DETAILED ACTION
The Amendment filed June 13, 2025 has been entered.
Claims 1-51 are cancelled.
Claim 52 is currently amended.
Claims 52-73 are pending.
Claims 53-58 and 60-73 are withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
All previous objections and rejections not set forth below have been withdrawn.
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 .
Withdrawn Claim Objection
The objection to claims 53-58 and 60-73 is withdrawn in light of the correction of the status identifiers.
Withdrawn Claim Rejection
The rejection of claims 52 and 59 under 35 U.S.C. 103 as being unpatentable over Zhang et al. (U.S. Patent Application No. 2015/0020223, published Jan. 15, 2015) in view of Li et al. (Multiplex and homologous recombination-mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9. Nat. Biotechnol. 2013 Aug;31(8):688-91; published 08 August 2013), Upadhyay et al. (RNA-guided genome editing for target gene mutations in wheat. G3 (Bethesda) 2013 Oct 11;3(12):2233–2238), and Shan et al. (Targeted genome modification of crop plants using a CRISPR-Cas system. Nat. Biotechnol. 2013 Aug;31(8):686-8; published 08 August 2013) is withdrawn in light of the amendment of claim 52.
Claim Rejections - 35 USC § 112
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.
Claims 52 and 59 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 claim(s) 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.
Claim 52 as currently amended is drawn to a method of increasing grain yield of maize crop plant, the method comprising providing multiple guide RNAs by Agrobacterium-mediated transformation to maize embryos from a plurality of maize inbred lines that simultaneously target multiple chromosomal loci conferring multiple traits involved in increasing grain yield of the maize crop plant in association with a Cas polypeptide to introduce a plurality of mutations simultaneously, and generating the maize crop plant that exhibits an increase in grain yield.
Claim 59 is drawn to the method of claim 52, wherein the chromosomal loci are selected from the group consisting of a regulatory element, 5’-UTR, intron, exon, coding sequence, and a promoter.
A method comprising providing multiple guide RNAs by Agrobacterium-mediated transformation to maize embryos from a plurality of maize inbred lines that simultaneously target multiple chromosomal loci conferring multiple traits involved in increasing grain yield of the maize crop plant in association with a Cas polypeptide to introduce a plurality of mutations simultaneously, and generating the maize crop plant that exhibits an increase in grain yield, recited in claim 52, does not find support in the specification as filed, and thus constitutes new matter.
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.
Claim(s) 52 and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (U.S. Patent Application No. 2015/0020223, published Jan. 15, 2015) in view of Armstrong et al. (U.S. Patent No. 6,603,061, issued Aug. 5, 2003), Adams et al. (U.S. Patent Application Publication No. 20090100536, published Apr. 16, 2009), Gao et al. (U.S. Patent No. 8,247,646, issued Aug. 21, 2012), Li et al. (Multiplex and homologous recombination-mediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9. Nat. Biotechnol. 2013 Aug;31(8):688-91; published 08 August 2013), Upadhyay et al. (RNA-guided genome editing for target gene mutations in wheat. G3 (Bethesda) 2013 Oct 11;3(12):2233–2238), and Shan et al. (Targeted genome modification of crop plants using a CRISPR-Cas system. Nat. Biotechnol. 2013 Aug;31(8):686-8; published 08 August 2013).
Claim 52 as currently amended is drawn to a method of increasing grain yield of maize crop plant, the method comprising providing multiple guide RNAs by Agrobacterium-mediated transformation to maize embryos from a plurality of maize inbred lines that simultaneously target multiple chromosomal loci conferring multiple traits involved in increasing grain yield of the maize crop plant in association with a Cas polypeptide to introduce a plurality of mutations simultaneously, and generating the maize crop plant that exhibits an increase in grain yield.
Claim 59 is drawn to the method of claim 52, wherein the chromosomal loci are selected from the group consisting of a regulatory element, 5’-UTR, intron, exon, coding sequence, and a promoter.
