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 .
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.
Claims 1-6, 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural products without significantly more. The claim(s) recite(s) nucleic acids comprising SEQ ID NOs: 1-2 or consisting of SEQ ID NOs: 1 or 2. Such nucleic acids are compositions of matter, therefore satisfying Step 1 of eligibility analysis. Specification defines the nucleic acids as portions of natural DNA (see Figure 2A). Such nucleic acids are not structurally different if they are isolated from human genome. Therefore, the claimed nucleic acids are products of nature, satisfying Step 2A Prong One of eligibility analysis. Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 576, 589-90 (2013) (naturally occurring things are "products of nature" which cannot be patented). Accordingly, the claims recite a judicial exception, and the analysis must therefore proceed to Step 2A Prong Two. For analysis in this Step this judicial exception is not integrated into a practical application because claims are drawn to simple products. Because the recited judicial exception is not integrated into practical application, the claims are still directed to judicial exception. Proceeding to Step 2B of eligibility analysis the claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because other limitations in the claims require inclusion in the vector of at least one of nucleic acids, meaning that others can still be present as unmodified nucleic acids, natural products. It is suggested to amend claims to recite vectors comprising the nucleic acids claimed to overcome the rejection.
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) 1-13, 16, 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Diakatou et al (International Journal of molecular sciences, 2019, 20, 2542: 1-22, cited from IDS) and in further view of Yang et al (WO 2019/025984, February 2019, of record) and Slaymaker et al (Science, 2016, vol.351, issue 6268: 84-87).
Diakatou suggest treatment of retinitis pigmentosa (see Title, Abstract) using CRISPR/Cas9 system comprising guide RNAs and Cas9 nuclease (see page 7), such system can be delivered by adeno-associated vector (see last paragraph on page 9). Such treatment can be done to correct c.166G>A autosomal dominant mutation in NR2E3 gene, which is an ideal target for gene therapy (see pages 13, 5).
Diakatou do not teach guide RNA of SEQ ID NOs: 1, or eSpCas9 endonuclease, or administering CRISPR/Cas9 system to iPSC cell, which is further differentiated into retinal progenitor cell.
Yang teach treatment of retinitis pigmentosa (see page 26) by administering genetically modified iPSC cell using CRISPR therapy to the eye of a subject (see page 25). Such iPSC cell can be further differentiated into ocular cell such as retinal progenitor cell (see page 25). CRISPR- associated nuclease and guide RNA can be provided in separate or same vectors such as adeno- associated vector (AAV) and can be a part of pharmaceutical composition (see pages 30, 73). Such CRISPR-based system can be used for treatment of subject in vivo or in vitro through genetic modification of retinal cell and further transplantation of it to the subject (see page 31). Alternatively, iPSC cell can be genetically modified, differentiated and transplanted to the subject (see page 31). Yang teach methods of designing proper guide RNA for CRISPR-based system (see page 71, Figure 12).
Slaymaker teach improved Cas9 endonuclease, eSpCas9 with enhanced specificity and reduced off-target effects (see Abstract). Slaymaker teach design of variety of guide RNAs (see Figures 3, 4, page 87).
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 and use CRISPR-based system to treat retinitis pigmentosa based on teachings of Diakatou , Yang and Slaymaker, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so because Diakatou suggests using CRISPR-based system for treatment of retinitis pigmentosa to correct c.166G>A autosomal dominant mutation in NR2E3 gene. Yang provides specific suggestions on designing CRISPR-based system and applying it in vivo and in vitro for treatment of ocular diseases such as retinitis pigmentosa. Slaymaker teach a new Cas9 protein with improved specificity, reduced off-target effects and design of guide RNAs. None of the references teach instant guide RNA of SEQ ID NO: 1, but Yang and Slaymaker teach design of such guide RNAs. Applying such teachings to NR2E3 gene will yield RNAs comprising instant SEQ ID NO: 1 and others, which can be tested to identify ones providing selecting silencing of mutant allele, especially using enhanced Cas9 endonuclease taught by Slaymaker with reduced off-target effects. Further it is noted that such guide RNAs of instant invention were designed using publicly available software (see paragraph [0173] of instant specification).
Response to Arguments
Applicant's arguments filed 05/05/2026 have been fully considered but they are not persuasive.
Previous 112 rejection and 101 rejection of claim 12 are withdrawn in view of new amendments, arguments are moot.
Concerning 101 rejection of claims 1-6 and 18 Applicant argues that guide RNA is a fusion of two segments and therefore it is not a natural product. In response the newly amended claim 2 recites guide RNA consisting of SEQ ID NO: 1 or 2. Such sequences are products of nature and according to Applicant new amendment guide RNA can consist of only such product. Therefore, rejection is maintained.
Concerning 103 rejection Applicant argues that Diakatou reference does not suggest NR2E3 as a therapeutic target. In response reference explicitly suggests NR2E3 as a therapeutic target on page 13, as it was cited in the rejection.
Further Applicant argues that none of the references teach claimed guide RNAs. In response Yang reference and new Slaymaker reference provide teachings on designing guide RNAs, therefore one of the ordinary skill in the art can design and test them to identify the most efficient ones. Again, it is pointed out that such guide RNAs of instant invention were designed using publicly available software (see paragraph [0173] of instant specification).
Rejection is maintained.
Conclusion
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). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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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