Ex Parte Rozners et al

Patent Trial and Appeal BoardSep 7, 2018

14066006 (P.T.A.B. Sep. 7, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 14/066,006 10/29/2013 Eriks Rozners 90150 7590 09/11/2018 Tully Rinckey PLLC 777 Third A venue New York, NY 10017 UNITED ST A TES OF AMERICA 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. SUNY 418.l-P/5739-166 2237 EXAMINER SWITZER, TIJLIET CAROLINE ART UNIT PAPER NUMBER 1634 NOTIFICATION DATE DELIVERY MODE 09/11/2018 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): shoffberg@tullylegal.com steve@hoffberglaw.com uspto@dockettrak.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ERIKS ROZNERS and THOMAS ZENGEY A Appeal2017-009304 Application 14/066,006 1 Technology Center 1600 Before MICHAEL J. FITZPATRICK, ELIZABETH A. LA VIER, and RICHARD J. SMITH, Administrative Patent Judges. LA VIER, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. Â§ 134(a), Appellants seek review of the Examiner's rejections of claims 2-7 and 21-34. We have jurisdiction under 35 U.S.C. Â§ 6(b ). For the reasons set forth below, we AFFIRM-IN-PART. BACKGROUND The Specification describes "a method of forming a PNA-dsRNA[2] triple helix which is stable at physiological conditions, e.g., pH 7.4 and/or 1 Appellants state the real party in interest The Research Foundation for the State University of New York. Appeal Br. 1. 2 PNA = peptide nucleic acid; dsRNA = double-stranded ribonucleic acid. See Spec. 1:14, 1:27. Appeal2017-009304 Application 14/066,006 37Â°C, comprising replacing at least one cytosine of the PNA with a 2- aminopyrimidine nucleobase." Spec. 5:7-9. Claims 2 and 22, the only independent claims on appeal, recite: 2. A method of forming a peptide nucleic acid-double stranded ribonucleic acid (PNA-dsRNA) triple helix which is stable at pH 7.4, comprising: defining a peptide nucleic acid (PNA) sequence having a nucleic acid sequence portion comprising at least one 2- aminopyridine nucleobase configured to selectively bind to a complementary nucleic acid sequence portion conjugated to a peptide sequence portion comprising at least one basic amino acid; and contacting a PNA having the nucleic acid sequence portion with a double stranded RNA ( dsRNA) having the complementary nucleic acid sequence portion to selectively form the PNA- dsRNA triple helix. 22. A method of forming a pH 7.4-stable peptide nucleic acid- double stranded ribonucleic acid triple helix, comprising: providing a peptide nucleic acid sequence having at least one basic amino acid covalently linked to a nucleic acid sequence portion configured to selectively bind to a complementary nucleic acid sequence portion, wherein the nucleic acid sequence portion comprises at least one 2-aminopyridine nucleobase; and contacting a peptide nucleic acid having the peptide nucleic acid sequence with double stranded ribonucleic acid having the complementary nucleic acid sequence portion, to form a peptide nucleic acid double-stranded ribonucleic acid triple helix, in a nucleic acid sequence portion selective manner. Appeal Br. 52-53 (Claims Appendix). 2 Appeal2017-009304 Application 14/066,006 REJECTIONS MAINTAINED ON APPEAL 1. Claims 2-7 and 21 stand rejected under 35 U.S.C. Â§ 112(b) as indefinite. Ans. 2. 2. Claims 2-7 and 22-34 stand rejected under 35 U.S.C. Â§ 103(a) (pre-AIA) as unpatentable over Li, 3 Rusling, 4 Cassidy, 5 and Hildbrand. 6 Ans. 3. 3. Claims 2-7 and 21-34 stand rejected under 35 U.S.C. Â§ 103(a) (pre-AIA) as unpatentable over Li, Rusling, Cassidy, Hildbrand, Hansen, 7 and Sazani. 8 Ans. 6-7. 3 Li et al., Short Peptide Nucleic Acids Bind Strongly to Homopurine Tract of Double Helical RNA at pH 5.5, 132 J. AM. CHEM. Soc. 8676 (2010). 4 Rusling et al., Four Base Recognition by Triplex-Forming Oligonucleotides at Physiological pH, 33 NUCLEIC ACIDS RES. 3025 (2005). 5 Cassidy et al., Recognition of GC Base Pairs by Triplex Forming Oligonucleotides Containing Nucleosides Derived/ram 2-Aminopyridine, 25 NUCLEIC ACIDS RES. 4891 (1997). 