Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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.
Amendments
In the reply filed 5/04/2026, Applicant has amended Claims 7-11, and cancelled Claim 12.
Claims 1-6 and 13-16 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 7-11 are under consideration.
Priority
The instant application was filed Thursday 7/14/2022, and is a CON of 15/905,817 filed 2/26/2018, which is a CON of 14/217,426 filed 3/17/2014, with priority to US provisional 61/789,542 filed 3/15/2013.
In light of Applicant’s arguments and evidence of the revival process, instant claims are being given the filing date of 3/15/2013.
Withdrawn 35 USC § 112(b)
The prior rejection of Claims 7 and 11 under 35 U.S.C. § 112(b), preAIA 2nd paragraph as being indefinite is withdrawn in light of Applicant’s amendments of instant claims to describe the self-reconfiguration.
Withdrawn Claim Rejections - 35 USC § 101
The prior rejection of Claims 7-11 under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter is withdrawn in light of Applicant’s amendment of Claim 7 to limit the invention to a genetic cassette, which does not include an human organism.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of Claims 7-11 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Jakimo et al., (US2014/0349400, filed 3/17/2014, published 11/27/2014). is withdrawn in light of Applicant’s perfection of domestic priority to 3/15/2013, thereby eliminating Jakimo as prior art.
Withdrawn 35 USC § 103
The prior rejection of Claims 7 and 11 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Esvelt et al. (Mol Syst Bio, 2013, 9:641, published Jan 22, 2013), in view of Wang et al. (Meth Enzy, 2011, 498:409-426) and Liu et al. (US2014/0113375, published 4/24/2014, filed 10/19/2013, with priority to 61/716,592 filed 10/21/2012) is withdrawn in light of Applicant’s amendment of Claim 7 to limit the donor RNA to being reverse transcribed to a double stranded DNA construct. Specifically, Liu teaches the donor RNA is reverse transcribed to a single stranded DNA construct.
The prior rejection of Claims 8-10 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Esvelt et al. (Mol Syst Bio, 2013, 9:641, published Jan 22, 2013), in view of Wang et al. (Meth Enzy, 2011, 498:409-426) and Liu et al. (US2014/0113375, published 4/24/2014, filed 10/19/2013, with priority to 61/716,592 filed 10/21/2012), as applied to claim 7, in further view of Collins et al. (US 2012/0003630, filed 12/22/2009, published 1/05/2012) is withdrawn in light of Applicant’s amendment of Claim 7 to limit the donor RNA to being reverse transcribed to a double stranded DNA construct.
New Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 7 and 11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Esvelt et al. (Mol Syst Bio, 2013, 9:641, published Jan 22, 2013, prior art of record), in view of Wang et al. (Meth Enzy, 2011, 498:409-426, , prior art of record), Rozwadowski et al. (WO2003/104470, filed 8/22/2008, published 12/18/2003) and Mali et al. (Science, 2013, 330:823-826, published 2/15/2013)
In regard to claim 7, Esvelt reviews genome-scale engineering for cell systems and synthetic biology. Esvelt teaches the scientific concept of self-reconfiguring genomes comprising sequence modifications to at least two distinct regions of genome in order “to rationally build useful organisms that cannot be easily generated by harnessing evolution alone” (p. 2. 3rd & 4th para.). Specifically, Esvelt teaches in order to [AltContent: textbox ([img-media_image1.png])]make and use a self-reconfiguring genome a CRISPR Cas9 nuclease is employed with a double stranded DNA donor cassette (see Fig 3, “Directed nucleases”, as well as top right “Homologous recombination”, see excerpt adjacent), and that genomic modification via DSB-stimulated HR is accomplished by simply providing an expression cassette comprising the Cas9 and guide RNA spacer sequence matching the target sequence (p. 6-7, RNA-guided CRISPR nucleases, see Fig. 3, bottom left). Esvelt goes on to explain that targeting a wild-type locus with nucleases would catalyze DSB repair using a transgenic cassette as a template, conceptually similar to all-in-one ‘gene-drives’ used to allow self-configuring genomes in transgenic organisms (p. 13, 1st para.).
Thus, Esvelt teaches the scientific concept of self-reconfiguring genomes and reasonable suggests expression cassettes encoding a CRISPR Cas9 and a guide RNA for generating a DSB at a target site, and a donor template for integration into the DSB of the target site in the genome catalyzed by DSB repair.
However, Esvelt is silent to the guide RNA and donor template designed to have the ability to target the promoter region or ribosomal binding sites (RBS) of a target gene.
