DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 2-17-26.
Claims 1-5, 7, 9, 11-18, 23, 25-28 are pending in the instant application.
Claims 4, 5, 7, 9, 11-18 are withdrawn as being drawn to a non-elected species or invention.
Claims 1-3, 23, 25-28 have been examined on their merits as set forth below.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections not repeated in this Office action are hereby withdrawn.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
Claims 1 and 27 is 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.
In line 9 of claim 1, it is unclear whether both stems or one stem comprise 40-80% GC content (e.g. perhaps replacing “the stem comprises” in line 9 to – stems comprise – would be remedial).
Claim 27 depends from itself.
Appropriate corrections are required.
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 1, 2, 23,26, 28 is/are rejected under 35 U.S.C. 103 as being obvious over Green et al (US 2017/0204477) and Arnold et al (RNA, Vol. 4, pages 319-330 (1998)), the combination in view of Wu et al (Cell Systems, Vol. 6, pages 206-215 (2018)).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The claims are drawn to compositions comprising a degradation tuning RNA (dtRNA) comprising a leader sequence comprising less than 18 nucleotides, a first stem-forming region, a loop-forming region comprising 3-6 nucleotides, a second stem-forming region, and an insulator comprising at least five nucleotides, which stem regions are 3-15 base pairs in length and comprise between about 40-80% GC content.
Green et al (US 2017/0204477) teach a nucleic acid construct comprising a promoter operably linked to a sequence encoding a degradation tuning RNA (dtRNA), which dtRNA comprises, from 5' to 3': a leader sequence, a first stem-forming region, a loop-forming region, a second stem-forming region, and an insulator sequence comprising at least five nucleotides; wherein the first stem-forming region and the second stem-forming region form a stem that is at least three nucleotides in length, and which insulator sequence is single stranded (see esp. ¶¶ 0003-0006, 0025-0042, 0058-0085, 0098-0099, 0126-0136, 0214-0217).
Arnold et al (RNA, Vol. 4, pages 319-330 (1998))(see IDS filed 1-13-25) teach stabilization of mRNA by 5’ UTR derived from E. coli ompA. The 5’ UTR of ompA was fused to a variety of mRNAs. Two domains of the 5’ UTR provide the stabilizing effect, a 5’ terminal stem loop and a single stranded RNA segment containing a ribosome binding site. The mRNA protection by the stem loop did not require sequence features or thermodynamic stability beyond that necessary for stem loop formation, and stabilization by the single strand portion is due to high occupancy of the 5’ UTR by bound ribosomes (see the Abstract on page 319).
The primary references do not teach the effects of GC content on reporter expression.
Wu et al (Cell Systems, Vol. 6, pages 206-215 (2018)) (see IDS filed 1-13-25) investigate and report the effects of noncoding regions and other genes in the operon, termed adjacent transcriptional regions (ATR), on gene expression. Synthetic operons were rationally designed and constructed with different synthetic 5’ ATRs containing different GC content and different sizes for tuning protein expression and expression levels (see the Summary and text on page 206). Wu teaches the effects of ATRs on gene expression of a reporter gene for advancing an understanding of the determinants of gene expression in synthetic circuits. The GC content, size and stability of mRNA folding near ribosomal binding sites (RBS) were important features affecting protein translation (Figure 1 and text on page 207, text on page 208). Wu teaches the effects of noncoding sequences on adjacent gene expression in synthetic operons, generating 32 synthetic circuits with 32 genes, placed immediately downstream of the promoter, without RBS to limit their translation. The results showed strong relationship between reporter expression and non-coding 5’ATR GC content, size and local mRNA folding energy. RBS of the ATR was found to provide higher reporter expression, promoting mRNA stabilization and expression efficacy (Figure S2C, Table S1, Figure 2 on page 209).
Increasing GC content from 28% to 53% increased reporter expression. Low GC content downregulated reporter expression about 25-fold (page 211). Wu placed the reporter at different positions to the promoter (i.e. proximal, middle and distal), thereby providing a new expression metric testing the features of ATRs, including GC content, size and stability of mRNA folding near RBS (Figure 2).
It would have been obvious to design and optimize degradation tuning RNA (dtRNA) as instantly claimed because Green had taught all of the components of dtRNA, Arnold taught the importance of two domains of the 5’ UTR in providing the stabilizing effect, a 5’ terminal stem loop and a single stranded of the RNA, and Wu taught the design and testing of synthetic operons constructed with different synthetic 5’ ATRs containing different GC content and different sizes for tuning protein expression and expression levels. One of ordinary skill in the art would have been motivated to optimize and test the dtRNAs as instantly claimed because the significance of the components in the dtRNA as instantly claimed were well known in the art.
For these reasons, the instant invention would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Allowable Subject Matter
SEQ ID Nos.1-6, 10-19, 76-80 appear free of the prior art searched and of record.
Claims 3 and 25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim, pertaining to sequences SEQ ID Nos.1-6, 10-19, 76-80, and any intervening claims.
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.
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
4-23-26
/JANE J ZARA/Primary Examiner, Art Unit 1637
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