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 11/26/2025. Claims 78-89 and 92-93 are currently pending. Claims 90-91 have been cancelled. Claims 92-93 are newly added. Claims 85-89 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 78-84 and 90-91 are examined herein. The restriction requirement mailed 03/19/2025 is still deemed proper. Applicant elected the invention of Group I and the species of glucose-6-phosphate-1-dehydrogenase, cas3, an alcohol and lon with traverse in the reply filed 05/19/2025.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Election/Restrictions
Applicant's election with traverse of the invention of Group I and the species of glucose-6-phosphate-1-dehydrogenase, cas3, an alcohol and lon in the reply filed on 05/19/2025 is acknowledged. The traversal is on the ground(s) that the method of Group II cannot be practiced without the microorganism of Group I, and the only fermentation method in which the microorganism of Group I can be applied is the method of Group II. This is not found persuasive because, as discussed in the requirement for restriction/election of 03/19/2025, the microorganism can be used in a materially different process. For example, the microorganism may be used in a single stage process to produce proteins for purification, a process for sequencing its genome, processes comprising further genetic engineering, etc. Regarding Applicant’s arguments that a search for the tool should not be limited to the application of that tool, this argument is not persuasive because, insofar as the claims recite particular genes to be regulated, those genes must be searched and examined. With respect to Applicant’s argument that there is no undue search burden for the recited genes and products, this argument is not persuasive for the reasons discussed in the requirement for restriction/election. In brief, the genes and products are structurally and functionally distinct, and the search terms required to locate prior art regarding e.g., citrate synthase and its functions, pathways and products would not be the same as those required to search for glucose-6-phosphate-1-dehydrogenase, and would likely not lead to the same prior art references. The requirement is still deemed proper and is therefore made FINAL.
Claims 85-89 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/19/2025.
In light of the teachings of Brockman, as discussed below, the species election between deleted genes sspB and cas3 is withdrawn. This reference clearly teaches a microorganism in which the naturally occurring sspB gene has been deleted. The election among the other recited species of deleted genes is maintained.
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.
Claims 78-84 and 92-93 are rejected under 35 U.S.C. 103 as being unpatentable over WIPO Publication 2015/191638 to Brockman (of record; claims priority to provisional application 62/009,672 filed 06/09/2014; hereinafter ‘Brockman’) in view of Qi et al. (Cell. 2013 February 28; 152(5): 1173- 1183.; of record).
A note on claim interpretation: Applicant regards the term, “synthetic metabolic valve” to mean, “the use of controlled proteolysis, gene silencing or the combination of both proteolysis and gene silencing to alter metabolic fluxes.”(para [0051]). The term will be interpreted accordingly. It is relevant to note that the term encompasses either proteolysis, or gene silencing, or both.
Regarding claims 78, 84, and 92, Brockman teaches a genetically modified microorganism (E. coli) comprising: a production pathway comprising at least one enzyme (Pfk-1, INO1) for the production of a product , and at least one synthetic metabolic valve comprising controlled proteolysis (via SspB-dependent degradation controlled by SspB expression from an inducible promoter) of an enzyme (Pfk-1):
Provided herein is a strategy for dynamically modulating the abundance of native enzymes within a host cell using a model system for myo-inositol production from glucose. This system relies on controlled degradation of a key glycolytic enzyme, phosphofructokinase-1 (Pfk-1). Through tuning Pfk-1 levels, an E. coli strain with a growth mode close to wild type and a production mode with an increased glucose-6-phosphate pool available for conversion into myo-inositol was developed. (p. 36 ln 22-28)
the method further comprises expressing in the cell a myoinositol-1-phosphate synthase (INO1). In some embodiments, the method further comprises reducing expression of a glucose-6-phosphate dehydrogenase gene (zwf). (p. 3 ln 31-33)
The invention encompasses any type of cell including prokaryotic and eukaryotic cells. In some embodiments the cell is a bacterial cell, such as Escherichia spp. (p. 28 ln 24-25)
Through addition of an SspB-dependent degradation tag to the coding sequence of Pfk-1, the steady-state level could be controlled by expression of SspB from an inducible promoter. (p. 45 ln 23-25)
Brockman does not teach that the enzyme subjected to controlled proteolysis is the elected species of glucose-6-phosphate-1-dehydrogenase.
