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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/07/2025 has been entered.
Status of the Claims
Claims 1-23, 29-35 are pending.
Claims 1-8, 15-17, 20-23, 29-30, 33-34 remain withdrawn as being directed to a non-elected invention.
Claims 9-14, 18-19, 31, 32 and 35 are examined herein.
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 9-10, 13, 18-19 and 35 remain rejected under 35 U.S.C. 103 as being unpatentable over Harper, et al. (Nature biotechnology 30.8 (2012): 798-802).
Applicant broadly claims a method of identifying at least one cluster specific gene from a plurality of plants, the method comprising the steps of:
(a) identifying at least one first cluster of plants and at least one second cluster of plants from the plurality of plants, wherein all plants in the plurality of plants exhibit an alteration in at least one first agronomic characteristic, wherein clustering is done on the basis of criteria selected from the group consisting of:
(i) alteration in at least one second agronomic characteristic in all the plants of a cluster;
(ii) similarity in gene expression profile between the plants of a cluster as determined by the distance metric with a cluster bootstrap confidence value of at least 50%;
(iii) perturbed expression of polypeptides from the same gene family in all plants from the same cluster;
(b) analyzing gene expression in plants from the at least one first cluster of plants and the at least one second cluster of plants;
(c) comparing the gene expression data from the at least one first cluster of plants to the gene expression data from the at least one second cluster of plants;
(d) identifying at least one cluster-specific gene that is perturbed in at least 80% of the plants from the at least one first cluster of plants, and perturbed in not more than 20% of the plants from the at least one second cluster of plants (Claim 9),
(e) selecting a plant that comprises the at least one cluster-specific gene identified in step (d); and
(f) using the selected plant in a plant breeding program.
the method of claim 9, wherein the alteration in the at least one first agronomic characteristic in each plant in the plurality of plants is due to perturbation of expression of a different gene than the at least one cluster-specific gene (Claim 10), the method of claim 9, wherein at least one of the steps of the method is done computationally (Claim 13), the method of claim 9, wherein the bootstrap confidence value for the plants in the same cluster is at least 60% (Claim 18), the method of claim 9, wherein the expression of the cluster specific gene identified in step (d) is perturbed in not more than 10% of the plants from the at least one second cluster of plants (Claim 19), the method of claim 12, wherein the selected cluster-specific gene is tested (Claim 35).
The limitation of claim 13, that at least one of the steps of the method is done computationally is reasonably interpreted to mean that one of the steps is done using any type of computation, including mental computations.
The limitation of Claim 35 that the selected cluster-specific gene is tested is reasonably interpreted to mean that the gene is analyzed in any way.
Harper et al. teaches a method of identifying genes responsible for plants traits using a combination of SNP markers and gene expression analysis in a genome-wide association study (GWAS). Harper et al. teaches that the crop plant Brassica napus was used in the study, a plant that exhibits alteration of traits relative to its progenitors, B. rapa and B. oleracea. Over 50 accessions of B. napus, representing five different crop groups were analyzed, each exhibiting different physiological and morphological traits. (p. 798 right col. ¶ 2 – p. 799 right col. ¶ 2). Harper et al. teaches that expression analysis between the groups was conducted computationally. (Online methods section). Among other analyses, Harper et al. teaches grouping the B. napus plants into plants exhibiting high (>50 μmol/g)- and low (<15 μmol/g) glucosinolate content. (reading on identifying at least one first cluster of plants and at least one second cluster of plants from the plurality of plants, wherein clustering is done on the basis of criteria selected from the group consisting of: (i) alteration in at least one second agronomic characteristic in all the plants of a cluster). Harper et al. teaches that low glucosinolate content correlated with low transcript abundance in transcripts of orthologs of glucosinolate biosynthesis genes. (p. 801 left col. ¶ 3-4). (Reading on analyzing gene expression in plants from the at least one first cluster of plants and the at least one second cluster of plants and comparing the gene expression data from the at least one first cluster of plants to the gene expression data from the at least one second cluster of plants). Harper teaches that PCR analysis following QTL mapping showed that the low glucosinolate accessions shared genome deletions that encompassed a transcription factor, an orthologue of the Arabidopsis HAG1. Harper et al. teaches that this gene is a transcription factor that controls the biosynthesis of aliphatic glucosinolates, which are the type preferentially accumulated in seeds, so deletion of its orthologs is consistent with being causative of a reduced seed glucosinolate phenotype in B. napus.(p. 801 left col. ¶ 4 – right col. ¶ 1). (Reading on identifying at least one cluster-specific gene that is perturbed in at least 80% of the plants from the at least one first cluster of plants, and perturbed in not more than 10% or 20% of the plants from the at least one second cluster of plants). It is reasonable to conclude that the agronomic characteristics (being at least one first agronomic characteristic) distinguishing B. napus from the progenitor plants is caused by genes that are different from the HAG1 gene or glucosinolate biosynthesis genes Harper et al. teaches that the method can be used to provide markers to accelerate breeding by marker-assisted selection. (Abstract).
