12808504 (P.T.A.B. Oct. 29, 2018)

Ex Parte Kubo et al

Patent Trial and Appeal BoardOct 29, 2018

12808504 (P.T.A.B. Oct. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/808,504 08/27/2010 27885 7590 FAY SHARPE LLP 1228 Euclid Avenue, 5th Floor The Halle Building Cleveland, OH 44115 10/30/2018 FIRST NAMED INVENTOR Takanori Kubo 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. 9237-98172 3931 EXAMINER GALISTEO GONZALE, ANTONIO ART UNIT PAPER NUMBER 1636 MAIL DATE DELIVERY MODE 10/30/2018 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 TAKANORI KUBO, HIDEKI OHBA, KAZUO SAKURAI, JUSAKU MINARI, and ATSUSHI UN0 1 Appeal2017-009475 Application 12/808,504 Technology Center 1600 Before DEMETRA J. MILLS, ULRIKE W. JENKS, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision under 35 U.S.C. Â§ 134(a) involving claims directed to a method of inhibiting expression of a target gene in a cell. Claims 13 and 15-23 are on appeal as rejected under 35 U.S.C. Â§ 103. We have jurisdiction under 35 U.S.C. Â§ 6(b ). We affirm. 1 Appellants identify the Real Party in Interest as "Napa Jenomics Co., Ltd." Appeal Br. 1. Herein we reference the Specification of June 16, 2010 ("Spec."); Final Office Action of May 13, 2016 ("Final Action"); Appeal Brief of Nov. 4, 2016 ("Appeal Br."); Examiner's Answer of May 2, 2017 ("Answer"); and Reply Brief of June 30, 2017 ("Reply Br."). Appeal2017-009475 Application 12/808,504 STATEMENT OF THE CASE Independent claim 13 is representative and is reproduced below: 13. A method of inhibiting expression of a target gene in a cell, comprising: a step of introducing a polysaccharide having a /J-1,3- glucan skeleton/double-stranded RNA complex into a cell; wherein said polysaccharide is schizophyllan; wherein the polysaccharide/double-stranded RNA complex contains double-stranded RNA having a sense strand RNA consisting of a base sequence complementary to a target sequence in a target gene and an antisense strand RNA containing a base sequence complementary to the sense strand RNA, and capable of inhibiting expression of the target gene; the double-stranded RNA has a single-stranded polydeoxyadenine bound directly or via a linker to at least one end of the sense strand and antisense strand; and the polysaccharide and the single-stranded polydeoxyadenine form a complex. Appeal Br. 20 (Claims Appendix). The following rejections are appealed: Claims 13, 15, and 19--23 stand rejected under 35 U.S.C. Â§ 103(a) over Shinkai '612, 2 Han, 3 and Shinkai '913. 4 Final Action 3. 2 JP 2005-204612 A (published Aug. 4, 2004) (English translation) ("Shinkai '612). 3 Xuelin Han et al., /J-1,3-Glucan-lnduced Host Phospholipase D Activation Is Involved in Aspergillus fumigatus Internalization into Type II Human Pneumocyte A549 Cells, 6(7) PLoS ONE 1-12 (2011) ("Han"). 4 JP 2006-069913 A (published Mar. 16, 2006) (English translation) ("Shinkai '913"). 2 Appeal2017-009475 Application 12/808,504 Claims 13 and 15-23 stand rejected under 35 U.S.C. Â§ 103(a) over Shinkai '612, Han, Shinkai '913, and Caplen. 5 Id. at 10. FINDINGS OF FACT ("FF") We adopt the Examiner's findings of fact and rationale as set forth in the Final Action and Answer. The following findings of fact highlight certain evidence. FF 1. Shinkai '612 discloses a method for "transferring double- stranded DNA into a cell, having high transfection efficiency" by "tail-bonding DNA" (via poly(dA) [polydeoxyadenine] tail) to form a "complex[] with a P-1,3-glucan polysaccharide ( e.g., sizofiran [aka, schizophyllan ])," which is "transferred to a target call as a nucleic acid-polysaccharide complex." Shinkai '612 Abstract; see also id. ,r,r 16-18, 20, 22-25, 42. FF2. Further to the preceding finding of fact, Shinkai '612 discloses that the "beta-1,3-glucan system polysaccharide will be used as a gene carrier" for the purpose of facilitating passage of the nucleotide past the cell membrane. Shinkai '612 ,r,r 22-25. FF3. Shinkai '913, similar to Shinkai '612, discloses complexing a functionalized P-1,3-glucan ( e.g., sizofiran, e.g., combined with polyethylene glycol) with a double-stranded nucleotide (e.g., siRNA, with sense and antisense strands), via dA at 3' terminal, to improve transfection into a target cell. Shinkai '913 Abstract, claims 1, 10, 11, ,r,r 3, 17, 23, 24, 29, 47, 51. 5 Natasha J. Caplen et al., Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems, 98(17) PNAS 9742--47 (2001) ("Caplen"). 