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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/14/2025 has been entered.
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Claims 28-41 and 44-56 are withdrawn as being drawn to a non-elected invention.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 examined on the merits.
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.
Claim Objections
Claim is newly 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.
Response to Applicant Arguments - 35 USC § 112 (Written Description)
Applicant’s arguments and amendments made 04/14/2025 are fully considered and not found to be persuasive.
Applicants arguments are drawn to the following concept:2015
Applicants argue that they have provided adequate description for the claims because the claims have been amended to limit the scope.
The independent claim has been limited to methods where “the population of plant is modified to have increased meiotic recombination by using genome editing to increase the copy number of HEI10, Msh4, Msh5, (SHOC1) XPF nuclease, or PTD in the one or more plants or to introduce one or more genetic modifications into a promoter region of the endogenous HEI10, Msh4, Msh5, SHORTAGE OF CROSSOVERS1 (SHOC1) XPF nuclease, or PARTING DANCERS (PTD) gene in the one or more plants to increase the expression level of the endogenous gene”.
Applicant argues that given the new limitations added to the claim, particularly given that these genes are known in the art that one skilled in the art would recognize from the disclosure that Applicant invented and had possession of the claimed subject matter.
These arguments are not found to be persuasive because while the target genes may be known in the art and may even be involved in promoting recombination, they simply recite broad approaches to modify plants and do not provide any substantial guidance linking the claimed sequences to the claimed phenotype.
Specifically no guidance is lacking with respect to the following:
Guidance on the structure function relationship between the broadly claimed genus of modifications in a promoter region of the five distinct claimed endogenous gene sequences and the function of increasing expression of those genes.
Guidance on the structure function relationship between the broadly claimed genus of increased expression of the claimed genes and the function of increased meiotic recombination.
Therefore, in addition to the limited guidance on which genes may affect recombination in which way, the applicants fail to adequately describe the full breadth of the scope of the claims such that the ordinary artisan would determine they were in possession of the full scope of the claimed invention. Therefore, applicant’s arguments are not found to be persuasive.
Claim Rejections - 35 USC § 112 – Written Description
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.
Due to Applicant’s amendment of the claims, the rejection is modified from the rejection as set forth in the Office action mailed 11/14/2024 as applied to claims 1, 4-5, 7, 9, 11-15, 21-22 and 43. Applicant’s arguments filed on 04/14/2025 have been fully considered but they are not persuasive, see above.
Claims 1, 4-5, 7, 9, 11-15, 21-22, 43 and 57 remain 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.
The Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id.
The claims are broad in the following aspects:
--claims 1, 4-5, 7, 9, 11-15, 21-22, 43 and 57 generically requiring the broad genus of either:
1. the introduction of a genome editing induced modification that increases the copy number of HEI10, Msh4, Msh5, SHOC1 XPF nuclease, or PTD or any modification, or
2. the introduction of any one or more genome editing induced modifications into the promoter regions of an endogenous HEI10, Msh4, Msh5, SHOC1 or PTD
where the modification(s) increases the expression level of the endogenous gene and meiotic recombination.
Initially, it should be noted that the claimed genus of the introduction of any mutation which increase the copy number of HEI10, Msh4, Msh5, SHOC1 XPF nuclease, or PTD gene is broader than it may appear. This is because the claimed genus includes extremely large insertions, including the insertion of whole transgenes other than the target HEI10, Msh4, Msh5, SHOC1 XPF nuclease, or PTD gene, and even whole gene deletions.
Additionally, it should be noted that the claimed genus of the introduction of any mutation into the promoter region of an endogenous HEI10, Msh4, Msh5, SHOC1 XPF nuclease, or PTD gene is broader than it may appear. This is because the claimed genus includes extremely large insertions, including the insertion of whole transgenes, whole gene deletions, replacement of promoters, frameshift mutations which result in extremely truncated proteins, and even silent mutations which do not result in any amino acid changes.
Meiotic recombination is an elaborate process involving many steps and is sensitive to cellular and environmental conditions, including external temperature, the location of the sister chromatids, and the synaptonemal complex, therefore the extremely large pool of mutations in the group of claimed genes is required to have a specific function of increasing expression of that gene and also increasing meiotic recombination.
Therefore this broadly claimed genus is required to modify a very complex process to produce a specific desired result.
In contrast, applicant provides only broad recitations of a method to increase meiotic recombination by introducing one or more nucleotide substitutions, additions and/or deletions in the plant’s genome to increase the activity of one or more genes that function to promote meiotic recombination (Instant specification, Page 13, First Paragraph).