However, Brockman does teach that expression of glucose-6-phosphate dehydrogenase (a.k.a. glucose-6-phosphate-1-dehydrogenase), as another enzyme which depletes the pool of glucose-6-phosphate (g6p) by diverting it into the pentose phosphate pathway and therefore competes with INO1 for g6p, may also be controlled using the same approach applied to Pfk-1:
Aspects of the disclosure involve reducing glucose-6-phosphate entry into the pentose phosphate pathway during specific stages of fermentation…glucose-6-phosphate can enter the pentose phosphate pathway by conversion of glucose-6-phosphate to 6-phosphoglucono-1,5-lactone by the glucose-6-phosphate dehydrogenase, Zwf. Glucose-6-phosphate entry into the pentose phosphate pathway can be inhibited by reducing expression of the glucose-6-phosphate dehydrogenase…The expression of glucose-6-phosphate dehydrogenase can be reduced or eliminated by any method known in the art (p. 17 ln 11-12, ln 17-21, ln 23-24)
competition for glucose-6-phosphate (G6P) between native E. coli enzymes (phosphoglucosisomerase and glucose-6-phosphate dehydrogenase) and the first enzyme in the glucaric acid pathway, myo-inositol-1-phosphate synthase (INO1), is also a concern. (p. 57 ln 8-11)
As seen above, Brockman provides a suggestion to control expression of glucose-6-phosphate-dehydrogenase to reduce competition with INO1 and increase the pool of g6p. Brockman further states that this may be accomplished by any methods known in the art. Methods known in the art would necessarily include Brockman’s controlled proteolysis method as applied to Pfk-1.
It is relevant to note that, regarding the limitations wherein under conditions of depleting a limiting nutrient a stationary phase is induced, and wherein the synthetic metabolic valve may be conditionally activated, these limitations are not given patentable weight for two reasons. One: the claim is drawn to a product, and these limitations recite intended uses or conditions of use for the product, but do not change the structure of the product itself. Two: the term ‘may be’ renders the conditional activation in the stationary phase optional. However, it is still relevant to note that Brockman teaches that the activity of pfk-1 can be regulated through systems based on nutrient starvation (p. 71 ln 29).
Brockman does not teach wherein the transcriptional gene silencing comprises expression of small guide RNAs specific for the gene (relevant to claim 78) or that the organism is characterized by disruption of a naturally occurring cas3 gene.
Qi et al. teach the CRISPR interference (CRISPRi) system, which can efficiently repress expression of targeted genes in E. coli (§SUMMARY). Qi et al. further teach that, “the silencing effects of dCas9-sgRNA can be induced and reversed” (p. 4 §CRISPRi Gene Knockdown Is Inducible and Reversible). Therefore, Qi et al. teach controlled transcriptional gene silencing wherein the silencing comprises expression of small guide RNAs specific for the gene. Qi further provides a teaching, suggestion or motivation to use the CRISPRi system, especially in microbes, by noting that, “CRISPRi could provide an RNAi-like method for gene perturbation in microbes” and that it is, “relatively simple”, “does not rely on the presence of complex host factors”, “is flexible and highly designable”, and “can efficiently silence genes in bacteria” with “no detectable off-target effects”.
Brockman also does not teach the system further comprising a valve directed to transcriptional gene silencing, the valve comprising conditional expression of a proteolysis chaperone protein, the chaperone protein required for controlled proteolysis.
However, Brockman teaches conditional expression of the chaperone protein, i.e., expression of SspB from an inducible promoter (see above). As taught by Qi et al. and discussed above, CRISPRi can be used to control expression of targeted genes using an “inducible Cas9 protein” (Figure 2A).
