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 . Applicant’s preliminary amendment filed 7/19/2024 is acknowledged. Claims 3-5, 7-16 have been amended. Claims 1-16 are pending.
Applicant’s amendment to the specification filed 7/19/2024 is acknowledged and has been entered.
Priority
This application is a 371 of PCT/EP2023/051107 filed 01/18/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/19/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 7/19/2024. These drawings are found acceptable by the Examiner.
Claim Objections
Claims 2-16 are objected to because of the following informalities:
(a) Claims 2-16 are objected at the recitation of “A method according to claim”. It is suggested the claims by deleting “A” to --The--. Appropriate correction is required.
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 1-16 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.
(a) Claims 1-16 are indefinite in the claim 1 because the claimed method steps do not provide a clear nexus between the steps such that a clear interpretation cannot be ascertained. Specifically, it is unclear how determining the presence of at least one genetic variance of a plant pathogen and quantifying it by sequencing results in generating a resistance profile and /or virulence profile of the plant pathogen because merely performing sequencing alone does not necessarily result in generating such information. It cannot be determined how the resistance profile and/or virulence profile of the plant pathogen is generated. Clarification is required.
(b) Claim 11 is indefinite at the recitation of “preferably” because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
(c) Claim 14 is indefinite at the recitation of “SDHI” because abbreviations often have more than one meaning in the art. It is suggested inserting the full name of the abbreviation into the claim.
(d) Claim 15 is indefinite at the recitation of “DMI” because abbreviations often have more than one meaning in the art. It is suggested inserting the full name of the abbreviation in to the claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim analysis
Independent claim 1 is generally directed a method for determining a resistance and/or virulence profile for a plant pathogen in a location, the method comprising: receiving a sample comprising a plant pathogen, subjecting the sample to DNA sequencing, determining the presence of at least one genetic variance of the plant pathogen and quantifying said at least one genetic variance based on the DNA sequencing; and generating a resistance profile and/or virulence profile of the plant pathogen. The claims 2-16 embodies the limitations of the claim 1.
Step 1
For step 1 of the 101 analyses, the claims are found to be directed to a statutory category of a method.
Step 2A
For step 2A of the 101 analyses, the judicial exception of the claims are the steps of “determining the presence of at least one genetic variance of the plant pathogen” and “generating a resistance profile and/or virulence profile of the plant pathogen”. Additional limitations in dependent claims reciting “associating genetic variance...”, determining disease control…” , “comparing the resistance profile and/or virulence profile…”, and “recommending a resistant wheat variety and/or spray program…”. These steps are process that only collect/gather, or instructional steps that could be interpreted as mental analyses such as reading information on paper or computer screen or simply talking to a something, which encompasses mental analyses. The claims also comprise of steps of instructions for analysis of sequence data and appear to fall into the category of Mathematical Concepts, that is mathematical calculations to provide generic variances information. The Court has made clear if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract ideas cannot be circumvented by attempting to limit the use [the idea] to a particular technological environment. In the instant case, performing calculations such as to determine melt curve, normalize data, convert melting curve data to peaks or compare data by use of general computer technology are considered mere instructions to implement an abstract idea. The recitation of these steps in the method claims do not offer a meaningful limitation beyond generally linking “the use of the method to a particular technological environment,’ that is, implementation via computer for calculations or use of software and algorithms programs for gathering and analyzing data.” see Alice Corp v. CLS Bank Int’l 573 U.S. (2014).
This breadth does not impose a meaningful limit on the claim scope, such that all others are not precluded from using the natural principle of assessing the read data representative of any genetic variance of a plant pathogen and generating a resistance profile and/or virulence profile of the plant pathogen and no evidence is provided that any generic variance would be effective in providing any type of resistance or virulence information. The claims do not recite any steps beyond analysis in the judicial exception, and while sequence read data can be analyzed using a computer, the courts have also identified limitations that did not integrate a judicial exception into a practical application; for example, merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
Step 2B
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the analysis is applied. The claims comprise steps for receiving a sample and performing DNA sequencing, but these appear to be known conventional steps commonly known in related technical fields. For example, Liles et al (WO2016054222 teaching analyzing sample for plant pathogen using sequencing assay and detecting genetic variances (pages 25-28); and Campos et al (Horticulture Research, 8: 171, 1-12, August 2021) which teach analysis of genetic variances in plant pathogen using high throughput sequencing (see entire document). The additional limitations, which have been found to be known and routine in the art, do not transform the abstract idea into a patent eligible application of the abstract idea such that the claims amount to significantly more than the abstract idea.
