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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-23, in the reply filed on 04/21/2026 is acknowledged. Species election of base pairs 150-400 of SEQ ID NO: 56 from claim 3, base pairs 350-700 of SEQ ID NO: 56 from claim 4, SEQ ID NOs: 28 and 43 are acknowledged.
Claims 27-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/21/2026.
Claim Rejections - 35 USC § 112
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 3, 4, 11 and 14 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3, 4, 11 and 14 recite the term “preferably”. It is not clear if the limitation following the term is a part of the claim or not, therefore meets and bounds of the claims are unclear. For the purpose of examination it will be considered that the limitations following the term are optional and are not part of the claim.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8 and 13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 8 depends on claim 6 and further defines hexanucleotide repeat as (G4C2)n. There is no other hexanucleotide repeats than (G4C2)n in the sequence, therefore claim 8 does not further limit claim 6.
Claim 13 depends on claim 12 and further defines hexanucleotide repeat as (C4G2)n. There is no other hexanucleotide repeats than (C4G2)n in the sequence, therefore claim 13 does not further limit claim 12.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 22 is rejected under 35 U.S.C. 101 because Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 22 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The broadest reasonable interpretation of the term "cell" embraces a human having the cell. It is suggested to amend the claim to recite "An isolated cell" to avoid the claim embracing a human organism.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cowan et al (WO 2017/109757, June 2017, cited from IDS) and in further view of Konermann et al (Cell, 2018, 173: 665-676, cited from IDS), Lagier-Tourenne et al (PNAS, 2013, E4530-E4539, cited from IDS), Liu et al (Nature Communications, published 8 February 2021, 12, 847: 1-15) and Hsu et al (US 2019/0062724, February 2019).
Cowan teach methods of gene editing of C9ORF72 gene for correction of expanded hexanucleotide GGGGCC repeat (see paragraphs [0010, 0020]) using one of CRISPR-associated endonucleases such as Cas9 to provide targeted cleavage of the gene (see paragraphs [0048, 0183]) and guide RNAs (see paragraph [0051]). Cowan teach designing such guide RNAs and provides a large number of them designed for different endonucleases and spanning the whole transcript of C9ORF72 (see paragraph [0074-0078, 0082-0086]). Such guide RNAs can target 5’ to intron 1 of the gene (see paragraph [00197]). Cowan further teach delivery of endonuclease and guide RNA as nucleic acids encoded in adeno-associated vector and cells comprising such vector (see paragraph [0070]). Cowan further teach pharmaceutical compositions comprising such endonuclease and guide RNA (see paragraphs [0483-0485]).
Cowan do not teach using CasRx/Cas13d endonuclease, or specific target sequences on sense and antisense transcripts of C9ORF72, or specifically targeting variants 1 and 3 of C9ORF72 without affecting variant 2, or guide RNA comprising any of SEQ ID NOs: 1-45, or guide RNA comprising direct repeat sequence of SEQ ID NO: 46.
Konermann teach new, most compact, CRISPR-associated endonuclease CasRx based on Cas13d, which provides high efficiency and specificity and can be easily packaged into adeno-associated virus (see Abstract, Figure 1). Konermann further teach design of guide RNAs (see page 667).
Lagier-Tourenne teach methods of degradation of mutant C9ORF72 genes by administering antisense oligonucleotides targeted to sense and antisense transcripts of the gene (see Title, Abstract) and points out that both transcripts need to be affected for productive treatment (see page E4536).
Liu teach that C9ORF72 produces three transcriptional variants, wherein variants 1 and 3 are the only disease-causing ones (see second column on page 2). Liu suggest design of antisense oligonucleotides specifically targeting variants 1 and 3 without affecting variant 2 (see pages 3-4, Figure 3).
Hsu teach guide RNAs comprising direct repeat sequence of SEQ ID NO: 131 (see paragraph [0355]), which is identical to instant SEQ ID NO: 46. Such guide RNA is associated with CasRx/Cas13d polypeptides (see paragraph [0347]).
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to design a gene editing system comprising CasRx/Cas13d polypeptides with guide RNA targeting different areas of sense and antisense transcripts of C9ORF72 based on teachings of Cowan, Konermann, Lagier-Tourenne, Liu and Hsu. One of the ordinary skill in the art would be motivated to do so, because Cowan teach gene editing system for C9ORF72 using Cas9 protein and teach design of a variety of guide RNAs, and Konermann teach more compact endonuclease CasRx/Cas13d, which can be used in place of Cas9. Further, Cowan and Konermann teach methods of designing of variety of guide RNAs, motivating one of the art to design guide RNAs identical to instant SEQ ID NOs: 1-45. Hsu further teach design of guide RNAs associated with CasRx/Cas13d polypeptides and comprising direct repeat sequence identical to instant SEQ ID NO: 46. Further, Lagier-Tourenne teach methods of degrading C9ORF72 by targeting both sense and antisense transcripts of the gene, motivating one of the art to design guide RNAs targeting such both transcripts. Finally, Liu teach that there are three different variants of C9ORF72, out of which only two are disease-causing ones and suggests targeting only such two variants, without affecting non-disease causing one, motivating one of the art to design guide RNAs following the same approach.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5.
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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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