Zhang et al. teach a method comprising providing to a plant cell an RNA to target a chromosomal locus in association with a Cas polypeptide to introduce a mutation and generating a crop plant that exhibits an improvement in the agronomic trait (paragraphs [0023], [0032], [0035], [0168], [0169], [0558], [0561], [0659]). The method of Zhang et al. can be used to target chromosomal loci involved in improving one or more agronomic characteristics of a crop plant ([0035], [0168], [0169], [0659]). The method of Zhang et al. can be used to provide multiple guide RNAs that target multiple chromosomal loci to introduce a plurality of mutations simultaneously (paragraph [0659]). The chromosomal loci targeted can include a gene promoter, intron, exon, coding and noncoding sequences (paragraphs [0112], [0464], [0471], [0608], [0610]). Zhang et al. teach that the ability to use CRISPR-Cas systems to perform efficient and cost effective gene editing and manipulation will allow the rapid selection and comparison of single and multiplexed genetic manipulations to transform such genomes for improved production and enhanced traits, and Zhang et al. refer in this regard to U.S. Patent No. 6,603,061 -- Agrobacterium- Mediated Plant Transformation Method, and US 2009/0100536--Transgenic Plants with Enhanced Agronomic Traits (paragraph [0659]). Zhang et al. also teach that the CRISPR-Cas system is a new genome engineering technology that is affordable, easy to set up, scalable, and amenable to targeting multiple positions within a eukaryotic genome, as the system does not require the generation of customized proteins to target specific sequences, but rather utilizes a single protein, the Cas enzyme, that can be programmed by a short RNA molecule to recognize a specific DNA target (paragraphs [0006]-[0007]).
Zhang et al. do not teach increasing grain yield of maize crop plant by providing multiple guide RNAs via Agrobacterium-mediated transformation to maize embryos from a plurality of maize inbred lines that simultaneously target multiple chromosomal loci conferring multiple traits involved in increasing grain yield of the maize crop plant to introduce a plurality of mutations simultaneously, and generating the maize crop plant that exhibits an increase in grain yield.
Armstrong et al. teach a method of transforming a corn (maize) plant cell or plant tissue using an Agrobacterium mediated process comprising the steps of: inoculating a transformable immature embryo from a corn plant with Agrobacterium containing at least one genetic component capable of being transferred to the plant cell or tissue in an inoculation media containing an effective amount of at least one antibiotic that inhibits or suppresses the growth of Agrobacterium; co-culturing the transformable plant cell or tissue after the inoculating step in a medium capable of supporting growth of plant cells or tissue expressing the genetic component, said medium not containing said antibiotic; selecting transformed plant cells or tissue; and regenerating a transformed corn plant expressing the genetic component from the selected transformed plant cells or tissue (claims 1 and 3). Armstrong et al. teach the transformation of maize from a single genotype or from a combination of genotypes, including inbred genotypes (column 9 second full paragraph; Table 28; Table 31).
Adams et al. teach multiple chromosomal loci conferring multiple traits involved in increasing grain yield of a maize crop plant (Table 14, Table 2).
Gao et al. teach that grain yield of a maize crop plant can be increased by utilizing transgenic complementary paired genes controlling maize growth and yield, where specific genes increase female reproductive organs are paired with genes responsible for modifying the growth of non-yield specific plant tissues (paragraph spanning columns 2-3; column 42 Table 2). Gao et al. also teach transgenic maize inbred lines, and Agrobacterium-mediated transformation of maize embryos from maize inbred lines (Examples 1, 3 and 5).
Li et al. teach a method comprising providing multiple guide RNAs that simultaneously target multiple chromosomal loci of the AtRACK1b and the AtRACK1c members of the Arabidopsis RECTOR FOR ACTIVATED C KINASE 1 (RACK1) gene family in Arabidopsis protoplasts, in association with a Cas polypeptide, to introduce a plurality of mutations into the AtRACK1b and the AtRACK1c genes simultaneously, wherein the chromosomal loci are exons (page 690 column 3 first full paragraph and Figure 2; Supplementary Figure 3). Li et al. also teach that the CRISPR-associated protein (Cas) system is a simple, versatile and efficient genome engineering technology that provides for marker-gene independent and antibiotic selection-free genome engineering in diverse plant species (page 688 column 2; page 691 column 2).
Upadhyay et al. teach a method comprising providing multiple guide RNAs that simultaneously target multiple chromosomal loci of the inox (inositol oxygenase) and pds (phytoene desaturase) genes in wheat cells in association with a Cas polypeptide, to introduce a plurality of mutations into the chromosomal loci simultaneously (page 2236). Upadhyay et al. also teach that nontransgenic genome editing in plants is high-priority research for the improvement of food crops, and that the CRISPR-associated protein (Cas) system provides a powerful and effective tool for this purpose (abstract; page 2233 first paragraph).
Shan et al. teach a method comprising providing a single guide RNA that targets the chromosomal locus of the OsPDS phytoene desaturase gene in rice callus cells, in association with a Cas polypeptide, to introduce mutations into the chromosomal locus, and generating a rice plant, wherein the rice plant exhibits an albino or dwarf phenotype (page 686 column 3 second full paragraph and page 687 Figure 1). Shan et al. also teach that the CRISPR-associated protein (Cas) system is an alternative genome editing strategy that is robust, affordable and easy to engineer, and useful for modifying the genome of wheat and rice plants (page 686 first paragraph; page 687 last paragraph).
