Ex Parte Kay et al

Patent Trial and Appeal BoardMar 4, 2015

10259226 (P.T.A.B. Mar. 4, 2015)

UNITED STATES PATENT AND TRADEMARK OFFICE ____________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________________ Ex parte MARK A. KAY and ANTON MCCAFFREY ____________________ Appeal 2012-007597 Application 10/259,226 Technology Center 1600 ____________________ Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and SCOTT E. KAMHOLZ, Administrative Patent Judges. KAMHOLZ, Administrative Patent Judge. DECISION ON APPEAL Appellants appeal under 35 U.S.C. § 134(a) from the decision of the Examiner to reject claims 1, 3, 4, 8, 11, 24, 25, and 29–41. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. THE CLAIMED SUBJECT MATTER The claimed subject matter is directed to RNAi-mediated inhibition of gene expression in mammalian liver. Claim 1, reproduced below, is illustrative of the claimed subject matter: Appeal 2012-007597 Application 10/259,226 2 1. A method of reducing expression of a target gene in a mammalian cell in a mammalian liver, said method comprising: introducing into said cell in the mammalian liver an amount of a synthetic interfering ribonucleic acid having a 2-nucleotide 3′ overhang and a duplex structure of 19 to 22 nucleotides specific for said target gene effective to reduce expression of said target gene in said mammalian cell. REFERENCES The prior art relied upon by the Examiner in rejecting the claims on appeal is: Weiss Kay US 5,981,279 US 6,107,027 Nov. 9, 1999 Aug. 22, 2000 Tuschl US 2004/0259247 A1 Dec. 23, 2004 Zamore WO 03/006477 A1 Jan. 23, 2003 REJECTIONS Appellants seek our review of the following rejections: Claims 1, 3, 4, 8, 11, 24, 25, 29–35, and 37–41 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Kay and Tuschl. Ans. 6. Claims 1, 8, 30, and 31 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Kay, Tuschl, and Weiss. Ans. 11. Claims 1, 4, 8, 25, and 36 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Kay, Tuschl, and Zamore et al. Ans. 12. ANALYSIS Appellants argue all the rejected claims as a group. We select claim 1 as representative, and the other claims stand or fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(vii)(2011). Appeal 2012-007597 Application 10/259,226 3 The obviousness rejections each are predicated on a reference— Kay—that Appellants argue is not prior art. App. Br. 5. The strength of this argument turns on whether Appellants’ application is accorded the benefit of U.S. provisional patent application Serial No. 60/307,411, filed July 23, 2001. 1 The Examiner takes the position that the ’411 provisional application lacks support for the entire claimed genus of interfering RNAs. Ans. 5. According to the Examiner, claim 1 encompasses RNAi molecules that have a duplex region of 19, 20, 21, or 22 nucleotides, a 2-nucleotide 3′ overhang that may be composed of any nucleotides (for a total of 21, 22, 23, or 24 nucleotides in each strand), and that are directed against any target gene expressed in a mammalian cell in a mammalian liver. Id. According to the Examiner, the ’411 application in contrast discloses only one RNAi, which has a total of 21 nucleotides in each strand, including a duplex region of 19 nucleotides and a 2-nucleotide 3′ overhang composed of two residues of deoxythymidine (dTdT), and targets luciferase. Id. at 5–6. According to the Examiner, the ’411 application does not disclose any RNAi molecules having a 20, 21, or 22-base duplex region. Ans. 15. Appellants present several arguments in response, but the bottom line is that Appellants simply fail to identify disclosure in the ’411 application that indicates they were possessed of RNAi molecules having a duplex region of 20, 21, or 22 nucleotides and a 2-nucleotide 3′ overhang. We do not reach the issue, for example, of how many species within the outer 1 Appellants also rely on the benefit of U.S. provisional patent application Serial No. 60/360,664, filed February 27, 2002. But because this filing date is not early enough to remove Kay as § 102(b) art, we will not consider it further. Appeal 2012-007597 Application 10/259,226 4 boundaries of the genus of Appellants’ claim are necessary to support the claim, because the ’411 application does not disclose even those outer boundaries. There is clear disclosure of an RNAi molecule having a 19- nucleotide duplex region and a dTdT 3′ overhang on page 30 of the ’411 application. 