It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the microorganism comprising a synthetic metabolic valve for conditional proteolysis of Pfk-I, as taught by Brock to comprise, to comprise a valve for either conditional proteolysis of glucose-6-phosphate-dehydrogenase using the same method and/or conditional transcriptional gene silencing of glucose-6-phosphate-dehydrogenase using a CRISPRi technology as an alternative method, as taught by Brock and/or Qi. Brock teaches methods of designing proteolytic synthetic metabolic valves, then provides target genes for controlled expression. Brock explicitly suggests controlling expression of glucose-6-phosphate-dehydrogenase to increase the pool of glucose-6-phosphate, and states that this may be accomplished by any methods known in the art. Qi et al. teaches an alternative method which reduces the level of a target protein via controlled gene silencing to redirect metabolic processes. Qi et al.’s teachings amount to the provision of an alternative type of synthetic metabolic valve, and the ordinary artisan would have been motivated to adopt it based on Qi et al’s teachings that CRISPRi is simple, flexible, efficient, and may advantageously be used in microbes such as E. coli, where RNAi is not feasible.
Regarding claim 93, the system described by claims 92 and 93 is interpreted as a system which comprises a proteolytic synthetic metabolic valve, such as that taught by Brockman above, further comprising a valve for conditional expression of the chaperone protein involved in proteolysis. It would further have been obvious, therefore, to substitute the inducible promoter for conditional silencing/expression of SspB with Qi et. al’s CRISPRi system, which is itself inducible and offers the advantage of high specificity, the ability to target multiple genes with one system,
Regarding claims 79-82, please note that claim 78 recites two embodiments of the instantly claimed microorganism: one which comprises a synthetic metabolic valve comprising controlled transcriptional gene silencing, and one which comprises a valve comprising controlled proteolysis. Claims 79-81 all depend from claim 78, and merely limit one of the alternative embodiments recited in claim 78, i.e., the transcriptional gene silencing embodiment and elements thereof. For example, claim 79 states, “wherein transcriptional gene silencing further comprises expression of a gene encoding a dCas9 protein”. The use of the conditional “wherein” is interpreted to mean that if the microorganism comprises the silencing embodiment, then it must also comprise a gene encoding a dCas9 protein. However, that means that the converse is also true: if the microorganism comprises the proteolysis embodiment but does not comprise the silencing embodiment, then the condition is not met, and the gene encoding a dCas9 protein is not required. Therefore, insofar as Brockman teaches/renders obvious the limitations of claim 78 relevant to the proteolysis embodiment, they also teach those limitations as they are present in the dependent claims.
Regarding claim 83, Brock teaches wherein the genetically modified microorganism is characterized by disruption or deletion of a naturally occurring sspB gene:
By appending such a tag to the coding sequencing of Pfk-I and knocking out the native copy of sspB, the half-life of Pfk-I could be controlled through expression of SspB from an inducible promoter. This strategy allowed rapid changes in the steady-state level of Pfk to be achieved. Using this system in E. coli, increases in both titer and yield of myo-25 inositol (MI), a precursor in glucaric acid production were achieved. (p.38 ln 20-25)
Claim 83 is rejected under 35 U.S.C. 103 as being unpatentable over WIPO Publication 2015/191638 to Brockman (of record; claims priority to provisional application 62/009,672 filed 06/09/2014; hereinafter ‘Brockman’) and Qi et al. (Cell. 2013 February 28; 152(5): 1173- 1183.; of record), as applied to claims 78-84 and 92-93 above, further in view of Luo et al. (Nucleic Acids Research, Volume 43, Issue 1, 9 January 2015, Pages 674-681. Published 17 October 2014.; of record)..
Brockman and Qi et al render obvious the invention of claim 78, from which instantly rejected claim 83 depends.
Brockman and Qi et al. do not teach wherein the naturally occurring cas3 is deleted.
Luo et al. teach that, “deleting the cas3 gene from the E. coli genome allowed the targeted and multiplexed regulation of gene expression using the endogenous CRISPR-Cas system” (p. 675). Luo et al. provide a motivation for cas3 deletion, stating, “removal of Cas3 from an endogenous CRISPR-Cas system would allow Cascade to tightly bind target DNA sequences without subsequent degradation. As a result, designed CRISPR arrays would be sufficient to direct targeted DNA binding, thereby blocking RNA polymerase recruitment or extension” (pp. 674-675).
Luo et al. further provide a motivation to delete cas3 to allow CRISPR systems for regulating gene expression, such as that taught by Qi et al., to bind and regulate target DNA without subsequent DNA degradation by cas3.