Harper does not explicitly disclose that selecting a plant that comprises the at least one cluster-specific gene and using the selected plant in a plant breeding program as a single embodiment. However, the combined teachings of Harper render the claimed inventions obvious.
Harper teaches that low glucosinolate is one of the characteristics of high quality canola oil. (p. 799 right col. ¶ 3).
It would have been prima facie obvious at the time of filing to modify the method of Harper to include the step of selecting a plant that comprises the at least one cluster-specific gene and using the selected plant in a plant breeding program. One having ordinary skill in the art would have been motivated to do so because Harper teaches that low glucosinolate is one of the characteristics of high-quality canola oil and that the method can be used for marker-assisted selection. As such it would have been prima facie obvious to select a low glucosinolate line identified by the method for further breeding to make high quality crops.
Claim 18 is properly rejected as being directed to further limitation of an alternatively listed limitation in rejected Claim 9.
Because the expression of the HAG1 gene from the low glucosinolate accessions is entirely eliminated due to a deletion of the gene, it is reasonable to conclude that all of the low glucosinolate accessions exhibit perturbed expression and the high glucosinolate accessions exhibited at least some level of expression of the genes, not having the perturbation that is caused by the gene deletion. Because no degree of “perturbation” is specified, the limitation of Claim 9, part (d) and Claim 19 is deemed to be satisfied.
Response to Remarks
Applicant argues that Harper does not teach or suggest that the panel of Brassica napus does not contain any B. rapa and B. oleracea plants. As such, Applicant argues that the plurality of plants taught by Harper therefore does not satisfy the limitation that all plants in the plurality of plants exhibit an alteration in at least one first agronomic characteristic. (Remarks p. 8).
This is not found persuasive. The only requirement is that the plurality exists, and it can be a plurality of any types of plants and that there is an alteration in any agronomic characteristic relative to any other plant. Nothing in the Specification excludes Harper’s plurality. As set forth in the rejection, Harper’s plurality exhibits any number of alterations relative to B. rapa and B. oleracea plants. There is no requirement in the analysis that the plurality include B. rapa and B. oleracea plants. Applicant has chosen to claim this alteration in broad terms and the plurality of Harper satisfies the limitations of the claims.
Applicant argues that Harper does not teach identifying at least two different clusters of plants from the plurality based on a second characteristic. Applicant argues that Harper does not teach the hierarchical clustering process in Claim 9. (Remarks p. 8-9).
This is not found persuasive. Claim 9 recites no hierarchical clustering. MPEP 2111.01 provides that it is improper to read limitations into the claim from the Specification. The language of Claim 9 is set forth previously herein and how Harper teaches or renders obvious each step of the claimed process is set forth explicitly.
Applicant argues that instead of relying on the (allegedly deficient) teachings of Harper, Examiner has improperly relied upon the teachings of Applicant’s disclosure to arrive at the claimed invention. (Remarks p. 9-10).
This is not found persuasive. The rejection does not rely on Applicant’s disclosure. Instead the basis for the rejection as it relies on the teachings of the prior art are set forth explicitly herein.
Claims 11-12, 31 and 32 remain rejected under 35 U.S.C. 103 as being unpatentable over Harper, et al. (Nature biotechnology 30.8 (2012): 798-802), in view of Augustine, et al. (Plant Biotechnology Journal 11.7 (2013): 855-866), taken with evidence of Gigolashvili, et al. (2007, Plant J. 51, 247–261).
