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 Claims
Claims 1-20 are under presently under examination.
Information Disclosure Statement
The five (5) information disclosure statement (IDS) document(s) submitted are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
Examiner Comment
Claim 1 is directed to a method, whereas claims 17 and 20 are directed to a system and computer readable medium, respectively. These claims are being examined together given that their functional limitations all rise and fall together. However, applicant is reminded that 37 CFR 1.142(a) provides that restriction is proper at any stage of prosecution up to final action. Ex parte Benke, 1904 C.D. 63, 108 O.G. 1588 (Comm' r Pat. 1904), e.g. in the event that the system and CRM claims are amended in the future to include additional structural and/or functional limitations that do not rise and fall with those of the method claims.
Priority
This Application claims the benefit of a plurality of U.S. Provisional Applications. However, 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), 120, 121 or 356 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 the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). In this case, all of the cited provisional applications (except for U.S. Provisional Application 63/351,283) fail provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. In particular, the Office is unable to find support for the for limitations directed to “burden testing”.
Accordingly, this application is granted the benefit of priority to U.S. Provisional Application 63/351,283, and the effective priority date for the instant application is June, 10, 2022.
Specification
The incorporation by reference in the specification to an unpublished U.S. application, foreign application or patent, or to a publication is improper. In this case, the instant specification seeks to “incorporates by reference” a number of different non-patent references and provisional applications that improperly incorporate essential subject matter (see at least pages 3-6). Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Claim Objections
Claims 1, 17, 20 are objected to because of the following informalities: The claims recite the term “including” after positive process limitations (e.g. “including: determining an optimal combination…”) and after sub-steps (e.g. “including: grid searching…”). This is confusing because it is unclear which of the claimed sub-steps are further limitations of the “determining” step and which of them are, in fact, additional positive process limitations (e.g. “selecting”). In other words, there is no logical flow to the claimed steps. In order to improve clarity, the examiner suggests amending the claims to include identifiers for all positive process steps, e.g. i), ii), iii), and different identifiers for the sub-steps (e.g. a), b), c), etc. Appropriate correction is required.
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 1-20 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.
The United States Patent and Trademark Office published revised guidance on the application of 35 U.S.C. § 101. USPTO’s 2019 Revised Patent Subject Matter Eligibility Guidance (“Guidance”). Under the Guidance, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes) (Guidance Step 2A, Prong 1); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)) (Guidance Step 2A, Prong 2).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that are not “well-understood, routine and conventional in the field” (see MPEP § 2106.05(d)); or 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50-57 (January 7, 2019).
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.(Guidance Step 2B). See Guidance, 84 Fed. Reg. at 54-56.
Guidance Step 1:
The instant invention (claim 1, 17, 20 being representative) is directed to a method, system and computer readable medium that performs a process. Thus, the claims are directed to one of the statutory categories of invention. MPEP 2106.03.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. In this case, the claimed steps that are part of the abstract idea are as follows:
determining an optimal combination of a maximum allele count and a minimum pathogenicity score threshold that maximizes significance of burden testing effects of rare pathogenic variants in a particular gene on a particular phenotype, including:
grid searching a plurality of allele counts and a plurality of pathogenicity score thresholds, including: (mental process)
generating a plurality of combinations of allele counts and pathogenicity score thresholds from the plurality of allele counts and the plurality of pathogenicity score thresholds; (mental process, mathematical concept)
identifying a plurality of groups of rare pathogenic variants corresponding to the plurality of combinations of allele counts and pathogenicity score thresholds; (mental process)
burden testing the plurality of groups of rare pathogenic variants in dependence upon a carrier status that separates carriers of a particular group of rare pathogenic variants in a cohort of individuals from non-carriers of the particular group of rare pathogenic variants in the cohort of individuals, (mental process)
determining a plurality of effect sizes and p- values corresponding to the plurality of combinations of allele counts and pathogenicity score thresholds; (mental process, mathematical concept)
selecting, from the plurality of combinations of allele counts and pathogenicity score thresholds, a particular combination of an allele count and a pathogenicity score threshold that has a most significant p-value; (mental process)
Mental Processes
With regards to grid searching, this step is recited at a high level of generality (without any technological details directed to how it is performed) and is not computer-implemented. As such, this step encompasses a mental process of observing data. MPEP 2106.04(a)(2), section III.
With regards to generating counts and thresholds, this step is recited at a high level of generality (without any technological details or rules directed to how it is performed) and is not computer-implemented. In addition, human brains routinely generate scores or thresholds. As such, this step encompasses a mental process of observing and analyzing the data. MPEP 2106.04(a)(2), section III.