Applicant also provides a non-limiting list of genes which may increase recombination when their expression is increased (Instant specification, Page 13, First Paragraph). However, nowhere in the examples do applicants show that increased expression of these genes is in any way linked to altered recombination rates (Emphasis added).
Applicant has not sufficiently described the necessary structural features that must be retained by the plant genome having an increased copy number of the target gene, such as genomic context of the newly inserted genes, nor has the applicant described the specific structures that must be modified/retained by the promoter regions in the target endogenous genes in order to produce the claimed increased expression of the target genes and to establish a structure-function relationship with respect to the specific function of increasing genetic recombination in a plant upon overexpression of the claimed genes.
It was known in the art at the time of filing that increasing wild type MSH4 may increase recombination rate (Crismani, Page 2, Lines 6-8) (Crismani, WO 2015181647 A1, December 2015).
Similarly, additional wild type HEI10 expression correlates with increased crossing over in Arabidopsis thaliana (Ziolkowski, Piotr A., et al. "Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination." Genes & development 31.3 (2017): 306-317.) (Ziolkowski, Page 311, Figure 4C-4E).
However, no guidance is provided by the applicant that links any of the other claimed genes to increased recombination rate, nor does applicant appear to provide any examples in which any modification increases copy number of the target gene or any modification whatsoever in the promoter region of any of claimed genes increases their expression and subsequently, increased recombination rate. In combination with the teachings of the art the ordinary artisan would not recognize that applicants were in possession of the broadly claimed invention.
In view of the lack of description from the state of art regarding the specific function, it should be noted that at the time of the instant invention was made, Applicant has not provided even that much description as discussed above (i.e. regarding the domain structures, subcellular localization, and biochemical activities).
Therefore, Applicants have not adequately described the structural features of such modifications that increase copy number or any modification whatsoever to the promoter region of one of the target genes that are required to be retained by members of the claimed genus as to establish a structure-function relationship between those structures and the function of increasing meiotic recombination. Without this relationship the ordinary artisan would be unable to distinguish members of the claimed genus from other chemical structures.
In fact applicants have not indicated any details about modifications which increase copy number of the claimed genes or to what degree expression must be altered in order to produce the claimed phenotype of increased meiotic recombination.
Thus, given the breadth of the claimed invention and the state of the art it appears that applicant would be required to provide extensive description in order to demonstrate a causal link between any level of increased expression of any of the target genes and increased meiotic combination and therefore demonstrate that the applicant was in possession of the broadly claimed invention.
The analysis will now turn to the second element of the court’s decision in Eli Lilly; namely, the description of a representative number of species.
Given the broad structural variable associated with any modification that increases copy number of the target gene or any modification whatsoever to the promoter regions of the target genes, the claims read on a broad and highly diverse structures and thus, in view of the analysis presented above, a skilled artisan would appreciate that the claimed genus of variant sequences is numerous and highly diverged and further that this large genus of variants are required to have the specific function of increasing recombination in a plant.
In contrast, Applicant does not appear to demonstrate any introduced modifications to endogenous genes that increase recombination rate. In view of the functional divergence between even the members sharing much more common features than the mere sequence identity, and the large size and structural diversity associated with the claimed genus, Applicant has not described a representative number of species for the claimed broad genus as a whole.
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Therefore, claims 1, 4-5, 7, 9, 11-15, 21-22, 43 and 57 remain rejected as lacking written description.
Response to Applicant Arguments - 35 USC § 103
Applicant’s arguments and amendments made 04/14/2025 have been fully considered but are not found to be persuasive.
Applicant’s arguments are summarized as follows:
Applicant has amended claim 1 to recite, “introducing the selected candidate plant into a breeding program” and none of the cited references teach this limitation.
Smith uses the adapted germplasm for marker-trait association analysis and incorporates the selected non-adapted germplasm having the marker-trait association into the adapted germplasm.
Neither Cockram, Ziolkowski nor Shi teach or suggest this use for the selected candidate plant.
Applicant’s arguments are not found to be persuasive because Smith teaches that the methods of Smith have a number of applications including in applied breeding programs in plants (Smith, Page 17, Paragraph 0074). Smith then provides an example of using the method of Smith in an applied breeding program in order to identify ideal plants for use as parents in one or more crosses (Smith, Pages 17-18, Paragraph 0074).
Therefore, applicant’s arguments that amending the independent claim to recite a step of introducing the selected candidate plant into a breeding program is not taught by any of the references are not persuasive because Smith does teach using the method of Smith to select candidate plants which are then used in a breeding program.
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 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).
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 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 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, 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.
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.
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, 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.
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.
/BRIAN JAMES SULLIVAN/ Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663