3 Appeal2017-009475 Application 12/808,504 FF4. Further to the preceding finding of fact, Shinkai '913 suggests that, as /J-1,3-glucan complexing agents, siRNA and DNA are interchangeable alternatives. Shinkai '913 ,r 29, claim 10. FF5. Each of Shinkai '612 and Shinkai '913 discloses that /J-1,3-glucan's use in clinical medicine has been known for many years and its safety confirmed, as well as the fact that /J-1,3 glucan was known to be used as a gene carrier. Shinkai '612 ,r,r 6-8; Shinkai '913 ,r,r 7-9. FF6. Further to the preceding findings of fact, based on the teachings of Shinkai '612 and Shinkai '913, and as determined by the Examiner, it would have been obvious to a person of ordinary skill in the art at the time of the invention to have the nucleotide/beta-1,3- glucan complex described by Shinkai '612 and use a siRNA molecule as the nucleotide as described by Shinkai '913 because siRNA is specially suitable for these complex and using an siRNA molecule instead of DNA encoding an siRNA would eliminate the need for the DNA to be transcribed, which would eliminate variations in transcription, and therefore, siRNA levels. Furthermore, since both Shinkai '612 and Shinkai '913 are directed to double stranded nucleotide/beta-1,3-glucan complexes for transfection, it would have been obvious to a person of ordinary skill to use siRNA instead of double stranded DNA as the nucleotide in the complex with the predictable result of creating a complex suitable for transfection. Given the teachings of the prior art and the level of the ordinary skilled artisan at the time of the applicant's invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention. See Final Action 6-7; see also Shinkai '612 ,r,r 26-43 and Shinkai '913 ,r,r 47-57 (examples) (evidencing success of each individual 4 Appeal2017-009475 Application 12/808,504 reference's methods in complexing /J-1,3-glucan with nucleotides for cell transfection). FF7. Han provides evidence that A549 cancer cells express dectin-1, which is a /J-1,3-glucan receptor. Han 1 (Abstract). FF8. Caplen discloses that "[s]hort interfering RNAs (siRNAs) are double-stranded RN As of -21-25 nucleotides that have been shown to function as key intermediaries in triggering sequence- specific RNA degradation during posttranscriptional gene silencing in plants and RNA interference in invertebrates" and "siRNAs can induce gene-specific inhibition of expression." Caplen 9742. FF9. Caplen discloses that "siRNAs seem to avoid the well documented nonspecific effects triggered by longer double-stranded RNAs in mammalian cells." Caplen 9742. DISCUSSION "[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting aprimafacie case ofunpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). Arguments made by Appellants in the Appeal Brief and properly presented in the Reply Brief have been considered in this Decision; arguments not so- presented in the Briefs are waived. See 37 C.F.R. Â§ 4I.37(c)(l)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) ("Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived."). "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." 5 Appeal2017-009475 Application 12/808,504 KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid underÂ§ 103." Id. at 419. The Examiner determined claims 13, 15, and 19--23 would have been obvious over the combination of Shinkai '612, Han, and Shinkai '913, and further determined that all claims would have been obvious over this same prior art combination when also adding Caplen. Final Action 3-11 and Answer 2-16 (collectively citing Shinkai '612 ,r,r 16-18, 20, 22-25, 42, 43; Shinkai '913 claims 1, 10, ,r,r 23, 24, 29, 47, 51; Han Abstract; Caplen 9743, 97 46); see also FF 1-FF9. We discern no error in the Examiner's determinations. We adopt the Examiner's findings of fact and rationale in this Decision. See Final Action 3-11; Answer 2-16. Appellants present several arguments. Appellants' arguments respective of each obviousness rejection are substantially the same and we address both rejections together. Moreover, because the second obviousness rejection including the Caplan reference in combination with the Shinkai references and Han is directed to all claims, it subsumes the first rejection. Appellants argue Han is not prior art and, therefore, improperly cited in rejecting the claims. Appeal Br. 8. This argument is not persuasive because, as indicated by the Examiner, Han's teachings are not essential for the Examiner's prima facie case for obviousness. Answer 3. Han's teachings evidence that A549 cells express dectrin-1, which is a /J-1,3- glucan receptor. See FF7; see also Answer 3. A549 cells are a type of cells 6 Appeal2017-009475 Application 12/808,504 disclosed by Shinkai '612 to have been successfully transfected with its disclosed P-1,3-glucan (sizofiran)-DNA complex; Han provides a scientific explanation for this effective transfection. Shinkai '612 ,r 42. Appellants argue the combination of Shinkai '612 and Shinkai '913 does "not suggest introducing a polysaccharide having a P-1,3-glucan skeleton/double-stranded RNA complex into a cell." Appeal Br. 9. Appellants' argument