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 .
Applicant’s election without traverse of Group I Claims 1-4, 6-9, 11, 22-23, and 26-27 in the reply filed on 12/10/2025 is acknowledged.
Claims 13, 15-18, and 20-21 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/10/2025.
Priority
This application claims the benefit of priority to U.S. Provisional Patent Application Number 63030222. Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional Application 63030222 filed on 05/26/2020.
This application claims the benefit of priority to Patent Application PCT/US2021/034107. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/US2021/034107, filed on 05/25/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 11/21/2022, 10/18/2023, 04/15/2025, 12/10/2025 has been considered by the Examiner.
Status of Claims
Claims 1-4, 6-9, 11, 22-23 and 26-27 are under examination.
Claims 13, 15-18 and 20-21 are withdrawn.
Claims 5, 10, 12, 14, 19, 24-25, and 28 are cancelled.
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.
Claims 1-4, 6 ,11, 22-23, and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Crisanti et al. (WO-2019243840-A1) in view of Ali et al. (Scientific Reports, 2017).
Regarding claim 1, Crisanti et al. teach a gene editing system comprising (a) a Cas endonuclease (page 64, claim 13), (b) Crisanti et al. teach a regulatory sequence that substantially restricts expression of the second nucleotide sequence to germline cells of the arthropod (page 28, lines 33-35), (c) Crisanti et al. teach the CRISPR-based gene drive genetic construct which hybridizes to the intron-exon boundary of the doublesex (dsx) gene, the first gRNA (page 31, lines 22-28). (d) Crisanti et al. teach a gene drive genetic construct, wherein the first promoter is a polymerase III promoter, optionally a U6 promoter (page 65, claim 16).
Crisanti et al. do not teach a guide polynucleotide targeting a male sterility genomic sequence that is required for male-specific fertility, or a complementary sequence of the guide polynucleotide, or a polynucleotide expressing the guide polynucleotide, wherein the guide polynucleotide targets a gene active during spermatogenesis optionally selected from PTubulin 85D (PTub), fuzzy onions (fzo), protamine A (ProtA), or spermatocyte arrest.
Ali et al. teach a genetically enhanced sterile insect technique against the fruit fly utilizing double-stranded RNAs (page 1, abstract). Ali et al. teach in spermatogenesis occurs at a sex-specific stage to promote male dominant characteristics, which requires the male-specific sequence of the gene double sex male (dsxM) (page 2, paragraph 2). Ali et al. teach Zero Population growth (Zpg) plays a very important role in producing spermless males (page 2, paragraph 2). Ali et al. teach feeding genetically engineered-bacteria that express the target gene dsRNA. Ali et al. teach five testis-specific genes (boul, Zpg, dsxM, fzo and gas8) and their efficacy was assessed (page 5, discussion). Ali et al. teach the most effective gene combinations were boul + zpg, boul + dsxM and zpg + dsxM for pest management applications. Ali et al. teach their method achieved up to 85.40% male sterility. Ali et al. teach highly selective genes involved in spermatogenesis and environmentally friendly approach (page 5, Discussion). Ali et al. teach a silencing effect and male sterility in the target pests in response to target gene dsRNA (page 7, paragraph 2). Ali et al. teach their method provides greater efficiency and a significant reduction in spermatozoa. Ali et al. teach that the selection of target genes is very important. (page 7, paragraph 2).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Crisanti et al. for a gene editing system with the teachings of Ali et al. for the genes to target for the silencing effect and in male sterility in the target pest. Ali et al. provide motivation by teaching that their method provides greater efficiency and a significant reduction in spermatozoa, further teaching that the selection of the proper target gene is important (page 7, paragraph 2). One of skill in the art would have had a reasonable expectation of success at combining Crisanti et al. and Ali et al. because they both teach methods of insect population control.
Regarding claim 2, Crisanti et al. teach a genetically modified insect (page 63, claim 2) or insect egg (page 36, lines 11-12). Crisanti et al. teach the species could be selected from Ceratitis capitata, or Drosophila (page 5, lines 6-12).