Applicant broadly claims a method of identifying at least one cluster specific gene from a plurality of plants, wherein all plants in the plurality of plants exhibit an alteration in at least one first agronomic characteristic, the method comprising the steps of:
(a) identifying at least one first cluster of plants and at least one second cluster of plants from the plurality of plants, wherein clustering is done on the basis of criteria selected from the group consisting of:
(i) alteration in at least one second agronomic characteristic in all the plants of a cluster;
(ii) similarity in gene expression profile between the plants of a cluster as determined by the distance metric with a cluster bootstrap confidence value of at least 50%;
(iii) perturbed expression of polypeptides from the same gene family in all plants from the same cluster;
(b) analyzing gene expression in plants from the at least one first cluster of plants and the at least one second cluster of plants;
(c) comparing the gene expression data from the at least one first cluster of plants to the gene expression data from the at least one second cluster of plants;
(d) identifying at least one cluster-specific gene that is perturbed in at least 80% of the plants from the at least one first cluster of plants, and perturbed in not more than 20% of the plants from the at least one second cluster of plants
(e) selecting a plant that exhibits perturbation of expression of the cluster- specific gene; and ---Internal Use---Application No.: 16/063311Confirmation No.: 5995 Docket No.: BB2512-US-PCT RESPONSE TO NON-FINAL OFFICE ACTION DATED NOVEMBER 24, 2020Page 4
(f) using the selected plant in a breedinq program. (Claim 9),
the method of claim 9, wherein the alteration in the at least one first agronomic characteristic in each plant in the plurality of plants is due to perturbation of expression of the same gene (Claim 11), the method of claim 9, further comprising the step of selecting a cluster-specific gene, wherein the cluster-specific gene confers upon a plant an alteration in the at least one first agronomic characteristic, wherein the plant shows a perturbation in expression of the cluster-specific gene when compared to a control plant (Claim 12), the method of claim 9, wherein the cluster-specific gene is introduced into a plant (Claim 31) the method of claim 31, wherein the wherein the cluster-specific gene is introduced into another plant using genome editing (Claim 32).
The limitation in Claim 31 “wherein the cluster-specific gene is introduced into a plant”, is reasonably interpreted to mean that the cluster-specific gene is introduced into any plant at any time either before or after the recited methods steps are performed.
Claim 32 recites “The method of claim 31, wherein the wherein the cluster-specific gene is introduced into another plant using genome editing.” Without further definition of “genome editing”, the claim is interpreted to mean that the gene is introduced using molecular biology techniques.
The teachings of Harper et al. as they are applied to Claims 9-10, 13, 18-19 and 35 are set forth previously herein.
Harper et al. does not teach that the alteration in the at least one first agronomic characteristic in each plant in the plurality of plants is due to perturbation of expression of the same gene, that the method further comprises the step of selecting a cluster-specific gene, wherein the cluster-specific gene confers upon a plant an alteration in the at least one first agronomic characteristic, wherein the plant shows a perturbation in expression of the cluster-specific gene when compared to a control plant or that the cluster-specific gene is introduced into another plant using genome editing.
Augustine, et al. (Plant Biotechnology Journal 11.7 (2013): 855-866) teaches a method of reducing expression of the MYB28 gene in Brassica juncea, a species closely related to B. napus, in seeds by targeted expression of suppression constructs that are introduced by molecular biology techniques into the plant genome. Gigolashvili, et al. (2007, Plant J. 51, 247–261) provides evidence that MYB28 and HAG1 are alternative names for the same gene. (Whole article). Augustine, et al. teaches that, as is the case with B. napus, low aliphatic glucosinolate content in seeds is a desirable trait, but that higher levels of aliphatic glucosinolates play major role as deterrents for herbivore attack as well as for the overall fitness of the plant. (p. 855 right col. ¶ 2 – p. 856, left col. ¶ 1, p. 862 left col. ¶ 2 – right col. ¶1). As such, the HAG1/Myb28 gene controls at least two different important agronomic traits in Brassica species. Augustine, et al. teaches that the suppression of MYB28/HAG1 caused a significant reduction in the accumulation of glucosinolates in seeds of B.juncea, and a reduction of aliphatic glucosinolates in leaves. (p. 859, right col. ¶ 4).