relies largely on the contention that Shinkai '612 discloses complexing the preferred saccharide with DNA, rather than RNA, and that Shinkai '913 is for some reason limited to single-stranded RNA complexes. Id. at 9 and 10. Appellants also cite two declarations6 as evidence that Shinkai '612 's disclosure is so-limited and also that there are some distinctions between cellular reactions to dsRNA and single stranded RNA, the former being recognized by Dicer and cut into siRNA. These arguments and evidence are not persuasive. It is the combination of Shinkai '612 and Shinkai '913 that renders claim 13 obvious, not either reference alone, and arguments attacking combined prior art references individually are not persuasive. See In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Shinkai '612 teaches that double stranded nucleotides, i.e., DNA, can be effectively transfected into cells by complexing them withfi-1,3-glucan. FF1-FF2, FF5-FF6. Shinkai '913 teaches that this same saccharide can be complexed with other double stranded nucleotides for the same purpose. FF3-FF6; see also Shinkai '913 6 Kumiko Ui-Tei Declaration Under 37 C.F.R. Â§ 1.132, dated Dec. 17, 2012 ("Ui-Tei Declaration"); Seiji Shinkai Declaration Under 37 C.F.R. Â§ 1.132, dated Jan. 27, 2015 ("Shinkai Declaration"). 7 Appeal2017-009475 Application 12/808,504 ,r 29 ("2 chain nucleic acid, plasmid DNA, etc. are included as nucleic acid used by this invention, especially suitable nucleic acid substances are oligonucleotides, such as an antisense DNA, siRNA, and CpG DNA, from a practical viewpoint."). Moreover, Shinkai '913 's disclosed siRNAs, which are complexed with /J-1,3-glucan and transfected into cells, are double- stranded RNA molecules. See, e.g., FF8; see also Nature.com, siRNAs, https://www.nature.com/subjects/simas, Oct. 23, 2018. Because they are directed to the same goals and use either the same and/or similar complexing components, it would have been obvious to substitute the double-stranded RNA molecules of Shinkai '913 into the /J-1,3-glucan complex of Shinkai '612 to replace DNA (or, even considering Shinkai '913 individually, the reference discloses complexing siRNA, a double-stranded nucleotide molecule, with /J-1,3-glucan for cellular transfection). FF1-FF6. Appellants argue there would have been no reason to combine different embodiments of Shinkai '913, one "with a double-stranded siRNA having a single-stranded polydeoxyadenine bound directly of via a linker to at least one end of the sense strand and antisense strand, and a beta-1,3- glucan." Appeal Br. 13. This argument is not persuasive. As indicated above, Shinkai '913 explicitly suggests complexing /J-1,3-glucan with siRNA and, moreover, substituting Shinkai '913's siRNA for Shinkai '612's DNA in the latter's /J-1,3-glucan complex would have been an obvious substitution based on the disclosures of each reference. See FF1-FF6. Appellants argue the Examiner has not provided adequate rationale for combining Shinkai '612 and Shinkai '913. Appeal Br. 13. This is not a persuasive argument. As discussed above, the Examiner determined it 8 Appeal2017-009475 Application 12/808,504 would have been obvious to combine these references because they are directed to the same goal of transfecting nucleotides into cells by complexing withfi-1,3-glucan. The references suggest Shinkai '612's DNA and Shinkai '913 's double-stranded RNA are interchangeable for this purpose. FF6. Moreover, the Caplan reference provides additional motivation to use Shinkai '913 's siRNA in a saccharide complex as disclosed by Shinkai '612, because of the advantages in gene silencing and inhibition and the avoidance of adverse effects when using siRNA. See FF8-FF9. Appellants also argue "[t]here would have been no reasonable expectation that the combination of Shinkai '913 and Shinkai '612 would [have been] successful." Appeal Br. 14. This argument is not persuasive. As discussed above, both Shinkai '612 and Shinkai '913 teach successfully transfecting cells with nucleotides by complexing them with P-1,3-glucan (and potentially functional groups). FF1-FF6. Furthermore, Caplen discloses that siRNAs, as disclosed by Shinkai '913, were known to be effective gene-inhibitors. FF8. For the reasons above, we conclude the Examiner has established a prima facie case that claim 13 would have been obvious over the cited prior art combination( s ), which has not been shown to be error by Appellants. As they were argued as a group by Appellants and we find independent claim 13 to be representative, all claims fall with claim 13. 9 Appeal2017-009475 Application 12/808,504 SUMMARY The obviousness rejections under 35 U.S.C. Â§ 103 are each affirmed. 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. Â§ 1.136(a)(l )(iv). AFFIRMED 10