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, 4-5, 7, 9, 11-15, 21-22, 28-41, and 43-57 are pending.
Claims 28-41 and 44-56 are withdrawn as being drawn to a non-elected invention.
Claims 1 and 57 are newly amended.
Claims 1, 4-5, 7, 9, 11-15, 21-22, 43 and 57 are rejected.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. [119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The instant application claims benefit from three priority filings, 62/676,564 filed 05/25/2018, 62/783,537 filed on 12/21/2018, and PCT/US19/33907 filed on 05/24/2019.
The disclosure of the prior-filed applications, Application No. 62/676,564 and Application No. 62/783,537, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The examined claims all require introducing into a plant's genome HEI10, MSH4, MSH5, SHORTAGE OF CROSSOVERS1 (SHOC1) XPF nuclease or PARTING DANCERS (PTD). The two provisional applications do not even mention these terms and do not provide enough support for these limitations.
The disclosure of the prior-filed application, Application No. PCT/US19/33907 recites introducing into a plant's genome HEI10, MSH4/MSH5, Mlh1/Mlh3, MutS-related heterodimer, MER3 DNA helicase, SHORTAGE OF CROSSOVERS1 (SHOC1) XPF nuclease, PARTING DANCERS (PTD), ZIP4/SPO22, Zip1, Zip2, Zip3, Zip4, Msh4, Msh5, Mlh1/Mlh3 gene, or combinations thereof in claim 17 of PCT/US19/33907 and describes them in at least the first paragraph of page 6 of PCT/US19/33907.
Therefore, the instant application is treated with the priority date of 05/24/2019.
Response to Applicant Arguments – Claim Objections
Applicant’s amendments to the claims dated 04/20/2026 have been fully considered but are not found to be persuasive and the claim objection of record is maintained. Further, Applicant’s amendments to the claims requires new claim objection against claim 1.
Claim Objections
Claim 1 remains objected to because of the following informalities: Applicant has amended the claim and the new amendments recite gene abbreviations earlier in the claim than the full names. In order to correct this the claims should be amended to recite the full name of the gene followed by the abbreviation in parenthesis the first time that the gene is mentioned.
Appropriate correction is required.
Claim 1 is newly objected to because of the following informalities: in line 11 of the claim, Applicant has amended the claim to recite a list of genes which have their copy number increased, this list includes “(SHOC1)XPF nuclease”. This recitation is incomplete as demonstrated by lines 15-16 which recites “SHORTAGE OF CROSSOVERS1 (SHOC1) XPF nuclease”. While the recitation in claim 11 by itself may be indefinite given that there are many non-SHOC1 XPF nucleases and the use of parenthesis in that recitation make it unclear if the claim is limited to SHOC1 or to any XPF nuclease, the recitation in lines 15-16 demonstrates that SHOC1 refers to the SHORTAGE OF CROSSOVERS1 XPF nuclease and therefore the scope imparted on the claim by the recitation of “(SHOC1) XPF nuclease” is definite. However, given that this is the first recitation of that abbreviation in the claim the claim should be amended to recite the full name followed by the abbreviation in parenthesis.
Appropriate correction is required.
Response to Applicant Arguments - 35 USC § 112 (Written Description)
In response to Applicant’s arguments and amendments made 04/20/2026 the written description rejections of record are withdrawn.
Response to Applicant Arguments - 35 USC § 103
Applicant’s arguments and amendments made 04/20/2026 have been fully considered but are not found to be persuasive.
Applicant’s arguments with respect to these rejects are found on pages 5-7 of the remarks dated 04/20/2026 and are drawn to the following:
The office action cites to Smith to teach the claim limitation “introducing the selected candidate plant or the population of candidate plants into a breeding population”, however these teachings of Smith differ from the claimed methods. Specifically, in the cited section, Smith teaches the identification of a marker-trait association in a non-adapted germplasm and the use of that same non-adapted germplasm in breeding programs. In contrast the instantly claimed methods require that the selected candidate plants do not comprise the introduced genetic modifications and are not obtained from the population of plants that contain the introduced genetic modifications making clear that the association is identified in a different population than the one from which candidate plants are selected and used the breeding program. Smith does not teach this and the office action does not make clear why the prior art would have been combined in this way and as such it would require impermissible hindsight for the ordinary artisan to arrive at the claimed method.
These arguments are not found to be persuasive.
First, the Examiner agrees with Applicant that Smith provides general teachings of introducing candidate plants having an identified marker-trait association into a breeding population.
