Ex Parte Allerson et alDownload PDFPatent Trial and Appeal BoardFeb 27, 201310701007 (P.T.A.B. Feb. 27, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte CHARLES ALLERSON, BALKRISHEN BHAT, ANNE B. ELDRUP, MUTHIAH MANOHARAN, RICHARD H. GRIFFEY, BRENDA F. BAKER, and ERIC E. SWAYZE ____________ Appeal 2011-002268 Application 10/701,007 Technology Center 1600 ____________ Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and MELANIE L. McCOLLUM, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims to a composition comprising a double- stranded RNA for use in gene modulation having a contiguous sequence of linked nucleosides in which a nucleoside having a 2'-F substituent group alternates with a β-D-deoxyribonucleoside. The Examiner has rejected the claims as obvious and for obviousness-type double patenting. We have jurisdiction under 35 U.S.C. § 134. We affirm. Appeal 2011-002268 Application 10/701,007 2 STATEMENT OF THE CASE Claims 34, 37, 38, 49, 53-62, 72, 74-78, 94-96, and 104 are pending and stand rejected by the Examiner as follows: 1. Under 35 U.S.C. § 103(a) as obvious over Elbashir, 1 Giese, 2 Fosnaugh, 3 and Morrissey 4 in view of the combined teachings of Arnold, 5 Damha, 6 and McKay. 7 2. On the ground of nonstatutory obviousness-type double patenting as obvious over claims 36, 44, 46-49, 52-64, 74-80, 93, 98-100 and 106 of copending Application No. 10/860,265 (“the „265 application”). 3. On the ground of nonstatutory obviousness-type double patenting as obvious over claims 35-63 of copending Application No. 11/054,848 (“the „848 application”). Appellants did not provide arguments as to Grounds 2 and 3. Consequently, we summarily affirm these rejections. The „265 application, upon which Ground 2 is based, is subject to an Appeal (2011-002405) which has concurrently been decided. The „848 application upon which Ground 3 is based, is subject to an Appeal (2011-002314) which has concurrently been decided. 1 Elbashir et al., Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate, 20 (23) The EMBO Journal 6877-6888 (2001). 2 Giese et al., US 2004/0180351 A1, published Sep. 16, 2004. 3 Fosnaugh et al., US 2003/0143732 A1, published Jul. 31, 2003. 4 Morrissey et al., US 2003/0206887 A1, published Nov. 6, 2003. 5 Arnold, Jr. et al., US 6,262,036 B1, issued Jul. 17, 2001. 6 Damha et al., US 2005/0142535 A1, published Jun. 30, 2005. 7 McKay et al., US 6,133,246, issued Oct. 17, 2000. Appeal 2011-002268 Application 10/701,007 3 An oral hearing was held December 12, 2012. A transcript will be entered into the record in due course. Claim 34 is the only independent claim which is pending and reads as follows: 34. A composition comprising first and second chemically synthesized oligomeric compounds, wherein: the first oligomeric compound is fully complementary to and capable of hybridizing with said second oligomeric compound and to a selected nucleic acid target; at least one of said first and second oligomeric compounds comprises a contiguous sequence of linked nucleosides wherein the sequence defines an alternating motif having the formula: 5'-Q(-L-Z-L-Q)n(-L-Z)nn-3' wherein: each L is an internucleoside linking group; each Q is a nucleoside having a 2'-F substituent group and each Z is a β-D-deoxyribonucleoside; or each Q is β-D-deoxyribonucleoside and each Z is a nucleoside having a 2'-F substituent group; n is from about 8 to about 14 and nn is 0 or 1; and each of said oligomeric compounds is from 12 to 30 linked nucleosides in length. DISCUSSION Claim 34 is directed to a composition comprising first and second “oligomeric compounds,” the first oligomeric compound is fully complementary and capable of hybridizing to the second oligomeric compound. The first or second oligomeric compound “comprises a contiguous sequence of linked nucleosides… [that] define[] an alternating motif” of a specifically recited formula. The formula specifically defines a sequence of alternating nucleosides Q and Z, where Q is a β-D- Appeal 2011-002268 Application 10/701,007 4 deoxyribonucleotide and Z is a nucleoside having a 2'-F substituent, or vice versa. The Examiner rejected the claims over a combination of prior art publications: Elbashir, Giese, Fosnaugh, and Morrissey in view of Arnold, Damha, and McKay. The first group of publications (Elbashir, Giese, Fosnaugh, and Morrissey) describe siRNA duplexes. SiRNA (silencing RNA) is a double- stranded RNA which had been found in the prior art “to specifically and potently disrupt the activity of genes” which contain sequences homologous to the sequences in the siRNA. Spec. 3: ¶ 0008. Claim 34 is directed to a siRNA double-stranded molecule. The second group of publications (Arnold, Damha, and McKay) describe single-stranded antisense RNA. Single stranded antisense oligonucleotides are also known to disrupt gene activity, but by a different mechanism than double stranded siRNA. Answer 18. The Examiner determined that the siRNA prior art described various 2‟ modifications of the ribose sugar of