2 Aside from that, however, the only disclosure of RNAi molecules of other sizes is a passing reference on line 13 of the same page to “21- and 22-nucleotide” small interfering RNAs. Even if we assume, without deciding, that this reference amounts to disclosure of an RNAi molecule with a 20-nucleotide duplex region and a 2-nucleotide 3′ overhang, Appellants still have not explained where in the ’411 application they disclosed RNAi molecules with 21- or 22-nucleotide duplex regions. Our careful review of the ’411 application reveals no such disclosure. The upper half (or more) of the claimed size range simply is absent from the ’411 application. For this reason, we agree with the Examiner’s determination that the rejected claims are not entitled to the benefit of the ’411 application. Kay is citable as § 102(b) prior art against the rejected claims. With regard to obviousness, the Examiner takes the position that Kay discloses a method of inhibiting hepatitis C virus in the hepatocytes of a human being by infusing a ribozyme into the individual. Ans. 7 (citing Kay, cols. 6, 10, 14 (Ex. II, III), cl. 1–9). The Examiner argues that, although Kay does not disclose the use of an RNAi molecule for this purpose, Tuschl discloses the use of RNAi molecules, having duplex regions of 19–22 2 This one disclosed RNAi molecule is identical to the “GL3” RNAi molecule disclosed in Elbashir et al., Nature, 411:494–498, 495 (2001). It is also identical to the GL3 RNAi molecule in Tuschl. Tuschl, Fig. 8B, ¶¶ 141–46, pp. 20–21 (SEQ ID NO:18). Appeal 2012-007597 Application 10/259,226 5 nucleotides in length with 2-nucleotide 3′ overhangs, as a “new alternative” to ribozyme therapy for inhibiting gene expression in vivo. Id. at 7–8 (citing Tuschl ¶¶ 10, 34, 137). The Examiner argues that Tuschl provides a “complete blueprint” for the design and use of RNAi. Id. at 9. The Examiner argues that it would have been obvious to substitute Tuschl’s RNAi molecule for Kay’s ribozyme to inhibit hepatitis C virus in vivo in view of Tuschl’s indication that RNAi is a “new alternative” for ribozyme. Id. at 9–10. The Examiner argues that one of ordinary skill would have had a reasonable expectation of success in vivo, given the detailed explanation in Tuschl of how to make and use RNAi molecules and Tuschl’s express disclosure of in vivo use. Id. at 10, 22. Appellants argue that they were the first to demonstrate successful reduction of gene expression in vivo using RNAi. App. Br. 14. Appellants argue that neither Kay nor Tuschl discloses the actual and successful administration of RNAi in vivo, and that the combination of the references yields only a “speculative and non-enabling disclosure” of in vivo administration that provides not “even a remote expectation of success.” Id. Appellant does not apprise us of error in the rejections. The Examiner found, and we agree, that both Kay and Tuschl teach therapeutic administration of nucleic acids. Kay specifically discloses in vivo administration of nucleic acids to liver. Kay, 6:8–36. Tuschl demonstrates successful gene expression reduction in a human tissue-culture system (e.g., 293 cells, ¶ 34) and that RNAi molecules may be formulated as a pharmaceutical composition for in vivo administration (¶ 31). Tuschl expressly suggests the substitution of RNAi for ribozymes (¶ 137). An “obviousness finding was appropriate where the prior art ‘contained detailed Appeal 2012-007597 Application 10/259,226 6 enabling methodology for practicing the claimed invention, a suggestion to modify the prior art to practice the claimed invention, and evidence suggesting that it would be successful.’” In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O’Farrell, 853 F.2d 894, 902 (Fed. Cir. 1988) (emphasis omitted). Here, Tuschl provides detailed information on the method of making the RNAi double stranded molecules, the specific targeting information, and Tuschl demonstrates that RNAi targeting functions in human cell culture. As stated by the Federal Circuit, “[r]esponding to concerns about uncertainty in the prior art influencing the purported success of the claimed combination, this court [in O’Farrell] stated: ‘[o]bviousness does not require absolute predictability of success … all that is required is a reasonable expectation of success.’” Kubin, 561 F.3d at 1360 (citing In re O’Farrell, 853 F.2d at 903-904) (emphasis omitted). Appellants do not cite declaratory evidence in the evidence appendix, nor do Appellants point to any other evidence which would demonstrate a reason to doubt the teachings of Kay and Tuschl regarding in vivo administration of therapeutic nucleic acid. Consequently, balancing Appellants’ argument against the teachings of Kay and Tuschl results in a conclusion that there was a reasonable expectation of success in performing the RNAi treatment method suggested by these references. DECISION For the above reasons, the Examiner’s decision to reject claim 1 is AFFIRMED. Claims 3, 4, 8, 11, 24, 25, and 29–41 are not separately argued and fall with claim 1. Appeal 2012-007597 Application 10/259,226 7 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED lp