However, in combination the method of Smith in view of Cockram, Ziolkowski and Shi teaches a method for selecting a plant with a trait of interest. This method involves producing an enhanced mapping population by increasing recombination rates. This creates conditions optimal for fine mapping but has another inherent characteristic. The genomes of these populations have a structure that is not optimal for a role in a breeding population. Specifically, the plants in these populations have less stable genomes and are optimized for discovery of marker-trait associations. It would therefore have been obvious to use genomic selection to identify an elite line of that plant comprising the marker for use in the breeding population because as noted in Cockram, “Because selection and phenotyping are decoupled, very high intensities of selection are possible (because single individuals rather than cultivars are selected) and reductions in cycle time can be made” (Cockram, Page 112, Second Paragraph). This teaching of Cockram makes clear that identifying markers in one population and then applying their use to individual plants in another population allows for a high degree of selection and decreased time in adding a trait to a breeding population.
Therefore, given these implicit characteristics of the method of Smith in view of Cockram, Ziolkowski and Shi in combination with the teaching from Smith that plants having a desirable marker-trait association should be introduced into a breeding population Applicant’s arguments are not found to be persuasive.
Further, it is well known in the art that mapping occurs in populations adapted to that and that the discovered associations are then applied to distinct breeding populations (Wurschum, Page 201, Paragraph Spanning Columns 1-2)( Würschum, Theoretical and Applied Genetics 125.2 (2012): 201-210).
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 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.
Claims 1, 4-5, 7, 9, 11-15, 21-22, 43 and 57 remain rejected under 35 U.S.C. 103 as being unpatentable over Smith, in view of Cockram, Ziolkowski, and Shi.
Independent claim 1, is drawn to a method of selecting a plant with a trait of interest. The major steps of the method are summarized as follows:
Generating or obtaining a population of plants comprising a modification that increases meiotic recombination.
Using the population of modified plants to identify a marker-trait association of a trait of interest wherein
the population of plants has had one or more genetic modifications that increase the copy number of an endogenous HEI10, Msh4, Msh5, SHOC1 XPF nuclease, or PTD gene using genome editing, or
the population of plants has had one or more genetic modifications in the promoter region of an endogenous HEI10, Msh4, Msh5, SHOC1 XPF nuclease, or PTD gene using genome editing
to increase the expression level of the endogenous gene.
Screening a candidate population of plants for the marker for the trait of interest, wherein the candidate population of plants does not comprise the introduced genetic modifications and are not obtained from the population of plants that contain the introduced genetic modifications.
Selecting a candidate plant from a population of plants that does not include any from the population, based on the presence or absence of the marker for the trait of interest, growing the selected candidate plant and introducing the selected candidate plant or population of candidate plants into a breeding program.
With respect to claim 1, Smith teaches a method of selecting a plant with a trait of interest (Smith Page 59, Claim 52, Line 1), the method comprising: providing a data set comprising genotypic and/or phenotypic data obtained from a population of plants, Smith teaches providing an association between at least one genetic marker and the phenotypic trait (Data set) in a first plant population(Smith, Page 59, Claim 52, Lines 2-7), wherein the population of plants comprises one or more phenotypic or genotypic markers; Smith teaches an association between at least one genetic marker (Smith, Page 59, Claim 52, Line 2).
Additionally, Smith teaches identifying or generating one or more marker-trait associations in the data set that correlate with the trait of interest in the population of plants; Smith teaches providing an association between a marker and a phenotypic trait of interest in the first plant population (Smith, Page 59, Claim 52, Part (a).
Further Smith teaches screening a candidate plant or a population of candidate plants for the presence or absence of the one or more marker-trait associations that correlate with the trait of interest ; Smith teaches selecting a plant from a non-adapted second population wherein the selected plant has the genetic marker associated with the phenotypic trait, Smith does not teach a first population with an introduced genetic modification that leads to increased recombination but it does teach a first population which is better suited (adapted) to identifying a marker-trait association, as evidenced by the selection taking place in a non-adapted plant population(Smith, Page 59, Claim 52); and selecting the candidate plant based on the presence or absence of the one or more marker-trait associations that correlate with the trait of interest(Smith, Page 59, Claim 52, Part B). Finally, Smith teaches breeding the at least one selected plant having the selected genotype and the desirable value of the phenotypic trait with at least one other plant and Smith also teaches that the methods of Smith have uses in applied breeding programs because the methods allow for the prediction of phenotypic performance of potential progeny which can be used to select plants for use as parents in one or more further crosses (Smith, Page 60, Claim 65; Smith, Pages 17-18, Paragraph 0074).
