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 .
Claims 1, 3-12 and 16-17 are examined herein on the merits. Claims 13 and 15 remain as withdrawn to nonelected subject matter.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.
Claims 1, 3-12 and 16-17 remain rejected under 35 U.S.C. 103 as being unpatentable over Iaffaldano et al (2016 Industrial Crops and Products 89:356-362) in view of Wu et al (2013 Euphytica 192:131-143), further in view of Rickert et al (2003 Plant Biotechnology Journal 1:399-410).
The claims are drawn to methods for making artificial marker alleles, methods for determining the presence of a nucleic acid of interest, methods for selecting a nucleic acid of interest all comprising identifying at least one genomic locus which is genetically linked to a nucleic acid sequence of interest wherein the locus is highly conserved across different genotypes of the plant, introducing at least one insertion or deletion into said locus wherein the insertion or deletion is positioned outside of any coding regions of the nucleic acid of interest wherein the marker is inheritable to subsequent generations wherein the insertion or deletion is unique within the genome of the plant, wherein the insertion or deletion is positioned outside any splicing signal or regulatory element of the nucleic acid of interest, wherein the genomic locus is located at the 3’ end of the nucleic acid of interest wherein the insertion or deletion is between 1 and 60 contiguous basepairs and wherein the sequence is non-homologous to the genome of the organism wherein the insertion or deletion is introduced using CRISPR or zinc finger nucleases or TALENs or meganucleases, making the marker, detecting the marker and selecting for the presence of the marker and wherein the insertion or deletion is at least 10 contiguous base pairs and wherein the at least one InDel does not result in a loss of function of the at least one genomic locus.
Iaffaldano et al teach introducing via CRISPR/Cas insertions and deletions into dandelion to target and have a marker for the 1-FFT gene, wherein the deletions are between 2 and 22 contiguous bases wherein they are not homologous with the genome (see Figure 1 in particular) and insertions of 1 base into said DNA wherein the insertions and deletions are selected for inheritable markers(see materials and methods 2.6 and Figure 1B), wherein the insertions and deletions are inherently outside of regulatory regions and splicing signals and wherein the markers are inherently linked to the gene of interest since they reside within the gene of interest. Additionally, the gene in question is highly conserved across several species of plants. Iaffaldano et al further optimized the target sequence using CRISPRdirect which identifies the optimal site with balanced GC content.
Iaffaldano et al do not teach the above markers wherein the markers are outside the coding region of the gene of interest, wherein the markers are 3’ to the gene of interest or wherein the insertion is at least 10 contiguous base pairs, or wherein the markers expressly identify the genomic locus in a breeding process. Iaffaldano et al also do not teach wherein the InDel does not result in a loss of function in the at least one genomic locus.
Wu et al teach that Insertion Deletion markers are valuable for rice breeding, wherein the markers have size differences larger than 30 baser pairs (see abstract and InDel marker development) wherein both insertions and deletions are more than 10 base pairs (see above), wherein the markers are distributed across the genome wherein inherently some of the markers are outside the coding regions of the genes of interest and 3’ to coding regions. The express purpose of this generation of Indel markers was for linkage to genes of interest and several markers were scored with their proximity to known genes of interest and wherein said markers do not result in a loss of function (see page 140, Table 2 and Figure 2). Although Wu et al teach screening populations for existing insertion/deletion polymorphisms, it is clear that the principle for using the markers to screen for genes of interest is the same as that of the instant invention. Wu et al also expressly teach using said markers for identifying loci in a breeding process.
Rickert et al teach screening potato populations for Indel markers for the express purpose of using the Indel markers to select for and breed with genes of interest (see Figure 1 and pages 402-403). Rickert et al further teach wherein none of the BAC clones were identified by more than one of the probes indicating that the insertion or deletion is unique within the genome (see page 400 under Results as well as page 403 1st paragraph). Since Rickert performed large sections of sequencing with their InDel markers the locations could be determines and these markers could be used for genes of interest either upstream or downstream which would place them both 5’ and 3’ to the gene of interest (see pages 403-404 detailing sequencing).
Given the state of the art, the disclosures by Iaffaldano et al, Wu et al, and Rickert et al, it would have been obvious for one of ordinary skill in the art to generate insertion and deletion mutation markers as taught by Iaffaldano et al for use as markers as taught by all 3 references outside the coding region as taught by Wu et al and Rickert et al, and one of ordinary skill in the art would have been motivated to do so based on the need to generate more complete marker data sets for mapping and for selecting for disease resistance alleles as taught by Rickert et al.
It is noted that generating InDel mutations was known in the prior art, using InDel mutations near genes of interest for breeding purposes was known in the prior art both as evidenced above.
No claims are allowed.
Response to Arguments
Applicant's arguments filed 07/06/2026 have been fully considered but they are not persuasive.
Applicants urge that Iaffaldano does not teach introducing an InDel into a unique gene because there are multiple alleles of the gene in the organism being transformed (see pages 5-6 of Response filed on 07/06/2026).
This is not persuasive because the 1-FFT gene is a unique gene in the genome of dandelion and therefore a unique genomic target. The fact that multiple alleles are known to exist within different genomes of individuals in the species, does not mean that there are multiple repeats or copies within the same genome, absent evidence to the contrary.
Applicants urge that the technical approaches of the two references are different and that therefore one of skill in the art would not be motivated to combine the references.
This is not persuasive because the two elements both creating an artificial marker AND methods for screening for markers are known in the art and combining would have been obvious because the type of markers being screened for by the methods of Wu and Rickert are not dependent on the origin of the marker.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENT T PAGE whose telephone number is (571)272-5914. The examiner can normally be reached M-F 7-4 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached at 5712707058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENT T PAGE/Primary Examiner, Art Unit 1663
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