Ex Parte Tohata et alDownload PDFPatent Trial and Appeal BoardSep 19, 201310578613 (P.T.A.B. Sep. 19, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte MASATOSHI TOHATA, KAZUHISA SAWADA, KATSUYA OZAKI, KAZUO KOBAYASHI, and NAOTAKE OGASAWARA ____________ Appeal 2011-012756 Application 10/578,613 Technology Center 1600 ____________ Before DONALD E. ADAMS, ERIC GRIMES, and JOHN G. NEW, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL1 This appeal under 35 U.S.C. § 134 involves claims 1-15 (App. Br. 4). Examiner entered rejections under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 The Real Party in Interest is Kao Corporation (App. Br. 2). Appeal 2011-012756 Application 10/578,613 2 STATEMENT OF THE CASE The claims are directed to a recombinant microorganism and a method for producing a protein or polypeptide. Claim 1 is representative and is reproduced in the Claims Appendix of Appellants’ Brief. Claims 1-15 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Ferrari,2 Gardan,3 and Hakamada.4 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Ferrari suggests a recombinant microorganism, Bacillus subtilis, and method for producing a microorganism that has “been genetically manipulated to have an altered[, i.e., enhanced,] capacity to produce expressed [heterologous] proteins” (Ferrari, Abstract; id. at 1: 34-37; id. at 2: 24-34; Ans. 5). FF 2. Ferrari suggests a recombinant microorganism, Bacillus subtilis, and method for producing a microorganism wherein one or more chromosomal genes selected from the group consisting of, inter alia, rocA, rocF, and rocD have been inactivated (Ferrari 2: 24-34; Ans. 5). 2 Eugenio Ferrari, et al., WO 03/083125 A1, published October 9, 2003. 3 Rozenn Gardan, et al., Role of the transcriptional activator RocR in the arginine-degradation pathway of Bacillus subtilis, 24(4) MOLECULAR MICROBIOLOGY 825-837 (1997). 4 Yoshihiro Hakamada, et al., Deduced Amino Acid Sequence and Possible Catalytic Residues of a Thermostable, Alkaline Cellulase from an Alkaliphilic Bacillus Strain, 64(11) BIOSCI. BIOTECHNOL. BIOCHEM. 2281- 2289 (2000). Appeal 2011-012756 Application 10/578,613 3 FF 3. Examiner finds that Ferrari fails to suggest deleting, or inactivating, rocR or sigL (Ans. 6). FF 4. Gardan suggests that “[i]n Bacillus subtilis, genes involved in arginine and ornithine catabolism constitute two operons, rocABC and rocDEF” and that “[i]nducible expression of these two operons is SigL- dependent and requires the transcriptional activator RocR” (Gardan 825: col. 1, ll. 1-5; id. col. 2, ll. 6-18 (“The positive regulatory protein RocR is required for the expression of both [rocABC and rocDEF] operons”); see generally Ans. 6). FF 5. Examiner relies on Hakamada to suggest Appellants’ SEQ ID NO: 1, which is not suggested by the combination of Ferrari and Gardan (Ans. 6). ANALYSIS The claims were not separately argued and therefore stand or fall together. Claim 1 is representative. Based on the combination of Ferrari and Gardan, Examiner concludes that, at the time Appellants’ invention was made, it would have been prima facie obvious “to modify the Bacillus subtilis of Ferrari … by deleting rocR or sigL to achieve the predictable result of inactivating rocA, rocD and rocF and obtaining a microorganism suitable for protein production” (Ans. 6). We are not persuaded by Appellants’ contention that “it was far from predictable what the effects of knocking out rocR or sigL would have been” (App. Br. 10). To the contrary, the evidence of record suggests that a deletion of one or more genes from the roc operons results in enhanced expression of a heterologous protein (FF 1-2). The evidence of record further suggests that deletion of rocR or sigL will result in inactivation of both roc operons thereby achieving the same effect as independently Appeal 2011-012756 Application 10/578,613 4 deleting rocA, rocF, and rocD (FF 4; Ans. 7-8; Cf. FF 2). Therefore, we are not persuaded by Appellants’ contention that Examiner “failed to point out any teaching in the prior art suggesting that knocking out one of these genes would have been expected to increase protein synthesis by inactivating arginine catabolism pathways” (App. Br. 12-13 and 14; Cf. FF 1, 2, and 4). Notwithstanding Appellants’ contention to the contrary the