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 .
Application Status
This action is written in response to applicant’s correspondence received 20 May 2026. Claims 1-2 and 4-20 are currently pending. Claims 1-2 and 4-12 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 13-20 are examined herein. The restriction requirement mailed 25 November 2025 is still deemed proper. Applicant's elected Group II with traverse in the reply filed 20 January 2026.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant' s amendments have been thoroughly reviewed, but are not persuasive to place the
claims in condition for allowance for the reasons that follow.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
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) 13-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Potter ("The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis." Cell 141.3 (2010): 536-548) in view of Dubendorf ("Controlling basal expression in an inducible T7 expression system by blocking the target T7 promoter with lac repressor." Journal of molecular biology 219.1 (1991): 45-59), Persad ("The Q-system as a synthetic transcriptional regulator in plants." Frontiers in plant science 11 (10 March 2020): 245), and Pao ("An N-terminally fused Xenopus transcription factor IIIA synthesized in Escherichia coli is biologically active." Journal of Biological Chemistry 263.21 (1988): 10295-10299). This is a new rejection necessitated by amendment.
Regarding claim 13, Potter is drawn towards the use of a binary expression system based on the regulatory genes from the Neurospora qa gene cluster in order to express transgenes in Drosophila and mammalian cells (Abstract). Potter teaches that the regulatory genes, termed the “Q system”, comprises a transcription factor QF (i.e., a eukaryotic transcription factor) that can bind to the binding site sequence QUAS (i.e., a eukaryotic transcription factor binding site sequence, wherein the eukaryotic transcription factor binding site sequence and the eukaryotic transcription factor are a binding pair) in order to drive expression of a gene that is downstream of the QUAS sequence (pg. 537-538; see Figure 1). Potter teaches that an expression construct encoding c) QF operably linked to either an actin 5c (i.e., for Drosophila cells) or CMV (i.e., for mammalian cells) promoter (i.e., a first promoter) (pg. 537). Potter teaches that a separate reporter plasmid was generated wherein the expression of e) a synthetic firefly luciferase gene (i.e., one or more genes of interest) was placed under the control of d) the QUAS sequence and a Drosophila hsp70 minimal promoter (i.e., a second promoter sequence that is operably linked to the eukaryotic binding site sequence) (pg. 537-538; see Figure 1).
Potter does not teach or suggest that the binary expression system is inducible (Claim 13). Potter does not teach or suggest that the binary expression system is within a single construct (Claim 13). Potter does not teach or suggest that the first and second promoters are prokaryotic (Claim 13). Potter does not teach or suggest that the single construct comprises an operon, wherein the operon is endogenous to a prokaryotic cell (Claim 13). Potter does not teach or suggest the use of a prokaryotic cell comprising the inducible binary expression construct (Claim 20).
Regarding the utilization of prokaryotic promoters in conjunction with an operon that is endogenous to a prokaryotic cell in order to generate an inducible promoter system, Dubendorf is drawn towards a study concerned with the controlling of basal expression in an inducible T7 expression system through the placement of a lac operator (i.e., a lac operon) at different positions relative to a promoter for a T7 RNA polymerase (Abstract). Dubendorf teaches that the lac operator, in the absence of an inducer, comprises a lac repressor that binds tightly to the operator DNA and can thereby interfere with initiation or elongation of transcription by E. coli (pg. 45). Dubendorf teaches that in the presence of inducer, the of repressor for the operator is reduced and transcription can proceed (pg. 45). Dubendorf teaches that when the lac operator is placed downstream of the T7 promoter, at position +15 relative to the T7 promoter, the operon strongly inhibits transcription of the promoter until the inducer IPTG relieved the inhibition of transcription and allows for the T7 RNA polymerase to transcribe the downstream nucleic acid sequence (pg. 49).
Thus, the prior art demonstrates that utilizing an operator that is endogenous to a prokaryotic cell in combination with prokaryotic promoters was a known method of generating an inducible expression construct.
Regarding the successful expression of the QF and QUAS on the same construct in order to drive expression of a gene of interest, Persad is drawn towards a study concerned with the use of the Q-system from Neurospora in plants (Abstract). Persad teaches that when QF is placed on the same plasmid as a QUAS sequence that is upstream of a promoter and reporter, QF is able to interact with the QUAS sequence in order to drive expression of the reporter at a higher rate relative to the reporter linked to just a promoter (pg. 4; see Figure 2).
Thus, the prior art demonstrates that providing QF and QUAS on the same construct is a known method of driving the expression of a gene of interest that is downstream of the QUAS sequence.
