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 Status
Claims 1-28 are pending.
Claims 18-25 are being withdrawn from examination as being part of non-elected inventions.
Claims 1-17 and 26-28 are being examined.
All previous objections and rejections not set forth below are withdrawn in view of the claim amendments.
Election/Restrictions
Applicants continue to request rejoinder of non-elected claims (response filed 07/06/2026, p. 10-11). As described in the previous Office action dated 2/6/2026 (p.4, para 5), the requirement for restriction was “deemed proper and is therefore made FINAL”. After a final requirement for restriction, the applicant, in addition to making any reply due on the remainder of the action, may petition the Director to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested. (37 CFR 1.144)
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 9 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. This is a new rejection based on the amendment of claim 9.
Amended claim 9 depends from claim 1 and recites, “… the cis-regulatory element targeted by the one or more guide RNAs is at least 95% identical across plant species.” It is not clear to the Examiner if the claim requires having 95% sequence identity across plant species along the entire length of the “cis-regulatory element targeted by the one or more guide RNAs” or, just the sequence within the “cis-regulatory element being targeted by the one or more guide RNAs”.
To provide better customer service and compact prosecution, the Examiner interprets that the claim requires having 95% sequence identity along the entire length of the “cis-regulatory element targeted by the one or more guide RNAs. In other words, the claim is interpreted as the target cis-regulatory element (e.g., promoter) of the specific gene need to have at least 95% sequence identity across plant species.
It is suggested to delete “targeted by one or more guide RNAs”.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Enablement
Claims 1-17 and 26-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. This is a new rejection necessitated by claim amendments.
Claim 1 recites “A method…(a) generating a set of mutations in a cis-regulatory element of the target gene…with one or more RNA-guided nucleic acid modifying enzymes…one or more different guide RNAs…. each mutation is randomly produced….” (line 6).
The Applicant describes generating a library of independent events (mutations) for multiplexed editing upstream of OsPsbSJ by using eight specific and evolutionarily conserved guide RNA (gRNA) target sites (spec, p.42, para 0092, line 1-3). The design of the gRNAs carefully avoids targeting a putative QTL for NPQ activity in rice upstream of OsPsbSJ gene, an internal 2.7kb Japonica-specific insertion (spec, p.42, para 0092, line 4-6). The Applicant carefully and specifically avoids targeting a putative QTL for NPQ activity upstream of OsPsbSJ gene in Japonica rice to achieve specific gain of function trait(s) viz. increase in photosynthetic efficiency, biomass accumulation, seed yield, crop productivity, and/or water use efficiency (spec, bridging paragraph between p.1-2) via specific pattern (increased expression) of gene expression (spec, p.3, para 0009, line 16-17; p.7, para 0015, last line).
The Applicant does not provide any guidance on how a skilled artisan can randomly produce mutations in specific target gene(s) using CRISPR technology and gRNAs used therein.
Current status of the art does not provide any guidance for any skilled artisan to randomly produce mutations in a target gene using gRNAs and at least one RNA-guided nucleic acid modifying enzyme(s) (Cas endonuclease). CRISPR/Cas system is known to boost expression of specific gene(s) in many ways including by using a (catalytically inactive) Cas endonuclease (e.g. Cas9) fused to a transcriptional activation domain (Cui et al., Review of CRISPR/Cas9 sgRNA Design Tools, 2018, Interdisciplinary Sciences: Computational Life Sciences, 10:455–465; p455, right column, bridging para between p. 455-456) and using and/or inserting one or more cis-regulatory sequence(s) by using different gRNA(s) that positively respond(s) to the transcriptional activation domain fused to the catalytically inactive Cas endonuclease. Guide RNAs also need to have a protospacer sequence complementary to predetermined target site(s) and a protospacer adjacent motif (PAM) in the target site(s). Thus, CRISPR-Cas technique is not known to generate random mutations. Such mutation(s) is/are not random. There is a particular outcome in terms of a targeted/expected mutation in mind by an ordinarily skilled artisan when the artisan design gRNAs and select a specific Cas endonuclease.
Undue trial and error experimentations would be needed to use CRISPR-Cas technique using gRNA(s) and at least one RNA-guided nucleic acid modifying enzyme (Cas endonuclease) to generate random mutations.
Based on breadth of the claims, lack of any working example, lack of guidance in the instant description or in prior art, the specification at the time of the application filed would not have taught one skilled in the art how to make and use the full scope of the claimed invention without performing undue experiments.
New Matter
Claims 1-17 and 26-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection.
Claim 1 recites “…. each mutation is randomly produced….” (line 6).
The Applicant describes generating a library of independent events for multiplexed editing upstream of OsPsbSJ by using eight specific and evolutionarily conserved guide RNA (gRNA) target sites (spec, p.42, para 0092, line 1-3). The design of the gRNAs carefully avoids targeting a putative QTL for NPQ activity in rice upstream of OsPsbSJ, an internal 2.7kb Japonica-specific insertion (spec, p.42, para 0092, line 4-6). The Applicant carefully and specifically avoids targeting a putative QTL for NPQ activity upstream of OsPsbSJ gene in Japonica rice with an objective to develop specific gain of function trait(s) (spec, bridging paragraph between p.1-2) by achieving specific pattern (increased expression) of gene expression (spec, p.3, para 0009, line 16-17; p.7, para 0015, last line).