rationale for deleting sigL or rocR is based on the combination of Ferrari and Gardan (FF 1-4). Therefore, we are not persuaded by Appellants’ contention that Examiner relied upon hindsight reasoning (App. Br. 11-12). For the foregoing reasons, as well as those expressed by Examiner, we are not persuaded by Appellants’ reliance on “[e]xpressio unius est exclusio alterius” (Reply Br. 3; see generally Ans. 5-24). Ferrari’s method of producing a microorganism comprises the deletion of one or more chromosomal genes selected from, inter alia, rocA, rocF, and rocD (FF 2). Therefore, notwithstanding Appellants’ contention to the contrary, Ferrari’s microorganism and method for producing the microorganism encompasses the inactivation of genes not specifically listed in Ferrari’s Markush grouping (see id.). Further, as Examiner explains, “knocking [out] one of rocR and sigL is not more complex than knocking out one of rocA, rocF, and rocD” (Ans. 9). Therefore, we are not persuaded by Appellants’ contention that it would have been “less complex” to “directly knock[] out the rocA, rocF, or rocD gene” (App. Br. 11). Gardan suggests that “[t]he positive regulatory protein RocR is required for the expression of both [rocABC and rocDEF] operons” (FF 4). Therefore, we are not persuaded by Appellants’ unsupported contention that Appeal 2011-012756 Application 10/578,613 5 “Examiner has not established that microbes do not express other activators of these operons or explained why knocking out only one of these protein activators would have been expected to substantially inactivate expression of these operons” (App. Br. 13). Ferrari suggests that deletion of one or more genes in the roc operons results in enhanced expression of a heterologous protein (FF 1-2). Therefore, we are not persuaded by Appellants’ unsupported contention that “Examiner has not established that the microbial cell lacked other redundant proteins for catabolizing arginine or that converting arginine into glutamine would have reduced heterologous protein synthesis” (App. Br. 14). We are not persuaded by Appellants’ intimation that reducing arginine transport into the cell will affect the amount of heterologous protein produced in a B. subtilis whose arginine catabolism pathway is blocked (App. Br. 15; see also App. Br. 17 (“one of ordinary skill in the art would have expected that knocking out rocR and sigL would have inhibited the expression of arginine permease and resulted in lower not higher cytoplasmic levels of arginine and lower levels of protein expression”); Reply Br. 3 (“Gardan as a whole teaches away from a reasonable expectation of success for increasing heterologous protein expression since the effects of deleting all the genes in these two operons … would have been unpredictable”); Cf. Ans. 20-21). The question is not whether “a cell where the arginine catabolism pathways are knocked out to boost the pool of arginine[] will produce a higher amount of a heterologous protein than a cell that contains these active pathways[, i.e., a wild-type cell],” but rather, whether Appellants have established an unexpected difference in the amount of heterologous protein Appeal 2011-012756 Application 10/578,613 6 produced from a microorganism that is commensurate in scope with their claim as compared to the closest prior art. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984). In this regard, we are not persuaded by Appellants’ contention that “there was no reasonable expectation of success for obtaining a microbial strain that expresses at least 200% more heterologous protein than an unmodified[, e.g., wild type,] strain” of B. subtilis (App. Br. 10-11; Reply Br. 2; see also App. Br. 17-18; Reply Br. 4; Spec. 26). Appellants’ evidence of unexpected results, as compared against a wild-type B. subtilis strain, fails to account for the closest prior art, i.e. Ferrari, which suggests that a microorganism comprising a deletion in one or more of the roc operon genes: rocA, rocF, and rocD will provide enhanced production of a heterologous protein (FF 2; see also Ans. 22). 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 Ferrari, Gardan, and Hakamada is affirmed. Claims 2-15 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 cdc Copy with citationCopy as parenthetical citation