The Court has made clear that to transform an unpatentable law of nature into patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words “apply it”. Essentially, appending conventional steps or elements, specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible. The Supreme Court also indicated that any additional steps that simply are routine and conventional in the art are insufficient to transform an otherwise patent-ineligible process.
In view of the foregoing, the claims are not drawn to patent eligible subject matter under 35 USC 101.
Claim Rejections - 35 USC § 102/103
13. 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.
14. 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.
15. 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.
16. Claim(s) 1-13 and 16 is/are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Marden et al (US 20150284796, October 2015).
Regarding claim 1-13 and 16, Marden et al teach the following: [0067] The present invention utilizes nucleic acid molecules collected from an individual plant or population of plants. In certain embodiments, the method utilizes nucleic acid molecules from different plants having known differences in phenotype (e.g. pathogen resistance). In one embodiment, the method utilizes nucleic acid molecules collected from one or more treated plants. Treated plants may be exposed to any suitable treatment, including for example, exposure to a pathogen, specific growing condition, temperature, humidity, soil, fertilizer, pesticide, and the like. In one embodiment, the treated plant is exposed to one or more compounds known or believed to increase expression of one or more defense response genes. Any type of nucleic acid molecule may be collected and used in the present invention.
[0068] The present method can be used to identify candidate genes that are likely involved in a trait of interest (e.g. pathogen resistance), in any suitable plant species. In certain instances, the method is used to identify candidate genes for slow-breeding plants for which traditional methods may be particularly unsuitable. Exemplary plants include, but are not limited to, varieties of woody food crop plants such as cacao, rubber, grape, citrus, apple, cherry, walnut, maple, oak, coffee, mango, papaya, pear, avocado, banana, walnut, pecan, pistachio, hazelnut, macadamia, apricot, peach, plum, grape, persimmon, mayhaw, and the like; varieties of woody fiber crops such as pine, poplar, cotton, and the like; and other crops such as corn, soy, wheat, rice, barley, hops, potato, melon, pineapple, tomato, tobacco, and the like. Such exemplary plants have too few generations per year for QTL and other breeding-based methods to provide rapid and relatively inexpensive results. Thus, the method presented herein may find application in any crop plant of interest.
[0069] In certain embodiments, the nucleic acid molecule is DNA, RNA, or a combination of DNA and RNA. In one embodiment, the nucleic acid molecule is mRNA. In certain embodiments, an entire transcriptome of the plant is collected. In certain embodiments, the method utilizes all or nearly all of the expressed genes (either in the form of DNA or RNA) to identify candidate genes, as described herein.
[0070] As contemplated herein, the present invention may be used in the analysis of any nucleic acid sample for which sequencing and analyses may be applied, as would be understood by those having ordinary skill in the art. For example, in certain embodiments, the nucleic acid can be, without limitation, genomic DNA, a subpopulation of DNA captured by annealing fragmented genomic DNA to well-designed probes matching coding regions only (exome sequencing), or targeted re-sequencing using PCR to amplify specific regions of genomic DNA. Other variations can include collection and analysis of mRNA. In one embodiment, reverse transcriptase is used to convert collected mRNA into DNA for subsequent analysis. In one embodiment, the mRNA is directly analyzed. In certain embodiments, DNA and/or RNA is obtained without a priori knowledge of its identity.
0072] In one embodiment, the method of the present invention uses the collected nucleic acid molecules, sequences it, assembles the transcriptome (i.e. constructs gene models of the coding regions of all genes expressed in the starting material), and uses bioinformatics, phylogenetics, gene polymorphism, and gene expression to organize the data, construct searchable databases, and obtain ranked lists of candidate genes containing potentially important polymorphism. In certain embodiments, traditional methods, such as PCR, cloning, long read sequencing of individual DNA molecules, and the like, can be used to characterize haplotypes at the candidate loci (i.e. fully characterize the potentially important gene variants).
[0073] In one embodiment, the method of the present invention comprises the building of databases and ranked lists of all protein coding gene regions containing variation most likely to affect the trait of interest (e.g. pathogen resistance). For example, in one embodiment, R genes and/or PR genes are identified that contain the most non-synonymous polymorphism relative to synonymous polymorphism (e.g. pN/pS or other measure of diversity in non-synonymous polymorphism or evolutionary rate of amino acid changes), an indicator of past and ongoing diversifying selection (i.e. evolutionary responses to diverse pathogens). In addition, if the starting material has been treated experimentally with pathogens or elicitors from pathogens, or comprises separate groups of susceptible versus resistant plants, ranked lists of genes most differently expressed or containing the non-synonymous allelic variants most strongly associated with resistance can readily be produced.