It would have been prima facie obvious to one of ordinary skill in the art to modify the method of Harper et al. such that the HAG1 gene is introduced for the purposes of co-suppression of expression of the HAG1 gene in B. napus, or alternatively to increase expression in tissues such that herbivore attack is minimized while maintaining low aliphatic glucosinolate levels in seeds. Plants could be grouped either way – the plurality being transgenic and more or less susceptible to attack then controls, or the plurality having high or low levels of seed glucosinolate relative to controls. The method of analysis as taught by Harper et al. could be readily applied in transgenic plants (potentially using the low- glucosinolate accessions taught by Harper et al. as starting material) to identify those plants with a desired or at least acceptable combination of low seed/high leaf glucosinolate levels. Indeed, while analyzing MYB28/HAG1, a transcription factor regulating numerous glucosinolate biosynthesis genes, would be an obvious first choice, Augustine, et al. teaches that said glucosinolate biosynthesis genes have been targeted for suppression in B. napus (p. 859, left col. ¶ 2), and as such, analyzing expression of any of these genes by the methods of Harper et al. would have been prima facie obvious. Selecting genes exhibiting perturbed expression in 80% plants of one group and no more than 10% or 20% of another group would be a reasonable and obvious step in view of the teachings of Harper et al. and Augustine, et al., which teach that elimination of the MYB28/HAG1 gene and suppression of the MYB28/HAG1 gene produces consistent and predictable effects on perturbation of gene expression.
Response to Remarks
Applicant argues that Harper does not teach or suggest that the panel of Brassica napus does not contain any B. rapa and B. oleracea plants. As such, Applicant argues that the plurality of plants taught by Harper therefore does not satisfy the limitation that all plants in the plurality of plants exhibit an alteration in at least one first agronomic characteristic. Applicant argues that Augustine and Gigolashvili do not cure the deficiencies of Harper. (Remarks p. 10-11).
This is not found persuasive. The only requirement is that the plurality exists, and it can be a plurality of any types of plants and that there is an alteration in any agronomic characteristic relative to any other plant. Nothing in the Specification excludes Harper’s plurality. As set forth in the rejection, Harper’s plurality exhibits any number of alterations relative to B. rapa and B. oleracea plants. There is no requirement in the analysis that the plurality include B. rapa and B. oleracea plants. Applicant has chosen to claim this alteration in broad terms and the plurality of Harper satisfies the limitations of the claims.
Applicant argues that Harper does not teach identifying at least two different clusters of plants from the plurality based on a second characteristic. Applicant argues that Harper does not teach the hierarchical clustering process in Claim 9. Applicant argues that Augustine and Gigolashvili do not cure the deficiencies of Harper. (Remarks p. 11).
This is not found persuasive. Claim 9 recites no hierarchical clustering. MPEP 2111.01 provides that it is improper to read limitations into the claim from the Specification. The language of Claim 9 is set forth previously herein and how Harper teaches or renders obvious each step of the claimed process is set forth explicitly.
Applicant argues that instead of relying on the (allegedly deficient) teachings of Harper, Examiner has improperly relied upon the teachings of Applicant’s disclosure to arrive at the claimed invention. (Remarks p. 11-12).
This is not found persuasive. The rejection does not rely on Applicant’s disclosure. Instead the basis for the rejection as it relies on the teachings of the prior art are set forth explicitly herein.
Claim 14 remains rejected under 35 U.S.C. 103 as being unpatentable over Harper, et al. (Nature biotechnology 30.8 (2012): 798-802) in view of Bassel et al. (The Plant Cell, Vol. 23: 3101–3116).