Regarding the expression of the eukaryotic transcription factor from a prokaryotic promoter, Pao is drawn towards a study concerned with the expression of a recombinant Xenopus transcription factor TFIIIA (i.e., a eukaryotic transcription factor) from a prokaryotic expression vector containing a prokaryotic lpp/lac promoter (Abstract, pg. 10296; see Fig. 1). Pao teaches that expression of the TFIIIA in E. coli was able to be detected by Western blotting (i.e., the eukaryotic transcription factor was able to be expressed within a prokaryotic cell) (pg. 10297). Pao also teaches that the TFIIIA was able to successfully stimulate transcription in vitro following its purification from the E. coli cells (pg. 10296).
Thus, the prior art demonstrates that eukaryotic transcription factors are able to be successfully expressed from prokaryotic expression plasmids and operably lined to prokaryotic promoters such that their expression is driven in the prokaryotic cell.
Therefore, regarding the linking of the QF and QUAS to first and second prokaryotic promoters, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the binary expression system of Potter such that the QF was operably linked to a T7 promoter upstream of a lac operon and the QUAS was also operably linked to a T7 prokaryotic promoter because it would have merely amounted to a combination of prior art elements according to known methods to yield predictable results. Because Pao teaches that eukaryotic transcription factors can be expressed from prokaryotic plasmids and operably linked to prokaryotic promoters, one would have expected expressing the QF from the inducible T7 promoter construct of Dubendorf to have successfully resulted in the expression of QF in the presence of an inducer that can interact with the lac operon and allow transcription of QF (i.e., resulting in an inducible binary expression system). Additionally, because Dubendorf teaches that RNA Polymerase interacts with the T7 promoter and can drive expression of genes of interest, while Persad teaches that operably linking a QUAS sequence to a promoter can drive expression of a reporter once QF interacts with the QUAS sequence, one of ordinary skill in the art would have expected the linking of QUAS to a T7 promoter to have successfully resulted in the recruitment of a T7 RNA Polymerase to induce expression of the gene of interest following QF interacting with the QUAS sequence.
Regarding the inclusion of both QF and QUAS on the same construct, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the inducible binary expression system rendered obvious above such that the QF and the QUAS were on the same construct because it would have merely amounted to a combination of prior art elements according to known methods to yield predictable results. Because Persad teaches that when QF is placed on the same plasmid as a QUAS sequence the eukaryotic transcription factor performs the same function as when the QF and QUAS are on separate plasmids, and even produces a higher expression level of a reporter plasmid linked to the QUAS sequence relative to a control, one would have expected the inclusion of both QF and QUAS on the same plasmid to have successfully resulted in the interaction of QF with the QUAS in order to drive the expression of the gene of interest following the induction of the expression of QF with an inducer.
Additionally, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the eukaryotic cell of Potter for a prokaryotic cell because it would have merely amounted to a simple substitution of one known element for another to obtain predictable results. Because Pao teaches that eukaryotic transcription factors can be expressed within prokaryotic cells, namely E. coli cells, one would have expected that substituting the eukaryotic cell of Potter for a prokaryotic cell to have successfully allowed for the expression of the eukaryotic transcription factor QF and its cognate binding sequence QUAS. A person of ordinary skill in the art would have expected the substitution to have predictably resulted in a functional QF and QUAS interaction in the prokaryotic cell because Pao teaches that eukaryotic transcription factors can be expressed within prokaryotic cells and detected via Western Blotting (i.e., the eukaryotic transcription factor was successfully expressed within the prokaryotic cell) alongside a disclosure that the expressed transcription factor could stimulate transcription in vitro following purification (i.e., the eukaryotic transcription factor maintained its activity following its expression from the prokaryotic promoter). Additionally, Dubendorf teaches that T7 RNA Polymerases are present within E. coli and can drive expression of a target gene that is downstream of a T7 promoter. Thus, one would have expected the QF and QUAS expressed from the prokaryotic promoters to have allowed for the expression of a functional QF in the prokaryotic cell following induction of the lac operon that allows for the recruitment of T7 RNA Polymerases present within the prokaryotic cell.
Regarding claims 14-16, Potter teaches that the eukaryotic transcription factor is QF and the eukaryotic transcription factor binding sequence is a QUAS sequence (pg. 537-538; see Figure 1).
Regarding claims 17-19, Potter in view of Dubendorf, Persad, and Pao renders obvious the use of T7 promoters and a lac operon to enable inducible control over the expression of the QF, wherein the operon is placed downstream of the prokaryotic promoter but upstream of the eukaryotic transcription factor.
Response to Arguments
Applicant’s arguments with respect to claim(s) 13-20 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
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 KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached Mon-Fri, 9AM-5PM (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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