With regards to identifying variants, burden testing, determining sizes and p-values, and selecting a particular combination, these steps are all recited at a high level of generality (without any technological details or rules directed to how they are performed) and are not computer-implemented. As such, these steps encompass a mental process of observing data, analyzing data and making a judgement based on said analysis. MPEP 2106.04(a)(2), section III.
Mathematical Concept
With regards to generating counts and scores, this step is recited at a high level of generality (without any technological details or rules directed to how it is performed) and is not computer-implemented. Moreover, generating numerical values amounts to mathematical calculations. As such, this step encompasses a mathematical concept of manipulating information through mathematical correlations or calculations. MPEP 2106.04(a)(2) Section I.
With regards to determining sizes and p-values, this step is recited at a high level of generality (without any technological details or rules directed to how it is performed) and is not computer-implemented. Moreover, determining numerical and statistical values amounts to mathematical calculations. As such, this step encompasses a mathematical concept of manipulating information through mathematical correlations or calculations. MPEP 2106.04(a)(2) Section I.
It is important to note that a mathematical concept need not be expressed in mathematical symbols, because “[w]ords used in a claim operating on data to solve a problem can serve the same purpose as a formula.” In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). See, e.g., SAP America, Inc. v. InvestPic, LLC, 898 F.3d 1161, 1163, 127 USPQ2d 1597, 1599 (Fed. Cir. 2018) (holding that claims to a ‘‘series of mathematical calculations based on selected information’’ are directed to abstract ideas). See also Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). The patentee in Digitech claimed methods of generating first and second data by taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form. The court explained that such claims were directed to an abstract idea because they described a process of organizing information through mathematical correlations, like Flook's method of calculating using a mathematical formula. 758 F.3d at 1350, 111 USPQ2d at 1721.
B. Guidance Step 2A, Prong 2
This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception or whether the claim is “directed to” the judicial exception. This evaluation is performed by (1) identifying whether there are any additional steps/elements recited in the claim beyond the judicial exception, and (2) evaluating those additional steps/elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. See MPEP 2106.04(d).
In this case, the additional steps/elements recited in the claim beyond the judicial exception are as follows:
using the particular combination as the optimal combination
With regards to said using, this step is recited at a high level of generality (without any technological details directed to how it is performed). As such, this step amounts to merely reciting the words “apply it” (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea. See MPEP § 2106.05(f).
With regards to the claimed processors and memory (claims 17, 20), these limitations are recited at high level of generality and read on a generic computer. Accordingly, these features are merely being used as tools to perform generic computer functions or the abstract idea, and therefore amount to no more than mere instructions to apply the exception using a generic computer. See MPEP 2106.05(f). Even when viewed in combination, these additional elements do not integrate the recited judicial exception into a practical application. [Step 2A, Prong 2: NO].
C. Guidance Step 2B:
This part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the recited exception i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05.
As discussed above, the non-abstract steps/elements amount to nothing more than insignificant extra-solution activity. Moreover, a review of the specification teaches a plurality of routine and conventional computational tools for performing the claimed invention [see at least 0044, 0149, 0207]. Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps. See MPEP 2106.05(d)(Part II). Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible. [Step 2B: NO].
D. Dependent Claims
Dependent claims 2-16, 18, 19 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. In particular, claims 2-16, 18, 19 are directed to limitations that further limit the specificity of the abstract idea or the nature of the data being used by the abstract idea. Accordingly, these claims are also directed to an abstract idea for the reasons set forth above (Step 2A, prong 1 analysis) and because data is abstract. Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more.
Claim rejections - 35 USC § 112, 1st paragraph
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1-20 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement is separate and distinct from the enablement requirement. The specification must: (1) describe the claimed invention in a manner understandable to a person of ordinary skill in the art, and (2) show that the inventor actually invented the claimed subject matter.