6 Hildbrand et al., 5-Substituted 2-Aminopyridine C-Nucleosides as Protonated Cytidine Equivalents: Increasing Efficiency and Selectivity in DNA Triple-Helix Formation, 119 J. AM. CHEM. Soc. 5499 (1997). 7 Hansen et al., High-Affinity Triplex Targeting of Double Stranded DNA Using Chemically Modified Peptide Nucleic Acid Oligomers, 37 NUCLEIC ACIDS RES. 4498 (2009). 8 Sazani et al., Systematically Delivered Antisense Oligomers Upregulate Gene Expression in Mouse Tissues, 20 NATURE BIOTECH. 1228 (2002). 3 Appeal2017-009304 Application 14/066,006 A. Rejection 1 DISCUSSION The Examiner finds that the "contacting" limitation of claim 2 is indefinite because "it is unclear if the PNA that is contacted must also be conjugated to at least one basic amino acid, or if it simply must have 'the nucleic acid sequence portion."' Final Action 2. We agree. It is not clear from claim 2 whether "conjugated to a peptide sequence portion" is a feature of the PNA sequence itself, or of the "complementary nucleic acid sequence portion." Appellants' arguments to the contrary do not persuade us otherwise; instead they illustrate the difficulty of understanding the meaning of claim 2. Appellants assert that "[t]he claim recites a single molecule, which has two conjugated portions." Appeal Br. 8. 9 In their Appeal Brief, Appellants offer only the following further elucidation: The first step of the claim is to define the PNA sequence portion, bearing[ 10J on its complementarity to a nucleic acid sequence, conjugated to the peptide sequence portion. The second step is to contact the defined PNA ("having the nucleic acid sequence portion") with the double stranded RNA. Appeal Br. 8-9. Appellants' fingerprint analogy in the Reply Brief (see Reply Br. 3) sheds little additional light on the matter. Having reviewed Appellants' arguments, we are not entirely sure how Appellants define the "two conjugated portions" (Appeal Br. 8) said to be part of the claimed 9 Claim 2 is directed to a method of forming a PNA-dsRNA triple helix, not the molecule itself. 10 We assume, but not with particular confidence, that Appellants meant "based on," not "bearing on," as we are uncertain as to what the latter implies. 4 Appeal2017-009304 Application 14/066,006 PNA-dsRNA triple helix, nor from where in the language of claim 2 they find support for such delineations. Accordingly, we affirm the rejection of claim 2 as indefinite. Claims 3-7 and 21, which depend from claim 2, are indefinite for the same reasons. B. Rejections 2 & 3 The Examiner'sÂ§ 103 rejections both include independent claims 2 and 22, and both rely on at least Li, Rusling, Cassidy, and Hildbrand. See, e.g., Final Action 9, 40. Because of the indefiniteness of claim 2 as discussed above, and because Appellants grouped all claims together, we tum to claim 22 as illustrative for purposes of our consideration of Rejections 2 and 3. As discussed below, the Examiner erred in concluding that the ordinarily skilled artisan would have had a reasonable expectation of success in combining Li with the other references in the manner of claim 22. Nonetheless, the same error applies to claim 2, despite its uncertain scope, and thus we reverse theÂ§ 103 rejection(s) of claim 2 and its dependents on the same grounds. See Exparte Tanksley, 26 USPQ2d 1384, 1387 (BPAI 1991) (exercising discretion to reach art rejections despite indefiniteness where nature of case permitted). Li, noting that "there are almost no data on triple helices formed by PNA and double helical RNA," offers some data, and ultimately reports that "short pyrimidine PNAs bind strongly and sequence selectively to purine tract of double helical RNA at pH 5.5." Li 8676, 8681. Li ends by stating that "[i]t is conceivable that further development of chemical modifications may allow recognition of isolated pyrimidines in the context of homopurine triple helix at physiological pH, which may provide a novel way to 5 Appeal2017-009304 Application 14/066,006 recognize and interfere with function ofnoncoding RNAs." Id. at 8681 ( footnotes omitted). 