Regarding claims 3 and 4, Crisanti et al. teach the insect egg or insect comprises (a) Crisanti et al. teach an insect egg which comprises a polynucleotide encoding an endonuclease which is Cas9 endonuclease (page 64, claim 13). (b) Crisanti et al. teach a regulatory sequence that substantially restricts expression of the second nucleotide sequence to germline cells of the arthropod (page 28, lines 33-35), (c) Crisanti et al. teach the CRISPR-based gene drive genetic construct which hybridizes to the intron-exon boundary of the doublesex (dsx) gene, the first gRNA (page 31, lines 22-28). (d) Crisanti et al. teach the gene drive genetic construct according to, wherein the first promoter is a polymerase III promoter, optionally a U6 promoter (page 65, claim 16). Ali et al. teach a genetically enhanced sterile insect technique against the fruit fly utilizing double-stranded RNAs (page 1, abstract). Ali et al. teach in spermatogenesis occurs at a sex-specific stage to promote male dominant characteristics, which requires the male-specific sequence of the gene double sex male (dsxM) (page 2, paragraph 2). Ali et al. teach Zero growth Population (Zpg) plays a very important role in producing spermless males (page 2, paragraph 2). Ali et al. teach feeding genetically engineered-bacteria that express the target gene dsRNA. Ali et al. teach five testis-specific genes (boul, Zpg, dsxM, fzo and gas8) and their efficacy was assessed (page 5, discussion). Ali et al. teach the most effective gene combinations were boul + zpg, boul + dsxM and zpg + dsxM for pest management applications. Ali et al. teach their method achieved up to 85.40% male sterility. Ali et al. teach highly selective genes involved in spermatogenesis and environmentally friendly approach (page 5, Discussion). Ali et al. teach a silencing effect and male sterility in the target pests in response to target gene dsRNA (page 7, paragraph 2). Ali et al. teach their method provides greater efficiency and a significant reduction in spermatozoa. Ali et al. teach that the selection of target genes is very important. (page 7, paragraph 2). Therefore, Chrisanti et al. and Ali et al. make obvious an engineered insect egg or insect or a progeny thereof which was modified by a gene editing system that targeted genes for a silencing effect and male sterility in target pests.
Regarding claim 6, (a) Crisanti et al. teach an insect egg which comprises a polynucleotide encoding an endonuclease which is Cas9 endonuclease (page 64, claim 13). (b) Crisanti et al. teach a regulatory sequence that substantially restricts expression of the second nucleotide sequence to germline cells of the arthropod (page 28, lines 33-35), (c) Crisanti et al. teach the CRISPR-based gene drive genetic construct which hybridizes to the intron-exon boundary of the doublesex (dsx) gene, the first gRNA (page 31, lines 22-28). (d) Crisanti et al. teach a gene drive genetic construct, wherein the first promoter is a polymerase III promoter, optionally a U6 promoter (page 65, claim 16). (f) Crisanti et al. teach introduction of the polynucleotide to a host cell (page 19, lines 7-10). Crisanti et al. teach the nuclease gene is inserted within its own recognition sequence in the genome such that a chromosome containing the nuclease gene cannot be cut, but chromosomes lacking it are cut. Crisanti et al. teach when an individual contains both a nuclease-carrying chromosome and an unmodified chromosome, heterozygous for the gene drive, the unmodified chromosome is cut by the nuclease (page 46, lines 15-20).
Ali et al. teach a genetically enhanced sterile insect technique against the fruit fly utilizing double-stranded RNAs (page 1, abstract). Ali et al. teach in spermatogenesis occurs at a sex-specific stage to promote male dominant characteristics, which requires the male-specific sequence of the gene double sex male (dsxM) (page 2, paragraph 2). Ali et al. teach Zero growth Population (Zpg) plays a very important role in producing spermless males (page 2, paragraph 2). Ali et al. teach feeding genetically engineered-bacteria that express the target gene dsRNA. Ali et al. teach five testis-specific genes (boul, Zpg, dsxM, fzo and gas8) and their efficacy was assessed (page 5, discussion). Ali et al. teach the most effective gene combinations were boul + zpg, boul + dsxM and zpg + dsxM for pest management applications. Ali et al. teach their method achieved up to 85.40% male sterility. Ali et al. teach highly selective genes involved in spermatogenesis and environmentally friendly approach (page 5, Discussion). Ali et al. teach a silencing effect and male sterility in the target pests in response to target gene dsRNA (page 7, paragraph 2). Ali et al. teach their method provides greater efficiency and a significant reduction in spermatozoa. Ali et al. teach that the selection of target genes is very important. (page 7, paragraph 2). Therefore, Chrisanti et al. and Ali et al. make obvious an engineered insect egg or insect or a progeny thereof which was modified by a gene editing system that targeted genes for a silencing effect and male sterility in target pests.
