Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application/Amendment/Claims
Applicant's response filed 05/05/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 02/06/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 05/05/2026, claims 199-205, 207, 210-214 and 219-222 are pending and are currently under examination.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejection not reiterated in this Office Action is hereby withdrawn.
Claim Rejections - 35 USC § 102 – necessitated by claim amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 199-205, 207, 214 and 219 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bettencourt et al. (20140179768).
The claims are interpreted as a double stranded RNA having two strands complementary to each other less than 100 nucleotides, comprises modified nucleotides. The preamble of an ADAR recruiting molecule is not accorded patentable weight because a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951). Therefore any prior art that meets the structural limitations of the claim will be considered as anticipating the claims.
Regarding claims 199-202, 204, 205, 214 and 219, Bettencourt et al. teach a double stranded RNA comprising two complementary strands less than 100 nucleotides in length where the strands comprise terminal base pairs between the complementary strands, phosphorothioate modifications, 2’OMe modifications, end modifications, blunt ends and mismatch base pairs in the center of the duplex (see 0065, 0102, 0111, 0112, 0120-0121).
Regarding claim 203, Bettencourt teach the double stranded oligonucleotides with each strand having 21 nucleotides each comprises backbone modifications positioned within 1-5 nucleotides of a terminal nucleotide (see Table 3, at least SEQ ID Nos. 140/202).
Regarding claim 207, Bettencourt et al. teach the double stranded RNA can further comprising a moiety such as cholesterol (0126).
Thus Bettencourt et al. anticipates the instant claims.
Claim(s) 199-205, 207, 214 and 219 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Aalto et al. (20190352641).
Regarding claims 199, 205 and 219, Aalto et al. teach double stranded oligonucleotide complex comprising an antisense oligonucleotide (AON) and a complementary sense oligonucleotide (SON) annealed to the AON via Watson-Crick base-pairing, for use in ADAR-mediated targeted deamination of a target adenosine in a target RNA sequence in a cell by an ADAR enzyme present in the cell. Preferably, the AON in said AON/SON complex comprises at least one nucleotide that is sensitive to nuclease dependent degradation, and the SON is complementary to the at least one nucleotide that is sensitive to nuclease dependent degradation. More preferably, the SON is complementary to all nucleotides in the AON that are sensitive to nuclease dependent degradation. In a further preferred aspect, the SON comprises a chemical modification assisting in improving a pharmacokinetic and/or a pharmacodynamics property of the complex, wherein the property is selected from the group consisting of: nuclease stability, cellular uptake, intracellular trafficking, and ADAR-mediated AON-guided editing of a target RNA in a cell comprising ADAR (0013). Aalto et al. teach the double stranded oligonucleotide is less than 100 nucleotides, can be the same length (which would be interpreted as having blunt ends) and can comprise mismatch nucleotides which are opposite the adenosine to be edited (see 0036, 0043-0044).
Regarding claims 200-204, Aalto et al. teach the double stranded oligonucleotide (AON/SON) can comprise one or more of backbone and sugar modifications such as phosphorothioate and 2’-O-methyl (0027).
Regarding claim 203, Aalto et al. teach the terminal ends can be modified (0062).
Regarding claim 207, the double stranded oligonucleotide can comprise penetrating particles or nanoparticles for delivery (0065).
Thus Aalto et al. anticipates the instant claims.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 210-214 and 220-222 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of ADAR recruiting molecules comprising double stranded RNAs comprising backbone and sugar modifications, mismatched base pairs, overhang regions, linkers and attached single and double stranded guide RNAs with the function of editing any target gene wherein the ADAR recruiting molecule comprising two double stranded RNA duplexes with a single guide nucleic aicd and linker wherein the duplex region of the two strands is connected to the single-stranded guide nucleic acid via a linker and further double stranded RNA, a first linker connecting the two double-stranded RNA duplexes and a second linker connecting a single stranded RNA to one strand of a double stranded RNA with the function of recruiting ADAR in any cell.
The specification describes these double stranded duplexes recruit RNA editing enzymes such as ADAR and describe examples of just double stranded RNA duplexes with base pair mismatches in Table A , and show in Table 1 editing efficiencies of oligo compositions targeted against a single GAPDH gene.
The specification and claims do not indicate what distinguishing characteristics of the double stranded RNA compositions in Table 1 are concisely shared by the members of the broad genus comprising backbones and sugar modifications, mismatched base pairs, overhang regions, linkers and attached single and double stranded guide RNAs that would convey to one of skill in the art that these RNA duplexes represent the entire genus that would be capable of editing any gene in a cell or subject. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant comprising a vast number double stranded duplexes comprising modified backbones and sugar modifications, mismatched base pairs, blunt mends, linkers and attached single and double stranded guide RNAs, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every double stranded duplex comprising any modified backbones and sugar modifications, mismatched base pairs, blunt ends, linkers and attached single and double stranded guide RNAs with the function of recruiting endogenous ADAR.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Subject matter free of the prior art
The prior art does not teach the structure of the ADAR recruiting molecule as in claims 210-214 and 220-222. Doudna et al. (US 20190276842 of record cited on IDS 09/25/2023) teach the closest prior art comprising a dual guide RNA having a double stranded RNA duplex for RNA editing (see structure below).
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The prior art illustrates the double stranded guide RNA s are connected by a hairpin structure and do not have blunt ends and it would not have been obvious to modified the structure to create blunt ends ad further comprising an additional double stranded RNA duplex alone with a single stranded oligonucleotide attached with linkers.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at 571-272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
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