However, the application as originally filed fails to support, explicitly, implicitly or inherently, to generate randomly produced mutations using gRNA(s) and at least one RNA-guided nucleic acid modifying enzyme (Cas endonuclease). The specification only discusses generating specific and targeted mutations using gRNAs and a RNA-guided nucleic acid modifying enzyme. The response filed 07/06/2026 asserts that support for the claim amendments can be found throughout the original application as filed (p. 9, 1st paragraph). The only passages in the specification discussing gRNA and random mutations, are in paragraphs [0015] and [0033]. Both paragraphs discuss an embodiment of the invention that comprises an inversion in a cis-regulatory element of a PsbS gene. Both paragraphs recite, “In a further embodiment of this aspect,…the inversion in the cis-regulatory element of the PsbS gene was randomly produced in the plant or progenitor thereof. In still another embodiment of this aspect, the inversion was randomly produced using guide RNAs. In yet a further embodiment of this aspect, the guide RNAs include spacer sequences selected from SEQ ID NO: 7…SEQ ID NO: 90”. The specification as filed does not explicitly recite producing random mutations with guide RNAs, other than producing an inversion in the cis-regulatory element of a PsbS gene. Further, it is also noted that, while the specification states, “the inversion was randomly produced using guide RNAs”, a skilled artisan would not consider such inversions to be “randomly” produced, as the guide RNAs would have to be designed to cause the inversion to occur.
Scope of Enablement
Claim 4 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method wherein the plant has a phenotype associated with light signaling, does not reasonably provide enablement for a constitutive phenotype that does not involve light signaling. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. This is a new rejection based on the Applicant’s response dated 7/6/2026.
Claim 4 recites, “… constitutive phenotype…”. (line 2). In the response dated 7/6/2026, the Applicant describes “constitutive phenotype” as “a phenotype that is always present” (response, p.12, para 5, line 2).
The Applicant describes methods of screening for gain of function mutations in non-coding regions of target genes comprising NPQ genes including photosystem II subunit S (PsbS), zeaxanthin epoxidase (ZEP), and violaxanthin deepoxidase (VDE) (spec, para 0003). All these genes are related to light signaling and photoprotective mechanism known as non-photochemical quenching (NPQ) (spec, p.1, para 0004, line 5; p.3, para 0008, line 2-3).
The Applicant does not describe that the at least one of the phenotypes due to overexpression of the target gene(s), all of which are related to light signaling and photoprotective mechanism NPQ, is/are always present in a plant especially during seed setting and initial days of germination before the plant develops light sensing photosynthetic pigments (e.g., chlorophyl) and start photosynthesis using CO2 and water.
It is known in the art that plants generally take about 48 hours (Université de Genève, When the seed becomes a plant, it has 48 hours to survive, ScienceDaily; Published on 2 August 2018) to start developing photosynthetic pigments/organelles and start the process of photosynthesis by utilizing light, CO2, and water to make its own food. At the organelle level, it starts with the development of non-photosynthetic, color-less proplastids to photosynthetically active, green chloroplasts at early stages of plant development, i.e., in germinating seeds, which, in turn, depends on the import of thousands of different preproteins into the developing organelle by the chloroplast protein import machinery (Shanmugabalaji et al., Chloroplast Biogenesis Controlled by DELLA-TOC159 Interaction in Early Plant Development, 2018, Current Biology, 28:2616–2623; Abstract). Moreover, photosynthesis does not occur and photoprotective mechanism NPQ is absent when a plant grows in the dark.
The Applicant does not provide any example or guidance/evidence that overexpression of the target gene(s) can develop trait(s) that is/are constitutive, as currently recited in claim 4.
Undue trial and error experimentations would be needed to develop trait(s) that is/are always.
Based on breadth of the claims, lack of any working example, lack of guidance in the instant description or in prior art, the specification at the time of the application filed would not have taught one skilled in the art how to make and use the full scope of the claimed invention without performing undue experiments.
It is suggested to delete the term “constitutive”.
Written Description
Claim 9 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new rejection based on claim amendments.
Claim 9 depends from claim 1 and recites, “… the cis-regulatory element targeted by the one or more guide RNAs is at least 95% identical across plant species.”
The Applicant describes that NPQ genes are found in all plants, and NPQ proteins are highly conserved in their function (spec, p.2, last para, last 2 lines). The Applicant does not describe if the cis-regulatory elements including the promoter regions in the NPQ genes including the PSBS1 gene in different plant species are highly conserved and having at least 95% sequence identity.
Current status of the art does not describe if the cis-regulatory elements including the promoter regions that regulate the expression of the NPQ genes like PSBS1 is conserved and maintain at least 95% sequence identity across all plant species. Considering the breadth of the claims, lack of representative species from different plant species of the broad genus claimed, lack of structure function relationship of the broad genus claimed, and unpredictability of the art, the Applicant does not appear to have been in possession of the claimed genus at the time this application was filed.
Conclusion
No claim is allowed.
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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bratislav Stankovic can be reached at (571) 270-0305. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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J.C.
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662
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