Applicant broadly claims a method of identifying at least one cluster specific gene from a plurality of plants, wherein all plants in the plurality of plants exhibit an alteration in at least one first agronomic characteristic, the method comprising the steps of:
(a) identifying at least one first cluster of plants and at least one second cluster of plants from the plurality of plants, wherein clustering is done on the basis of criteria selected from the group consisting of:
(i) alteration in at least one second agronomic characteristic in all the plants of a cluster;
(ii) similarity in gene expression profile between the plants of a cluster as determined by the distance metric with a cluster bootstrap confidence value of at least 50%;
(iii) perturbed expression of polypeptides from the same gene family in all plants from the same cluster;
(b) analyzing gene expression in plants from the at least one first cluster of plants and the at least one second cluster of plants;
(c) comparing the gene expression data from the at least one first cluster of plants to the gene expression data from the at least one second cluster of plants;
(d) identifying at least one cluster-specific gene that is perturbed in at least 80% of the plants from the at least one first cluster of plants, and perturbed in not more than 20% of the plants from the at least one second cluster of plants
(e) selecting a plant that exhibits perturbation of expression of the cluster- specific gene; and ---Internal Use---Application No.: 16/063311Confirmation No.: 5995 Docket No.: BB2512-US-PCT RESPONSE TO NON-FINAL OFFICE ACTION DATED NOVEMBER 24, 2020Page 4
(f) using the selected plant in a breedinq program. (Claim 9),
the method of claim 9, wherein at least one of the steps of the method is done by using a machine learning algorithm (Claim 14).
The teachings of Harper et al. as they are applied to Claims Claims 9-10, 13, 18-19 and 35 are set forth previously herein.
Harper et al. does not teach that one of the steps of the method is done by using a machine learning algorithm.
Bassel et al. teaches that machine learning algorithms can be used to analyze gene expression data in Arabidopsis thaliana and that such analysis can be used to discern the roles of genes in regulatory networks and make prediction about development, that machine learning algorithms can be used with any type of biological data (p. 3103 right col. ¶ 3 – p. 3113 lft col. ¶ 3).
It would have been prima facie obvious to one of ordinary skill in the art to modify the method of Harper et al. such that one of the steps of the method, such as analyzing gene expression, is done by using a machine learning algorithm. One having ordinary skill in the art would have been motivated to this because Bassel et al .teaches that machine learning algorithms can be used to analyze gene expression to determine relationships between different genes, and Harper et al. teaches exactly such analyses performed by computation.
Response to Remarks
Applicant argues that Harper does not teach or suggest that the panel of Brassica napus does not contain any B. rapa and B. oleracea plants. As such, Applicant argues that the plurality of plants taught by Harper therefore does not satisfy the limitation that all plants in the plurality of plants exhibit an alteration in at least one first agronomic characteristic. Applicant argues that Bassel does not cure the deficiencies of Harper. (Remarks p. 13-14).
This is not found persuasive. The only requirement is that the plurality exists, and it can be a plurality of any types of plants and that there is an alteration in any agronomic characteristic relative to any other plant. Nothing in the Specification excludes Harper’s plurality. As set forth in the rejection, Harper’s plurality exhibits any number of alterations relative to B. rapa and B. oleracea plants. There is no requirement in the analysis that the plurality include B. rapa and B. oleracea plants. Applicant has chosen to claim this alteration in broad terms and the plurality of Harper satisfies the limitations of the claims.
Applicant argues that Harper does not teach identifying at least two different clusters of plants from the plurality based on a second characteristic. Applicant argues that Harper does not teach the hierarchical clustering process in Claim 9. Applicant argues that Augustine and Gigolashvili do not cure the deficiencies of Harper. Applicant argues that Bassel does not cure the deficiencies of Harper. (Remarks p. 14).
This is not found persuasive. Claim 9 recites no hierarchical clustering. MPEP 2111.01 provides that it is improper to read limitations into the claim from the Specification. The language of Claim 9 is set forth previously herein and how Harper teaches or renders obvious each step of the claimed process is set forth explicitly.
Applicant argues that instead of relying on the (allegedly deficient) teachings of Harper, Examiner has improperly relied upon the teachings of Applicant’s disclosure to arrive at the claimed invention. Applicant argues that Bassel does not cure the deficiencies of Harper. (Remarks p. 15).
This is not found persuasive. The rejection does not rely on Applicant’s disclosure. Instead the basis for the rejection as it relies on the teachings of the prior art are set forth explicitly herein.
Conclusion
No claims are allowed.
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/CHARLES LOGSDON/Primary Examiner, Art Unit 1662