Regarding claim 11, Crisanti et al. teach there is no reduction in fitness in females with only one copy of the target gene (page 48, lines 2-5). Regarding claim 22, Crisanti et al. teach suppressing a wild type arthropod population (page 37, lines 4-5). Crisanti et al. teach a method of progressively reducing the egg production to the point of total population collapse (page 59, lines 11-14).
Regarding claim 23, Crisanti et al. teach a method of producing (1) a genetically modified insect egg (page 69, claim 36), (2) a genetically modified insect (page 69, claim 37), (3) a population comprising the genetically modified insect egg or the genetically modified insect (page 69, claim 41). Crisanti et al. teach introducing gene drive genetic construct capable of disrupting an intron/exon boundary of the female specific splice form of doublesex gene in an arthropod. Crisanti et al. when the gene-drive construct is expressed the arthropod exhibits a suppressed reproductive capacity (page 69, claim 37).
Regarding claim 26, Crisanti et al. teach a composition comprising a carrier of the gene driver system (page 45, lines 26-30).
Regarding claim 27, Crisanti et al. teach a method/provide instructions for progressively reducing the egg production to the point of total population collapse (page 59, lines 11-14), which are the components of a kit.
Claims 7-9, are rejected under 35 U.S.C. 103 as being unpatentable over Crisanti et al. (WO 2019/243840) in view of Ali et al. (Scientific Reports, 2017) as applied to claims 1-6 and 8 above, and further in view of Nandy et al. (Plant Direct, 2019).
Crisanti et al. and Ali et al. make obvious a genetically modified insect or insect egg, where a gene active during spermatogenesis was targeted. Crisanti et al. make obvious that the species could be selected from Ceratitis capitata, or Drosophila.
Regarding claims 7-9, Crisanti et al. and Ali et al. teach the insect population with a Cas9 endonuclease.
Crisanti et al. and Ali et al.do not teach expression of the endonuclease is not activated and the insect egg or the insect or the insect population or a progeny of each thereof of is kept under a permissive temperature of the regulatory sequence of (b)regulatory sequence directing the endonuclease expression in a cell, optionally wherein the cell is an insect germline cell, optionally wherein the regulatory sequence is temperature-sensitive, and further optionally wherein the regulatory sequence comprises a heat-shock protein 70B (Hsp70Bb)promoter.
Nandy et al. teach a heat-shock-inducible CRISPR/Cas9 system. Nandy et al. teach sequences ending with noncanonical PAMs such as NAG can also be targeted by Cas9, and while chromatin structure plays a marginal role in targeting, the secondary structures in the target DNA and the sgRNA could allow significant pairing, in spite of the mismatches at the PAM end. Nandy et al. teach in mammalian cells, higher concentrations or the constitutive expression of sgRNA:Cas9 reportedly induced a high rate of off‐target mutations (page 11, paragraph 1). Nandy et al. teach inducible expression systems can be argued as more versatile transient expression systems, provided they generate low or undetectable background expression and a high‐induced expression. Nandy et al. teach heat‐shock promoters have been successfully used in applications where their proper regulation was critical (page 11, paragraph 2). Nandy et al. teach a HS‐inducible CRISPR/Cas9 system which is generally suppressed at the ambient room temperature and activated by the heat‐shock treatment. Nandy et al. teach the heat‐shock‐induced genome editing is efficient at producing heritable targeted mutations, while curbing the off‐target mutations. Nandy et al. teach HS‐CRISPR/ Cas9 is a promising genome editing tool that can provide temporal control toward improving the precision of the CRISPR/Cas9 activities (page 12, paragraph 2).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the teachings of Crisanti et al. and Ali et al. for the modified insect population utilizing an endonuclease with the teachings of Nandy et al. for a heat-shock-inducible CRISPR/Cas9 system. Nandy et al. provide motivation by teaching that teach the heat‐shock‐induced genome editing is efficient at producing heritable targeted mutations, while curbing the off‐target mutations. One of skill in the art would have had a reasonable expectation of success at combining Crisanti et al., Ali et., and Nandy et al. because both utilize CRISPR/Cas9 for gene modification.
Conclusion
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635