It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the system as taught by Brockman and Qi et al. to delete the naturally occurring cas3 enzyme. The skilled artisan would have been motivated to combine Qi et al. and Luo et al. to produce a microorganism with a synthetic metabolic valve for controllable transcriptional silencing of glucose-6-phosphate-dehydrogenease expression without interference from native cas3 enzymes.
Response to Arguments
Applicant's arguments filed 11/26/2025 have been fully considered but they are not persuasive for the reasons that follow.
Applicant argues, on p. 7 of the remarks of 11/26/2025, that Brockman fails to teach a synthetic metabolic valve comprising controlled transcriptional gene silencing, as required by the amended claims. This argument is moot in light of the new grounds of rejection above, in which Brockman in view of Qi render obvious an alternative system which comprises conditional gene silencing with CRISPRi instead of controlled proteolysis.
Applicant further argues, on p. 8 of the remarks, that, “page 17, lines 19-28, taken in their full context, make it readily apparent that these methods known in the art are directed to gene knock out and the like and not conditional regulation of a specific gene or enzyme under specific conditions”, and that, “There is simply no teaching or suggestion in Brockman to have selectively regulation [sic] in a conditional manner both the glucose-6-phosphate-1-dehydrogense and Pfk-I genes”. This argument appears to rely on Brockman’s disclosures on page 17, which, among several alternatives, suggest knocking out G6P dehydrogenase. However, in the same text quoted by Applicant, Brockman notes, “Glucose-6-phosphate entry into the pentose phosphate pathway can be inhibited by reducing expression” of the gene (emphasis added). Brockman goes on to note that it is only, “In some embodiments” that “reducing expression” of the gene “comprises eliminating expression”. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (MPEP 2123).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 78, 80-82, 84 and 92-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 19 of U.S. Patent No. 11,142,761 B2 in view of Qi et al. Although the claims at issue are not identical, they are not patentably distinct from each other because the independent claims both recite a genetically modified microorganism with a synthetic metabolic valve that works via either controlled gene silencing or proteolysis, targets the same enzymes, and may be activated in a stationary phase induced by depletion of a limiting nutrient, as shown below:
78. A genetically modified microorganism comprising: a production pathway comprising at least one enzyme for the production of a product, and at least one synthetic metabolic valve comprising controlled transcriptional gene silencing of a gene encoding an enzyme…or controlled proteolysis of an enzyme that is one of: enoyl-ACP reductase, citrate synthase, soluble transhydrogenase, glucose-6-phosphate-l-dehydrogenase, lipoamide dehydrogenase, or combinations thereof
19. A genetically modified microorganism comprising: a production pathway comprising at least one enzyme for the production of a product, and at least one synthetic metabolic valve characterized by (i) controlled transcriptional gene silencing of a gene encoding a first enzyme, or (ii) controlled proteolysis of a second enzyme…wherein at least one of the first enzymes is one of: enoyl-ACP reductase (fabI), citrate synthase (gltA), soluble transhydrogenase (udhA), glucose-6-phosphate-1-dehydrogenase (zwf), or lipoamide dehydrogenase (lpd), or combinations thereof
78. wherein, under conditions of depleting of a limiting nutrient from a growth medium in which the genetically modified microorganism is growing, a stationary phase or non-dividing cellular state is induced wherein depletion of the limiting nutrient from a growth media in which the genetically modified microorganism is growing will inducing a stationary or non-dividing cellular state;wherein the synthetic metabolic valve of the microorganism may be conditionally activated in the stationary phase or non-dividing cellular state.
19. …wherein depletion of the limiting nutrient from a growth media in which the genetically modified microorganism is growing will inducing a stationary or non-dividing cellular state; wherein the synthetic metabolic valve of the microorganism may be conditionally operated
The claims differ in that the gene silencing embodiment of claim 78 requires guide RNAs. However, Qi et al. teaches that controllable transcriptional gene silencing via CRISPRi was known in the art prior to the filing date of the instantly claimed invention. The CRISPRi system performs a function of controlled transcriptional gene silencing equivalent to that specified in the claim. It would have been obvious to use the CRISPRi system as taught Qi et al. to produce an organism with an effective, inducible synthetic valve for controlling transcription of a target enzyme.
