DETAILED ACTION
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/Restriction/Claims
Applicant’s election without traverse of Group I (claims 69-85) in the reply filed on 3/27/2026 is acknowledged. Claims 69-88 are pending. Claims 86-88 are withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 69-85 are the subject of the present Official action.
Priority
Applicant’s claim for the benefit of a prior-filed application 371 of PCTCN2021096122 filed on 5/26/2022 under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 5/26/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7/8/2024, 8/15/2025, 2/9/2026 and 3/27/2026 were received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Claim Objections
Claims 1 is objected to because of the following informalities: the claims contain the acronym DKC1. While acronyms are permissible shorthand in the claims, the first use should include the full recitation followed by the acronym in parentheses.
Claim Rejections - 35 USC § 112b
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 73-76 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 73-76 describe gsnoRNA sequences which are “derived from” wild type H/ACA-snoRNA scaffold sequences. Wild type H/ACA gsnoRNA are a class of small noncoding RNAs which exhibit highly conserved hairpin-hinge-hairpin-tail architecture which act as a structural scaffold for assembling proteins like DKC1 to form pseudouridylation complexes. It is unclear what “derived from” would indicate to one of ordinary skill in the art. “Derived from” could convey several different meanings to one of ordinary skill including degree of gsnoRNA sequence similarity, structural homology any number of core structural characteristics (bipartite hairpins, Hbox, ACA box). Please note that the language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds", see MPEP 2173.
Claim Interpretation
Claim 1 describes a nucleic acid molecule encoding a DKC1 protein which is interpreted as reading on the 1 Dyskerin protein.
Claims 73-76 describe gsnoRNA sequences which are “derived from” wild type H/ACA-snoRNA scaffold sequences. Taking the broadest reasonable interpretation, derived from reads broadly on any sequence or structural similarity to the wild type H/ACA-snoRNA scaffold sequences.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 69, 73-79 and 81-85 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Klein et al. US 2021/0010002, published 1/14/2021, priority date 3/27/2018 (hereinafter Klein).
Claim 69: Klein discloses a method for editing a target RNA in a host cell by converting a uridine to a pseudouridine (Klein, para 8). Klein presents this as a strategy to replace uridine with pseudouridine in stop codons to suppress translation termination, which could be harnessed to mediate readthrough of premature termination codons which are the cause of several genetic disorders (Klein, para 35 and examples 2-4 and claim 15). Klein achieves this by using an engineered guide RNA with the correct structural motif to recruit a host endogenous dyskerin complex (DKC1) that catalyzes the isomerization of uridine to pseudouridine (Klein, para 5, 58).
Claim 73: Klein discloses the basic structure of the wild type H/ACA-snoRNA ACA19 which comprises two hairpin structures within which the internal target-binding loops are located as well as the H box between the hairpins and the ACA box at the 3’ end (Klein, para 18 and Fig 4).
Claims 74-76: Klein discloses the basic structure of the wild type H/ACA-snoRNA ACA19 (Klein, para 18, 36 and Fig 4). As stated in the claim interpretation section, “derived from” is given its broadest reasonable interpretation and reads on any sequence or structural similarity to the wild type H/ACA-snoRNA scaffold sequences. Thus, the disclosure of ACA19 and the other gsnoRNA embodiments provided in para 18 and 19 read on gsnoRNA sequences which are derived from those listed in claim 73 given their shared sequence and structural homology.
Claims 77-78, 80 and 85: Klein discloses the use of a viral vector or plasmid for introducing the nucleic acid encoding the gsnoRNA and dyskerin into a eukaryotic host cell (Klein, para and claim 10-13). Klein discloses the use of a U6 or H1 promoter for expression (Klein, para 36, 47).
Claim 79: Klein discloses encoding the gsnoRNA in an intron sequence which is located between a first exon sequence and a second exon sequence which are derived from a naturally-occurring gene (Klein, claims 9, 19, 25).
Claims 81-82: Klein discloses gsnoRNA comprising chemically modified nucleosides and/or inter-nucleosidic linkages and 5’ cap modifications (Klein, para 8, 45 and claim 3).
Claims 83-84: Klein discloses target RNA including mRNA (Klein, para 54, 61-63). Klein discloses targeting sequences wherein modification of the target uridine to pseudouridine causes the stop codon to be translated as a coding codon (Klein, para 116-117).
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 69-85 are rejected under 35 U.S.C. 103 as being unpatentable over Klein (supra) in view of Heiss et al. WO 99/54449, published 10/28/1999, machine translation provided (hereinafter Heiss) and Angrisani et al. "A new human dyskerin isoform with cytoplasmic localization." Biochimica et Biophysica Acta (BBA)-General Subjects 1810.12 (2011): 1361-1368 (hereinafter Angrisani).
A description of Klein can be found above. Klein does not describe a DKC1 protein which localizes in the cytoplasm of a host cell, comprises the amino acid sequence of SEQ ID NO: 88 or is delivered to the host cell via a viral vector.
Claims 70 and 72: However, human dyskerin isoforms with cytoplasm localization are known in the art as shown by Angrisani. Angrisani used bioinformatics and molecular analysis to identify a DKC1 splice variant able to encode for a truncated form of dyskerin and was able to show stable transduction (Angrisani, abstract).
Claim 71: Similarly, Heiss discloses novel human dyskerin isoforms including one with 100% local similarity to instant SEQ ID NO: 88 (Heiss, sequence search results shown below, claim 8, Fig 1B)
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Claim 80: Both Heiss and Angrisani describe viral expression of the dyskerin isoforms (Heiss, claim 4-6; Angrisani pg 1362).
It would have been prima facie obvious to one of ordinary skill in the art to deliver a dyskerin isoform comprising the amino acid sequence of SEQ ID NO: 88 and/or that localizes in the cytoplasm of a host cell as described by Heiss and Angrisani in the method of RNA editing described by Klein. It would have been a matter of combining prior art elements according to known methods to yield predictable results since the claimed dyskerin isoforms are known in the prior art and are unique in their ability to localize in the cytoplasm rather than the traditional nuclear/nucleolar gsnoRNA pathways that rely on endogenous dyskerin. One would be motivated to make this combination in order to achieve RNA editing outside the nucleus and thus regulate post-transcriptional mRNA networks which are present in the cytoplasm. One would have a reasonable expectation of success given that both Heiss and Angrisani demonstrated that dyskerin isoforms which localize in the cytoplasm can be transduced effectively through viral expression and would therefore be compatible with the programable gsnoRNA editing pathways described by Klein. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
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