11 As the Examiner acknowledges, "Li et al. do not teach contacting a PNA with a 2-aminopyridine nucleobase with a double stranded RNA." Final Action 4. For this, the Examiner turns to Rusling, Hildbrand, and Cassidy. See id. at 4--5. However, as Appellants point out (see Appeal Br. 18-20), these additional references use modified nucleobases to form DNA triple helices; none ofRusling, Hildbrand, or Cassidy works with dsRNA or PNA. This distinction is not fatal to the rejection, see In re Keller, 642 F.2d 413,426 (CCPA 1981) ("But one cannot show non-obviousness by attacking references individually where, as here, the rejections are based on combinations of references."), but it is relevant to our review of the rationale for combining the references. For the rationale to combine the references, the Examiner leans heavily on Li as providing an "express suggestion to use modified nucleobases in an attempt to achieve triplex formation at physiological pH." Final Action 6; see also id. at 4--5, Ans. 17-18. But this "suggestion" from Li, which we quote above, is too general to point the ordinarily skilled artisan in the way of the claimed invention. A combination may be "obvious to try" and obvious under Â§ 103 where there is a design need or market pressure, as well as "a finite number of identified, predictable solutions." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007). But that is not the case here. Instead, Li's guidance (Li 8681) is as unspecific ("further development of chemical modifications") as it is uncertain ("[i]t is 11 One of the omitted footnotes cites to Rusling. 6 Appeal2017-009304 Application 14/066,006 conceivable"). See Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) (quoting In re O 'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) ("[P]rior art fails to provide the requisite 'reasonable expectation' of success where it teaches merely to pursue a 'general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it."')). To the extent that Li points directly to Rusling for Rusling's use of a substituted 2-aminopyridine in forming DNA triplexes at physiological pH (see Rusling 3025), 12 that is still not sufficient to support the rejection. Li details various differences between forming triple helices involving dsDNA as compared to dsRNA (see Li 8676) and challenges particular to developing practical applications of triple helices, i.e., "( 1) slow kinetics of formation and (2) low thermal stability" (id.). Thus we agree with Appellants in their observation that the Examiner seems to take the position that "dsDNA is predictive of dsRNA" (Appeal Br. 20) with regard to triple-helix formation, in order to sweep in the dsDNA-specific references (i.e., Rusling, Hildbrand, and Cassidy for rejection 2). This position is not sufficiently supported on this record, as Li points in the opposite direction. See Li 8676 ("Compared to DNA, the major groove of an RNA double helix is deep and narrow, which may hinder the formation of the triple helix .... Interestingly, DNA as the third strand does not form stable triple helix with RNA, which suggest that short synthetic DNA oligonucleotides cannot be used to recognize double helical RNA." (footnotes omitted)). No other references cited for the 12 Appellants contest this point. See Appeal Br. 20-21. 7 Appeal2017-009304 Application 14/066,006 Â§ 103 rejections relate to forming triple helices including RNA, and Li alone cannot bear the predictive weight the Examiner places upon it. Both Rejections 2 and 3 rely similarly on Li, and similarly cannot be sustained on this record. We reverse Rejections 2 and 3 in their entirety. CONCLUSION Rejection 1 is affirmed. Rejections 2 and 3 are reversed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.I36(a)(l)(iv). AFFIRMED-IN-PART 8