[0074] In certain embodiments, the method further comprises obtaining and analyzing microbial genes (e.g. bacterial, fungal, etc.) that may be associated with the plant. For example, the expression level and/or polymorphic analysis of microbial genes may be used to further refine a candidate list of plant genes, based on known or hypothesized interactions between the plant and microbial gene products.
[0075] FIG. 2 depicts a flow chart describing an exemplary method of the present invention.
[0076] As described above, in one embodiment, the nucleic acid molecules are isolated and collected from one or more tissues of interest of one or more plants of interest. Methods for isolating and collecting nucleic acid from a tissue sample are well known in the art.
[0077] In one embodiment, the collected nucleic acid is prepared for large scale sequencing. In certain embodiments, all of the expressed genes are used for analysis. In another embodiment, a subset of the expressed genes is used for analysis. For example, PCR amplification and further sequencing of particularly interesting genes, for example genes showing high differential expression or pN/pS, may be used to verify or extend results of a larger scale sequencing effort. Sequencing of the nucleic acid molecules may be performed using any methodology or sequencing platform known in the art.
[0078] The nucleic acid may be prepared (e.g., library preparation) for massively parallel sequencing in any manner as would be understood by those having ordinary skill in the art. While there are many variations of library preparation, the purpose is to construct nucleic acid fragments of a suitable size for a sequencing instrument and to modify the ends of the sample nucleic acid to work with the chemistry of a selected sequencing process. Depending on application, nucleic acid fragments may be generated having a length of about 100-1000 bases. It should be appreciated that the present invention can accommodate any nucleic acid fragment size range, including whole molecules, that is appropriate for a sequencer. In one embodiment, this is done by dividing the reads into segments and assigning the read segments into abutting (but not overlapping) regions of analysis. This can be achieved by capping the ends of the fragments with nucleic acid adapters. These adapters have multiple roles: first to allow attachment of the specimen strands to a substrate (bead or slide) and second have nucleic acid sequence that can be used to initiate the sequencing reaction (priming). In many cases, these adapters also contain unique sequences (bar-coding) that allow for identification of individual samples in a multiplexed run. The key component of this attachment process is that only one nucleic acid fragment is attached to a bead or location on a slide. This single fragment can then be amplified, such as by a PCR reaction, to generate hundreds of identical copies of itself in a clustered region (bead or slide location). These clusters of identical DNA form the product that is sequenced by any one of several next generation sequencing technologies.
At paragraph [0123] – [0124], [0123] The starting material for the process can be any living plant material from a sample of related plants in one or more populations of a species or variety of interest. The focal species used for these experiments are Beilschmiedia pendula, Brosimum alicastrum, Eugenia nesiotica, Lacmellea panamensis, Virola surinamensis, Dipteryx oleifera.
[0124] From beneath the canopy of five parent fruiting plants of each of these species, 15 post-dispersal seeds were collected. Cohorts of 15 seedlings per parent were grown in trays (one tray per parent plant per treatment) containing a common and well-mixed pool of sterilized soil obtained from within the forest. Three treatments were performed on this soil: a) control (sterile soil); b) soil inoculated 60 hrs. prior to harvest with a small quantity of live soil (an equal mix of subsamples collected from various locations in the forest); c) sterile soil soaked 48 hrs. Prior to harvest with the plant hormone salicylic acid (SA) (0.3 g of SA to 100 ml of distilled water per pot; volume of all pots were identical and weight approximately 1 kg. The purpose of these treatments was to stimulate changes in expression of genes that function in resistance to pathogens (present in live soil) and in response to the hormone (SA) that triggers the hypersensitive response. In the case of Beilschmiedia pendula, a high incidence of seed mortality caused by insect infestation reduced the abundance of live seeds to the point that two of the treatments (sterile soil; SA treated soil) were performed. After approximately one month of growth in a shade house, seedlings were uprooted, roots were washed free of soil, flash-frozen, then shipped for further analysis.
The preceding rejection is based on the judicial precedent following In re Fitzgerald, 205 USPQ 594 because the reference is silent with regards to the generating a resistant or virulence profile, However, the reference discuss bioinformatic and functional genomic approach to identify and rank genetic variance with potential function from a single generation of plants and further discuss building databases [0072] – [0073] The Burden is on Applicant to establish that the method of the prior art is different from that of the instant invention.
Conclusion
17. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY BENZION can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681
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