With respect to claim 1, Smith does not teach the use of a first plant population having increased genetic recombination due to a genetic modification and growing the selected plant.
With respect to claim 1, Cockram teaches that it would be beneficial to conduct mapping studies in populations having higher recombination rates as is provides more accurate mapping (Cockram, Page 109, Abstract, Sentences 3-4, and 6). Further, Cockram teaches the use of genomic selection to apply statistical models to use a high selection intensity to apply genetic markers to predict breeding values to a separate population of plants that are not members of the mapping population (genotyped plants) (Cockram, Page 112, Second Paragraph). Cockram teaches that in addition to allowing for the application of a high degree of selection pressure, this allows for faster integration of marker-trait associations into a breeding population because it avoids the development of a cultivar and uses individual plants (Cockram, Page 112, Second Paragraph).
With respect to claim 1, Ziolkowski teaches mutant Arabidopsis thaliana plants having null hei10 mutations are haploinsufficient (Ziolkowski, Page 306, Abstract). Importantly, Ziolkowski teach that transformation of these mutant plants with additional copies of wild-type HEI10 more than doubles euchromatic crossovers (Ziolkowski, Page 306, Abstract). In fact, Ziolkowski teaches that “increased HEI10 dosage and expression level elevates crossovers throughout the genome” (Ziolkowski, Page 312, Column 2, First Full Paragraph). For clarity, Ziolkowski also teaches that cross over events are responsible for recombination and therefore the plants of Ziolkowski with increased crossovers also have increased recombination rates (Ziolkowski, Page 306, Column 2, First Full Paragraph; Ziolkowski, Page 307, Column 1, First Full Paragraph).
With respect to claim 1, Shi teaches the use of CRISPR-Cas-enabled advanced breeding technology to insert a constitutive promoter into the 5’ untranslated region of a target gene or to replace the native promoter of the target gene (Shi, Page 207, Abstract). Shi teaches that these modifications lead to elevated levels of the gene of interest in all tissues tested as compared to the native allele (Shi, Page 207, Abstract). Finally, Shi teaches that this technique allows for the production of new sources of genetic variation for plant breeding and represents a seminal addition to the precision breeding toolbox that can enhance changes to the plant genome (Shi, Page 213, Column 1, First Full Paragraph, Last two sentences).
At the time of filing it would have been obvious to the ordinary artisan to modify the method of Smith in order to conduct the marker association step in a population having increased recombination as described by Cockram through the overexpression of HEI10 by replacing the native HEI10 promoter with a constitutive promoter as taught in Ziolkowski and Shi respectively and to select plants having this association from a distinct population as taught by Cockram and to grow the selected plant and further to use that plant to make crosses in a breeding program as taught by Smith.
This would have been obvious because the method of Smith is drawn to mapping traits to genetic loci associated with identifiable markers and Cockram provides motivation to practice this type of method in plants having increased recombination rates because Cockram teaches that increasing recombination increases the accuracy of these types of methods. Further, Ziolkowski teaches that increasing expression of HEI10 leads to higher recombination rates and Shi teaches that using gene editing to swap promoters in a gene of interest with a constitutive promoter increases target gene expression.
Therefore, Smith teaches a base method, Cockram teaches a modification to the method that would improve the method by increasing accuracy and teaches the benefits of selecting plants in a distinct population from the mapping population, and Ziolkowski and Shi teach a method to increase HEI10 expression and recombination rate. These methods are all drawn to methods in the field of plant molecular biology related to plant and crop improvement.
The ordinary artisan would have been motivated to combine these methods because it would increase the accuracy and efficiency of methods for identifying molecular markers associated with important traits and improve efficiency in introducing plants having these marker-trait associations into a breeding population. This would allow for more efficient identification of molecular markers for agronomically and economically important traits.
Therefore, claim 1 remains rejected as obvious under Smith in view of Cockram, Ziolkowski and Shi.
With respect to claim 4 , Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches identifying new allelic variants (Smith, Abstract).
With respect to claim 5, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches the use of a statistical model that incorporates a genotype and a value of the phenotypic trait in the plant population to identify associations between genetic markers and phenotypic traits (Smith, Page 6, Paragraph 0020). This statistical model takes into account the genotype of the population for a set of genetic markers and the value of the phenotypic trait in that population and plants which have a marker-trait association are those where the marker genotypes and trait phenotypes are found together in the progeny of a plant or plants more often than if the marker genotypes and trait phenotypes segregated independently and therefore, Smith teaches that the marker-trait associations have increased statistical association as compared to the association in a control plant not comprising the allele for the trait of interest.