the constituent nucleotides, but not the claimed alternating motif having a 2'-F and β-D-deoxyribonucleoside as alternating nucleosides, where one or both of the self-complementary strands of the siRNA molecule comprise the alternating motif. Answer 7. For the motif, the Examiner turned to the teachings in the antisense prior art of oligonucleotides comprising β-D-deoxyribonucleosides. For example, the Examiner cites Arnold for its teaching of “inhibitory oligonucleotides comprising alternating 2'-[β]-D-deoxynucleosides with 2'-modified nucleosides, and the introduction of these modifications for enhancing target Appeal 2011-002268 Application 10/701,007 5 binding stability.” Id. Damha and McKay were cited for similar disclosures. Id. at 8. We shall reverse the rejection. The Examiner cited Elbashir as teaching “that SiRNA with 2'- deoxynucleotides produced „significantly active siRNAs,‟” providing a reason to have used them in siRNA. Answer 15. However, Elbashir‟s teaching is more limited. Elbashir found in their experiments: Substitution of the 2 nt [nucleotide] 3' overhangs by 2'- deoxynucleotides had no effect and even the replacement of two additional ribonucleotides by 2'deoxyribonucleotides adjacent to the overhangs in the paired region produced significantly active siRNAs. . . . Complete substitution of one or both siRNA strands by 2' - deoxy residues, however, abolished RNAi, as did complete substitution by 2'-O-methyl residues. Elbashir, p. 6881-82. Thus, while Elbashir provided a reason to have used deoxyribonucleosides on the 3‟ end of siRNA, Elbashir‟s teaching that total substitution with deoxyribonucleosides abolished siRNA activity would have deterred a person of ordinary skill in the art from utilizing the deoxyribonucleosides along the entire length of the siRNA. The Examiner also relied upon the antisense prior art for the reason to have used the deoxyribonucleosides along the entire length of the siRNA in an alternating pattern. The Examiner stated: This prior art taught the incorporation of 2'-[β]-D- deoxynucleosides with 2'-modified nucleosides in oligonucleotides for enhancing target binding and stability. Arnold and Damha both stressed the importance of having some deoxyribonucleosides on an antisense strand for Appeal 2011-002268 Application 10/701,007 6 successful oligonucleotide binding to the target nucleic acid molecules . . . Answer 16. However, the teachings about deoxyribonucleotide substitution expressly associated it with the RNaseH mechanism of antisense RNA – a mechanism which does not operate in siRNA. Answer 12; App. Br. 15-16. Thus, one of ordinary skill the art would have not seen such teachings applicable to siRNA. For example, Arnold teaches: As a result, one putative requirement of the antisense RNaseH cleavage approach is that at least some of the nucleosides of the antisense nucleic acid strand must have characteristics in common with deoxyribonucleotides (as opposed to ribonucleotides) . . Arnold, col. 2, ll. 3-7. Likewise, the Monia, et al. report indicates that a minimum of five consecutive 2'-deoxy residues is required in order to achieve efficient activation of mammalian (HeLa) RNAseH, and that this 2'-deoxy segment (if accompanied by 2'- substituted residues in the same antisense compound) must be centered in the oligomer sequence in order to achieve efficient RNaseH activation in vitro or expression inhibition in cells. Arnold, col. 2, ll. 21-28. Similarly, McKay teaches: ISIS Nos. 15346 and 15347 are "gapmers" corresponding to ISIS 12539; both have 2'-methoxyethoxy "wings" (having phosphorothioate linkages in the case of ISIS 15346 and phosphodiester linkages in the case of ISIS 15347) and a central 2'-deoxy "gap" designed to support RNaseH activity on the target mRNA molecule. McKay, col. 38, ll. 40-47. Appeal 2011-002268 Application 10/701,007 7 In making an obviousness determination, “it can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 418 (2007). In this case, the evidence does not support the Examiner‟s rationale for combining the references to have made an siRNA for use in gene modulation having a contiguous sequence of linked nucleosides in which a nucleoside having a 2'-F substituent group alternates with a β-D-deoxyribonucleoside. First, Elbashir‟s results would more likely than not deter one of ordinary skill from incorporating deoxyribonucleotides into the siRNA chain. Second, there is insufficient evidence that the teachings in the antisense prior art about deoxyribonucleoside substitution are pertinent to designing siRNA. The mechanisms of siRNA and antisense RNA are different. Accordingly, we reverse the obviousness rejection 1 of claims 34, 37, 38, 49, 53-62, 72, 74-78, 94-96, and 104. We summarily affirm the obviousness rejections 2 and 3 of claims 34, 37, 38, 49, 53-62, 72, 74-78, 94-96, and 104. 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). Appeal 2011-002268 Application 10/701,007 8 AFFIRMED alw Copy with citationCopy as parenthetical citation