2d 413, 425 (CCPA 1981)). Moreover, a prior art reference may be read for all that it teaches, including uses beyond its primary purpose. In re Mouttet, 686 F.3d 1322, 1331 (Fed. Cir. 2012). Formula I of Rhode Appellants argue that "in view of the number of substituents recited in Formula I of [Rhode] ... the selection at issue would encompass quite a large number of substituents." (Appeal Br. 41.) Furthermore, Appellants argue that "[Rhode] relates to a general formula encompassing a very large [number] of compounds with express indications leading towards 'bispecific complex' in which the joining molecules of choice are 'Immunoglobulin Joining Molecules."' (Id. at 42.) We are not persuaded. While we acknowledge that the MHC complex of Rhode (Formula I) discloses a number of possible formulations or combinations, Rhode expressly recites "one or more sc-MHC" molecules and "chimeric polyspecific MHC complexes" that can include a "coiled-coil protein" as a joining molecule. (Rhode 30, 1. 4-32, 1. 4.) Furthermore, Appellants' claim 1 recites "[a]n oligomeric MHC complex comprising at least three chimeric proteins, said chimeric proteins comprising a first section derived from an MHC peptide chain or a functional part thereof and a second section comprising an oligomerising domain derived from an oligomer-forming coiled-coil protein," and is otherwise not limited to particular substituents. (Appeal Br. 87.) In addition, while some selection from Rhode may be required to arrive at claim 1, "picking and choosing may be entirely proper in the making of a 103, obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972). In this case, the recitation of claim 9 Appeal 2014-001190 Application 12/257,146 1, in view of the teachings of Rhode in combination with the other cited references, does not persuade us that any requirement for such a selection would render claim 1 nonobvious. Moreover, in an obviousness rejection, the mere fact that a reference discloses different combinations does not render any particular combination less obvious. See Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) ("That the [prior art] patent discloses a multitude of effective combinations does not render any particular formulation less obvious"). We are similarly unpersuaded by Appellants' argument regarding the "bispecific" nature of Rhode' s MHC complexes, with "Immunoglobulin Joining Molecules." (Appeal Br. 42.) First, Rhode teaches that"[ e ]xamples of other suitable joining molecules include ... coiled-coil protein binding motifs" and its teaching is not limited to Immunoglobulin Joining Molecules. Second, Appellants' focus on "bispecific" complexes, i.e., that Rhode does not expressly teach at least three chimeric proteins, ignores the teachings of other references combined with Rhodes that clearly teach pentameric complexes. (See, e.g., FF 4, 7.) Use of Coiled-Coil Proteins Appellants argue that "a skilled person would not use coiled coil proteins as [] 'joining molecules' beyond their use disclosed in [Rhode]" to multimerise the MHC molecules as recited in claim 1. (Appeal Br. 44; Reply Br. 4.) In support of that argument, Appellants point to the phrase "folding problems and difficulties" in Terskikh, and further rely on the Nepom Declaration13 which Appellants contend "evidences that a skilled 13 Rule 1.132 Declaration of Gerald T. Nepom, dated July 4, 2007 ("Nepom Declaration"). 10 Appeal 2014-001190 Application 12/257,146 person would not use coiled coil proteins as a scaffold to multimerise MHC molecules." (Appeal Br. 47.) We are not persuaded by Appellants' arguments. Terskikh teaches that usage of the COMP assembly domain "bypasses the folding problems and the difficulties previously encountered during the expression of oligomeric forms of relatively complex proteins, such as single-chain Fv fragments." (emphasis added) (Terskikh 1668, left col.; FF 7.) Thus, rather than leading a skilled person away from using coiled coil proteins, Terskikh actually encourages such usage. 14 We are similarly unpersuaded by Appellants' reliance on the N epom Declaration. The Nepom Declaration states that Terskikh would have been viewed by one of ordinary skill in the art "as discouraging the use of a coiled-coil protein like that of the present invention for MHC multimers." (Nepom Deel. ,-i 4.) However, for the reasons stated above regarding the teachings of Terskikh, we are not persuaded by this statement. The Nepom Declaration also states that "the [immunoglobulin] variable domains are structurally similar in size and orientation to the MHC domains which are used in the multimers," but nevertheless concludes that "the change in scaffold to the coiled-coil protein would not" have been considered readily apparent to a person of ordinary skill in the art. (Nepom Deel. ,-i 5.) However, we find this conclusion upersuasive in view of the acknowledged structural similarity and the teachings of the prior art, such as Terskikh. 14 We also acknowledge Appellants' argument that the "difficulties" referenced by Terskikh would change the principle of operation of Rhode, or defeat the intended purpose of the joining molecules of Rhode. (Appeal Br. 52; Reply Br. 4.) We are not persuaded by this argument in view of the actual teachings of Terskikh. 