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 .
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Claims 1-8, 15-17, 20-23, 29-30, 33-34 remain withdrawn as being directed to a non-elected invention.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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9-14, 18-19, 31, 32 and 35 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 9 recites in part as follows:
“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”
However, the instant disclosure provides as follows:
“As used herein the terms "perturbation of expression of a gene" or "gene perturbation" are used interchangeably herein, and refer to the change in expression levels of a gene, when measured relative to a control or wild-type plant. In other examples, the plurality or population of plants used for the methods disclosed herein do not include any control or wild-type plants.”
It is unclear what “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” means. One possibility appears to be that perturbation means deviation from a wild-type plant, but the Specification explicitly states that the plant plurality may not contain any such wild-type plants (or controls). The other possibility is that the perturbation is relative to some other cluster. The issue is further confounded by the fact that the claims appear to explicitly contemplate embodiments wherein the cluster-specific gene is one that is introduced to the plants (See Claim 31). An introduced gene will inherently exhibit perturbed expression in all plants where it is exogenous, irrespective of any clustering – except if the gene is somehow subsequently lost during experimentation, which seems contrary to the purpose of the claimed process. As such, the metes and bounds of the claims are unclear. Given that the Specification allows for an absence of controls or wild-type plants in the plurality, the perturbation is reasonably interpreted to mean a perturbation in expression in one cluster versus at least one other cluster. Dependent claims are deemed indefinite by virtue of their dependency without resolving the cited deficiency.
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 9-13, 18-19, 31, 32 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. “Seed-Specific Expression of the Arabidopsis AtMAP18 Gene Increases both Lysine and Total Protein Content in Maize” PLOS One (November 18, 2015). This is a new rejection made upon further consideration of the claims and Applicant’s Remarks.
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;
(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 (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 a gene different than the at least one cluster-specific gene (Claim 10), 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, wherein it 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 (Claim 12), 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 9, wherein the cluster-specific gene is introduced into a plant, (Claim 31) 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.
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 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.
Chang teaches a method wherein a hybrid maize line “08×178” was transformed with an expression construct comprising an Arabidopsis thaliana AtMAP18 gene. (p. 3 ¶ 2). Chang teaches that the transformed plants were identified and that they all exhibited two new agricultural traits – increased lysine content and increased overall protein content – both important agronomic traits in maize. (p. 1, ¶ 1 – p. 2 ¶ 5, p. 6 ¶ 2-3). Chang teaches that transformants were subsequently divided into different lines and three such lines (or “clusters”) were selected for further experimentation. Each of the three clusters exhibited discreet but different levels of increase in protein accumulation rate and lysine accumulation rate and overall lysine accumulation (reading on at a second agronomic characteristic). (p. 7 ¶ 1 – p. 8 ¶ 3, Table 3). Chang teaches that the expression of the AtMAP18 gene in the different lines was measured using real-time PCR techniques and that the levels of two groups (FA9 and FA12) showed significant differences (increased expression) relative to the first group (FA7) which was normalized to 100% expression. (p. 6 ¶ 3, Figure 2). The three lines were then bred to create six subsequent generations, testing each generation to ensure that protein expression levels remained high. (p. 6 ¶ 2). Chang teaches that the results of agronomic analysis of the lines showed that AtMAP18 had the potential for commercial application in quality protein maize breeding. (p. 10 ¶ 5). Change teaches that expression of exogenous GhLRP, from cotton seed-specifically expressed it in maize increased the lysine content of transgenic maize seeds relative to the wild-type. (P. 2 ¶ 5).
Chang 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 Chang render the claimed inventions obvious.
It would have been prima facie obvious at the time of filing to modify the method of Chang 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 Change teaches that the results of agronomic analysis of the lines showed that AtMAP18 had the potential for commercial application in quality protein maize breeding. Because Chang showed that the lines improved protein content in hybrids made with T6 generation plants, one of ordinary skill in the art would have had a reasonable expectation of producing plants with improved protein and lysine content.
It would have been further obvious to modify the method of Chang such that the first agronomic trait is caused by perturbation of a gene that is different from the cluster-specific gene as required by Claim 10. One having ordinary skill in the art would have been motivated to do so because maize has numerous important nutrition-related agronomic traits that are controlled by genes endogenous to maize. Chang further teaches that expression of exogenous GhLRP, from cotton seed-specifically expressed it in maize increased the lysine content of transgenic maize seeds relative to the wild-type. As such, one of ordinary skill in the art would have been motivated to select a plurality of plants as a starting material that exhibits an altered trait related to nutrition such as increased lysine content that is caused by perturbation of an exogenous gene such as GhLRP, which increases lysine content significantly but not overall protein content as well, as is the case with AtMAP18.
Claim 12 recites “the method of claim 9, wherein it 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”. The control plants in Chang were the non-transformant “08×178” hybrid, which showed no expression of AtMAP18, while all three selected lines showed significant expression. (See Figure 1).
Claim 18 is properly rejected as being directed to further limitation of an alternatively listed limitation in rejected Claim 9.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. “Seed-Specific Expression of the Arabidopsis AtMAP18 Gene Increases both Lysine and Total Protein Content in Maize” PLOS One (November 18, 2015) in view of Bassel et al. (2011) Functional Network Construction in Arabidopsis Using Rule-Based Machine Learning on Large-Scale Data Sets (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 Chang as they are applied to Claims 9, 11-13, 18-19, 31, 32 and 35 are set forth previously herein.
Chang 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 Chang 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 teaches that machine learning algorithms can be used to analyze gene expression to determine relationships between different genes, and Chang teaches exactly such analyses performed by computation.
Response to Remarks
Applicant’s Remarks have been considered and deemed inapposite to the instant new 103 rejection, made upon further consideration of the claims.
Conclusion
No claims are allowed.
This action is NON-FINAL.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHARLES A LOGSDON whose telephone number is (571)270-0282. The examiner can normally be reached M-F 8:30 - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bratislav Stankovic can be reached at (571) 270-0305. 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.
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
Prosecution Insights