Given the teachings of Zhang et al. that multiple guide RNAs can be provided in association with a Cas polypeptide to a plant cell to target multiple chromosomal loci involved in improving one or more agronomic characteristics of a crop plant to introduce a plurality of mutations simultaneously, wherein the chromosomal loci targeted can include a gene promoter, intron, exon, coding and noncoding sequences, and wherein a crop plant that exhibits an improvement in an agronomic trait can be generated from such a plant cell, given the further teachings of Zhang et al. that the ability to use CRISPR-Cas systems to perform efficient and cost effective gene editing and manipulation will allow the rapid selection and comparison of single and multiplexed genetic manipulations to transform such genomes for improved production and enhanced traits, including by using Agrobacterium-mediated plant transformation as disclosed in Armstrong et al., and including editing genes that control enhanced traits such as those disclosed in Adams et al., given the teachings of Armstrong et al. that genetic components capable of being transferred to a maize plant cell or tissue can be provided to a maize plant cell or tissue by Agrobacterium-mediated transformation of maize embryos, including maize inbred embryos from maize inbred lines, and that a transformed maize plant expressing the genetic component can be regenerated therefrom, given the teachings of Adams et al. that multiple chromosomal loci conferring multiple traits involved in increasing grain yield of a maize crop plant are known in the art, given the teachings of Gao et al. that grain yield of a maize crop plant, including an inbred maize crop plant, can be increased by utilizing transgenic complementary paired genes controlling maize growth and yield, i.e. cloned genes that correspond to multiple chromosomal loci conferring multiple traits involved in increasing grain yield of a maize crop plant, given the teachings of Li et al. that providing multiple guide RNAs that simultaneously target multiple chromosomal loci to Arabidopsis protoplasts in association with a Cas polypeptide introduces a plurality of mutations into two members of the RACK1 gene family simultaneously, given the teachings of Upadhyay et al. that providing multiple guide RNAs that simultaneously target multiple chromosomal loci of the inox and pds genes to wheat cells in association with a Cas polypeptide introduces a plurality of mutations into the chromosomal loci simultaneously, given the teachings of Shan et al. that providing a single guide RNA that targets the chromosomal locus of the OsPDS gene to rice cells in association with a Cas polypeptide introduces mutations into the chromosomal locus that alter the phenotype of a rice plant generated from the rice plant cells, and given that Zhang et al., Li et al. , Upadhyay et al. and Shan et al. recognize the utility and desirability of the CRISPR-Cas system as a tool for genome editing, 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 provide multiple guide RNAs by Agrobacterium-mediated transformation to maize embryos from a plurality of maize inbred lines that that simultaneously target multiple chromosomal loci conferring multiple traits involved in increasing grain yield of the maize crop plant, in association with a Cas polypeptide, wherein the chromosomal loci targeted can include a gene promoter, intron, exon, coding and noncoding sequences, to introduce a plurality of mutations simultaneously and generate a crop plant that exhibits an increase in grain yield.
One skilled in the art would have been motivated to do so in order to increase in grain yield of a maize crop plant by using a genome editing tool that is recognized in the art as both useful and desirable for editing genes that are known to be associated with important agronomic traits, such as grain yield in maize.
One skilled in the art would have had a reasonable expectation of success, given the success of Armstrong et al. and Gao et al. in utilizing Agrobacterium to transform maize embryos, including embryos from maize inbred lines, given the success of Adams et al. in increasing the grain yield of a maize crop plant by altering the expression of single cloned genes that correspond to individual chromosomal loci each of which confers a trait involved in increasing grain yield of a maize crop using traditional recombinant DNA techniques, given the success of Gao et al. in increasing the grain yield of a maize crop plant by altering the expression of multiple cloned genes that correspond to multiple chromosomal loci conferring multiple traits involved in increasing grain yield of a maize crop using traditional recombinant DNA techniques, given the success of Li et al. and Upadhyay et al. in targeting multiple chromosomal loci in plant cells by providing the cells with multiple guide RNAs that simultaneously target the loci in association with a Cas polypeptide to introduce a plurality of mutations into the loci simultaneously, and given the success of Shan et al. in generating a plant with an altered phenotype from plant cells that have been provided with a single guide RNA that targets a chromosomal locus in association with a Cas polypeptide to introduce mutations into the chromosomal locus.
Thus, the claimed invention would have been prima facie obvious as a whole to a person having ordinary skill in the art before the effective filing date of the claimed invention.
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 CYNTHIA E COLLINS whose telephone number is (571)272-0794. The examiner can normally be reached M-F 8:30 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Shubo (Joe) Zhou can be reached at 571-272-0724. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CYNTHIA E COLLINS/Primary Examiner, Art Unit 1662