11 Appeal 2014-001190 Application 12/257,146 The Nepom Declaration further states that, due to "a large number of biochemical and structural reasons ... [t]here simply was no way, a priori, to predict that these significant issues would actually be able to accommodate the MHC peptide structure as ligand attached to a portion of the coiled-coil protein." (Nepom Deel. ,-i 6.) We are not persuaded by this statement because a conclusion of obviousness requires a reasonable expectation of success, not absolute predictability. See In re 0 'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). Teaching Away Appellants argue that Terskikh, Muller, and Terskikh '943 teach against the use of coiled-coil proteins for MHC multimers. (Appeal Br. 44- 59.) We are not persuaded. None of the cited references "teach away" because they do not criticize, discredit, or otherwise discourage the claimed invention. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). To the contrary, as explained by the Examiner and discussed herein, the references teach and suggest the claimed invention. Moreover, Appellants improperly focus on isolated portions of the references rather than considering the entirety of their teaching. See In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). Hindsight Appellants argue that the Examiner has engaged in improper hindsight. (See, e.g., Appeal Br. 37, 44.) However, we find Appellants' argument that the Examiner engaged in hindsight to be unpersuasive. Rather than using hindsight, the Exam in er points to specific disclosures in the prior art that describe the limitations ofAppellants' claimed invention. (Final Act 4----9.) \Ve therefore find that the Examiner's obviousness conclusion is 12 Appeal 2014-001190 Application 12/257,146 based on sufficiently articulated reasoning that overcomes any concen1s about hindsight bias. See KSR, 550 U.S. at 418. Claim 13 Appellants state that "the same remarks presented ... with reference to claim 1 apply with respect to the obviousness allegation of instant claim 13." (Appeal Br. 78.) Accordingly, the rejection of claim 13 is affirmed for the reasons stated above in connection with claim 1. Claims 2, 3, 6-12, and 20 Appellants note the dependency of these claims on claim 1 and present no additional arguments with respect to the rejection of claims 2, 3, 6-12, and 20. (Appeal Br. 77.) Accordingly, we affirm the rejection of these claims as well. See Hyatt v. Dudas, 551F.3d1307, 1314 (Fed. Cir. 2008). Conclusion of Law A preponderance of evidence of record supports the Examiner's conclusion of obviousness as to claims 1-3, 6-13, and 20. Issue No. 3 Whether a preponderance of evidence of record supports the Examiner's conclusion of obviousness as to claims 4, 5, 14-17, 24, and 25. Analysis The Examiner concluded that claims 4, 5, 14-17, 24, and 25 would have been obvious based on the references as applied in connection with the rejection of claims 1 and 13 above, and further in view of Dinser's teaching regarding human COMP, including that its sequence was known, and Newton's teaching regarding cloning and sequencing of human COMP and the region that is required for pentamer formation. (Final Act. 10.) 13 Appeal 2014-001190 Application 12/257,146 Accordingly, we find that the Examiner has satisfied the burden of showing "some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." KSR, 550 U.S. at 418. Claims 4, 5, and 14-17 Appellants recite the language of claims 4, 5, and 14-1 7, and state that claims 4 and 5 depend on claim 1 and that claims 14-1 7 depend on claim 13. (Appeal Br. 81-84.) Furthermore, Appellants state that "the same remarks presented in connection with the rejection of claims 1-3, 6-13, and 20 ... also apply here" and that "the same conclusions and rationale also applies to the alleged further combination ... with Dinser and [Newton]." (Id. at 83-84.) We affirm the rejection of claims 4, 5, and 14-1 7 for the same reasons stated above in connection with claims 1 and 13, and Appellants' failure to provide a substantive argument in response to the rejection. See 37 C.F.R. § 41.37(c)(l)(iv) ("A statement which merely points out what a claim recites will not be considered an argument for separate patentability of the claim."); see also In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011) ("[W]e hold that the Board reasonably interpreted Rule 41.37 to require more substantive arguments in an appeal brief than a mere recitation of the claim elements and a naked assertion that the corresponding elements were not found in the prior art."). Claims 24 and 25 Appellants note the dependency of claims 24 and 25 on claim 4 and present no additional arguments with respect to the rejection of claims 24 and 25. (Appeal Br. 84.) Accordingly, we affirm the rejection of claims 24 and 25 as well. See Hyatt, 551 F.3d at 1314. 14 Appeal 2014-001190 Application 12/257,146 Conclusion ofLaw A preponderance of evidence of record supports the Examiner's conclusion of obviousness as to claims 4, 5, 14-17, 24, and 25. SUMMARY We reverse the rejection of claims 4 and 14 under 35 U.S.C. § 112, second paragraph. We affirm the rejection of claims 1-3, 6-13, and 20 under 35 U.S.C. § 103(a). We affirm the rejection of claims 4, 5, 14-17, 24, and 25 under 35 U.S.C. § 103(a). 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. § l.136(a). AFFIRMED 15 Copy with citationCopy as parenthetical citation