Nevertheless, Esvelt cites the prior art of Wang (2011), who is a co-author of Esvelt et al., for the making and using of self-configuring genomes that undergo multiplex automated genome engineering (p. 7, 2nd para.).
In regard to claim 7, Wang teaches that the multiplex automated genome engineering targets the nuclease/recombinase to the promoter region and/or RBS of the target gene (p. 413, last para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have prepared the self-reconfiguring genetic cassette as suggested by Esvelt and choose the target sequence for guide RNA directed nuclease cleavage in the promoter region or RBSs of a gene of interest as taught by Wang with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Wang because targeting the promoter region and/or RBS results in the generation of optimal regulatory modules that allow the tuning target gene expression (p. 410, Introduction, 1st para., p. 415, 2nd para., p. 418, last para.).
However, although Esvelt teaches the self-reconfiguring genome can utilize a donor RNA precursor (see Fig. 3, bottom middle), they are silent to donor RNA and a reverse transcriptase, such that the donor RNA is reverse transcribed to a double stranded DNA cassette for homologous recombination with a target site.
In regard to claim 7, Rozwadowski teaches cassettes for modifying the genome of a cells comprising a gene targeting construct comprising a RNA template sequence that codes for a double stranded donor DNA in the presence of a reverse transcriptase (Abstract, pgs. 82-83, Example 7). Furthermore, Rozwadowski teaches the gene targeting construct comprises both the RNA template and reverse transcriptase (p. 83, 2nd para., see also p. 98, 2nd para., and Fig. 14).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to prepared the self-reconfiguring genome cassette as suggested by Esvelt and substitute the donor DNA for donor RNA and a reverse transcriptase as taught by Rozwadowski with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because Rozwadowski teaches that this allows multiple copies of the gene targeting substrate to be produced, thereby increasing the opportunities for the double stranded donor DNA to target a chromosomal locus (p. 6, 1st para., p. 16, last para.). Furthermore, one of ordinary skill would have been motivated to choose a double stranded DNA template for homologous recombination as taught by Mail et al., who Esvelt cites and is a co-author of, and teaches that double stranded DNA templates undergo homology directed repair with a higher efficiency than single stranded DNA templates (Figs 2C, and S10). Finally, it would have been obvious to combine all of the elements (Cas9, gRNA, donor RNA, and reverse transcriptase) into a single construct so as to ensure the host cell was transfected with all the components, and to allow elimination of the single construct after engineering by selective breeding (p. 16, last para. of Rozwadowski).
In regard to claim 11, both Esvelt and Wang teach the target genes to be modified are involved with an organism’s metabolic pathways (p. 1, last para., pgs. 8-9 “Genome-scale metabolic engineering”, see also Fig. 2 of Esvelt, and p. 410, Introduction of Wang)
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 8-10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Esvelt et al. (Mol Syst Bio, 2013, 9:641, published Jan 22, 2013), in view of Wang et al. (Meth Enzy, 2011, 498:409-426), Rozwadowski et al. (WO2003/104470, filed 8/22/2008, published 12/18/2003) and Mali et al. (Science, 2013, 330:823-826, published 2/15/2013) as applied to claim 7, in further view of Collins et al. (US 2012/0003630, filed 12/22/2009, published 1/05/2012, prior art of record)
As discussed previously, Esvelt et al. suggest a self-reconfiguring genome comprising a cassette comprising DNA sequences that code for a CRISPR Cas9 nuclease, guide RNA, and donor RNA that is reverse transcribed into a double stranded DNA template.
However, although Esvelt et al. cite the prior art of Collins et al. throughout the review, they are silent with respect to a counter or data logger that are configured to log the presence of a stimulus.
Nevertheless, Collins et al. (2012) teach a counter or data logger (i.e., single invertase memory module, i.e., SIMM), which can be integrated by targeted insertion into a host cell’s genome, and logs the presence of a small molecule (Abstract, [0009-0011, 0178], see Figs. 1-3).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have prepared the self-reconfiguring genome as suggested by Esvelt and combine a SIMM based counter or data logger as taught by Collins with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Collins because it allows for the maintenance of memory of prior stimulus and provides the ability to count between discrete states (Abstract, [0009]).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 5/04/2026 are acknowledged.
Applicant argues that the RNA of Liu is transcribed only to a single stranded DNA.
Applicant's arguments have been fully considered and they are found persuasive. However, Esvelt in view of Wang have been reapplied in combination of Rozwadowski and Mali who teach that it would have been predictably obvious to combine a donor RNA this is reverse transcribed into a double stranded DNA for genomic integration.
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 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.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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