Regarding claim 80, Qi et al. teach a single plasmid expressing small guide RNAs for two or more genes, as discussed in the above rejection of the claim under 35 U.S.C. 103. Regarding claims 81-82 and 84, as also discussed above, both the instant and patented claims recite the two embodiments of the invention in the alternative, i.e., either a microorganism with a proteolytic or transcriptional gene silencing control mechanism, and the instantly rejected claims only further limit the silencing embodiment but do not further limit the proteolysis embodiment.
Claims 78, 80-82, 84 and 92-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14 and 16 of U.S. Patent No. 11,268,111 B2 in view of Qi et al. Although the claims at issue are not identical, they are not patentably distinct from each other because the independent claims both recite a genetically modified microorganism with a synthetic metabolic valve that works via either controlled gene silencing or proteolysis, targets the same enzymes, and may be activated in a stationary phase induced by depletion of a limiting nutrient, as shown below:
78. A genetically modified microorganism comprising: a production pathway comprising at least one enzyme for the production of a product, and at least one synthetic metabolic valve comprising controlled transcriptional gene silencing of a gene encoding an enzyme…that is one of:…citrate synthase…glucose-6-phosphate-l-dehydrogenase
14. A genetically modified E. coli, comprising: i. a production pathway comprising at least one production enzyme for biosynthesis of a product…one or more synthetic metabolic valves…the one or more synthetic metabolic valves comprising: a) at least one silencing synthetic metabolic valve that silences gene expression of a gene encoding at least one silenceable enzyme…wherein the silenceable enzyme and the proteolyzable enzyme are each encoded by a gene selected from the group:…gltA…zwf
16. the at least one silencing synthetic metabolic valve is characterized by silencing of gene expression of one, two, three, or four genes encoding enzymes, and the at least one proteolytic synthetic metabolic valve is characterized by controlled proteolysis of one, two, three, or four enzymes, wherein the at least one silencing synthetic metabolic valve and the at least one proteolytic synthetic metabolic valve are the same or different.
78. wherein, under conditions of depleting of a limiting nutrient from a growth medium in which the genetically modified microorganism is growing, a stationary phase or non-dividing cellular state is induced wherein depletion of the limiting nutrient from a growth media in which the genetically modified microorganism is growing will inducing a stationary or non-dividing cellular state;wherein the synthetic metabolic valve of the microorganism may be conditionally activated in the stationary phase or non-dividing cellular state.
14. …wherein growth of the genetically modified microorganism is slowed or stopped by depletion of a limiting nutrient thereby inducing a stationary phase, and product production is enhanced, as compared to a microorganism lacking the production pathway or synthetic metabolic valve, by inducing the synthetic metabolic valve in the stationary phase.
The claims differ in that the gene silencing embodiment of claim 78 requires guide RNAs. However, Qi et al. teaches that controllable transcriptional gene silencing via CRISPRi was known in the art prior to the filing date of the instantly claimed invention. The CRISPRi system performs a function of controlled transcriptional gene silencing equivalent to that specified in the claim. It would have been obvious to use the CRISPRi system as taught Qi et al. to produce an organism with an effective, inducible synthetic valve for controlling transcription of a target enzyme.
Regarding claim 80, Qi et al. teach a single plasmid expressing small guide RNAs for two or more genes, as discussed in the above rejection of the claim under 35 U.S.C. 103. Regarding claims 81-82 and 84, as also discussed above, both the instant and patented claims recite the two embodiments of the invention in the alternative, i.e., either a microorganism with a proteolytic or transcriptional gene silencing control mechanism, and the instantly rejected claims only further limit the silencing embodiment but do not further limit the proteolysis embodiment.
Response to Arguments
Applicant requests that the rejection be held in abeyance pending an indication of allowable subject matter. Per MPEP 804(I)(B)(1), a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated.
Conclusion
No claim is allowed at this time.
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 AMANDA M ZAHORIK whose telephone number is (703)756-1433. The examiner can normally be reached M-F 8:00-16:00 EST.
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/AMANDA M ZAHORIK/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636