With respect to claim 7, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches a data set comprising phenotypic data (Smith, Page 6, Paragraph 0020).
With respect to claim 9, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, smith teaches nucleotide variation-phenotype associations through the association of genetic markers with a phenotypic trait where these markers can number up to 50,000 and be found throughout the whole genome (Smith, Page 6, Paragraph 0020; Smith, Page 21, Paragraph 0087, Last Sentence; Smith, Page 2, Paragraph 0006).
With respect to claims 11 and 12, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches positive and negative associations between a marker and a trait of interest; Smith teaches the use of TDT-based association tests to detect both positive and negative correlation between variables (Smith, Pages 50-51, Paragraph 0183). Specifically, Smith teaches the probability of transmitting an allele M1 (Marker 1) and not transmitting an allele M2 (Marker 2). Therefore, Smith teaches a positive association between a trait and the M1 allele and the negative association between a trait and the M2 allele and teaches ways to calculate the probability of each of these associations (Smith, Pages 50-51, Paragraph 0183).
With respect to claims 13 and 14, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claims 11-12 taught above (See above). Additionally, Smith teaches methods of calculating the probability of selecting plants having the positive association and not having the negative association (Smith, Pages 50-51, Paragraph 0183; Abstract). Smith also teaches selecting at least one of the members of the target plant population having a desired predicted value of the phenotypic trait (Smith, Page 6, Paragraph 0019).
With respect to claim 15, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches phenotypic data from inbred plants (Smith, Page 50, Paragraph 0181).
With respect to claims 21-22, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches that the target plant populations can comprise diploid plants and hybrid crop plants including F1 plants (Smith, Page 27, Paragraph 0102; Smith, Page 26, Paragraph 0099).
With respect to claim 43, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Smith teaches novel alleles of the genetic marker and therefore Smith teaches a novel marker trait association which in other words could be called a newly generated marker trait association (Smith, Page 29, Paragraph 0112).
With respect to claim 57, Smith in view of Cockram, Ziolkowski and Shi collectively teach all of the limitations of claim 1 (See above). Additionally, Ziolkowski teaches increased expression of HEI10 leads to increased crossing over and recombination (Ziolkowski, Page 306, Column 2, First Full Paragraph; Ziolkowski, Page 307, Column 1, First Full Paragraph). While Shi teaches the use of genome editing (CRISPR/Cas9 system) to introduce one or more genetic modifications comprising one or more additions in order to insert a constitutive promoter into the 5’ UTR of a gene of interest (Shi, Page 207, Abstract).
As noted above, at the time of filing it would have been obvious to the ordinary artisan to modify the method of Smith in order to conduct the marker association step in a population having increased recombination as described by Cockram through the overexpression of HEI10 by replacing the native HEI10 promoter with a constitutive promoter as taught in Ziolkowski and Shi respectively.
This would have been obvious because the method of Smith is drawn to mapping traits to genetic loci associated with identifiable markers and Cockram provides motivation to practice this type of method in plants having increased recombination rates because Cockram teaches that increasing recombination increases the accuracy of these types of methods. Further, Ziolkowski teaches that increasing expression of HEI10 leads to higher recombination rates and Shi teaches that using gene editing to swap promoters in a gene of interest with a constitutive promoter increases target gene expression.
Therefore, Smith teaches a base method, Cockram teaches a modification to the method that would improve the method by increasing accuracy, and Ziolkowski and Shi teach a method to increase HEI10 expression and recombination rate. These methods are all drawn to methods in the field of plant molecular biology related to plant and crop improvement.
The ordinary artisan would have been motivated to combine these methods because it would increase the accuracy and efficiency of methods for identifying molecular markers associated with important traits. This would allow for more efficient identification of molecular markers for agronomically and economically important traits.
Therefore, claims 1, 4-5, 7, 9, 11-15, 21-22, 43 and 57 remain rejected as obvious under Smith in view of Cockram, Ziolkowski and Shi.
Conclusion
All examined claims are rejected.
THIS ACTION IS MADE FINAL. 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN JAMES SULLIVAN whose telephone number is (571)272-0561. The examiner can normally be reached 7:30 to 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on (571)270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN JAMES SULLIVAN/ Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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