Regarding claim(s) 1, 17, 20 the specification fails to provide written description support for the following steps:
grid searching a plurality of allele counts and a plurality of pathogenicity score thresholds, including:
generating a plurality of combinations of allele counts and pathogenicity score thresholds from the plurality of allele counts and the plurality of pathogenicity score thresholds;
burden testing the plurality of groups of rare pathogenic variants in dependence upon a carrier status that separates carriers of a particular group of rare pathogenic variants in a cohort of individuals from non-carriers of the particular group of rare pathogenic variants in the cohort of individuals,
determining a plurality of effect sizes and p- values corresponding to the plurality of combinations of allele counts and pathogenicity score thresholds;
selecting, from the plurality of combinations of allele counts and pathogenicity score thresholds, a particular combination of an allele count and a pathogenicity score threshold that has a most significant p-value;
In this case, the above steps are not limited to any particular acts or operations and amount to functional language specifying desired results and/or specific functions. They are also not limited to any particular genetic variants or associated disease. They are not limited to any particular scores or threshold values associated with a particular pathogen or disease condition (such that an optimal combination can be determined). As a result, it is unclear in what way the claimed steps are being achieved given the breadth of what is being claimed. A review of the specification does not provide any specific details of how these steps are actually performed to achieve the claimed functions. The specification does not provide any specific algorithms, equations, or prose equivalent with regards to “grid searching” or “burden testing”. The specification does generically disclose “pathogenicity scores…generated by a convolutional neural network pathogenicity classifier such as PrimateAI-3D”; “…a wide range of additional AI, machine learning, and deep learning models are employed to generate a pathogenicity score” [0124]; and specific equations associated with statistical test calculations and weighted burden scores [Figure 1A, 1B, and 8]. However, in each case, these disclosures are insufficient as they do not provide any significant details with regards to how the instant claim limitations are actually being performed. Moreover, they are not commensurate in scope with what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As such, there is no evidence that applicant has actually disclosed the requisite functionality for the full scope of what is presently embraced by the claims.
Moreover, one of ordinary skill in the art would recognize that methods for selecting combinations of allele counts and pathogenicity cutoffs to optimize a rare-variant burden test for genes is not trivial.
Guo et al. (The American Journal of Human Genetics 103, 522–534; IDS filed 05/23/2023) teaches methods of burden testing of rare variants identified through exome sequencing. Unlike the instant claims, Guo teaches specific genes associated with a specific Mendelian disorder as well as specific QD scores and pairwise combinations of QD and SQSLOD scores [see entire].
Li et al. (The American Journal of Human Genetic, 2008, 83, 311–321) teaches methods for detecting associations with rare variants for common diseases. In particular, unlike the instant claims, Li teaches a well-defined genetic models that account for rare variant frequencies, genotype frequencies at variant sites, and penetrances [page 312-313]. However, there is no teaching with regards to determining a particular “combinations” of allele counts and pathogenicity scores.
Lin et al. (Scientific Reports, 2016, volume 6, Article number: 21824, pp.1-13) teaches methods for beyond rare-variant association testing. In particular, unlike the instant claims, Lin teaches a burden test based on a specific and well-defined backward-elimination algorithm for removing variants relative to other known statistical methods [see entire].
Lee et al. (The American Journal of Human Genetics, 2014, 95, pp.5–23) teaches a review of rare-variant association analysis methods. In particular, unlike the instant claims, Lee teaches specific and well-defined statistical models used for rare-variance testing [page 10-13]. Lee teaches that some of the methods requires p value calculations to counterbalance the effect of searching for the “optimal combination of statistics” conditional on the data [page 13]. However, there is no teaching with regards to determining a particular combination of allele counts and pathogenicity scores. In addition, Lee teaches that the analysis of rare variants is more challenging than that of common variants, e.g. due to the large sample size needed for simply observing a rare variant with a high probability and because standard single-variant association analysis is under-powered to detect rare-variant associations [page 9].
After careful consideration, the instant specification fails to disclose that applicant had knowledge of the specific computational methods to achieve the above functions for the full scope of what is being claimed. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number* of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69)(emphasis added). For the reasons discussed above, the specification does not satisfy the written description requirement with respect to the full scope of what is being claimed. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Claim rejections - 35 USC § 112, 2nd Paragraph
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 1-20 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 pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 1, 17, 20 is/are also rejected due to said dependency.
Claims 1, 17, 20 recite “grid searching a plurality of allele counts and a plurality of pathogenicity score thresholds”. In this case, it is unclear as to the metes and bounds of “grid search”. Neither the instant claims or the specification provide any limiting definition for this term that would serve to clarify the scope. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. The specification does generically disclose that “the grid search procedure described above requires correction for multiple-testing on generated false discovery rate-corrected p-values. In some implementations of the technology disclosed, multiple testing correction is performed using a Benjamini-Hochberg procedure” [0125]. However, such limitations are not commensurate in scope with what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. Moreover, the instant claims do not even introduce or define any type of “grid” that would serve to organize said counts or scoring thresholds, i.e. what is the nature of the grid, how is it being searched, and what is the result of said search. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 1, 17, 20 recite “generating a plurality of combinations of allele counts and pathogenicity score thresholds from the plurality of allele counts and the plurality of pathogenicity score thresholds.” Such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. The specification does generically disclose specific equations associated with statistical test calculations and weighted burden scores [Figure 1A, 1B, and 8]; “In some implementations…the pathogenicity scores are generated by a convolutional neural network pathogenicity classifier such as PrimateAI-3D. In other implementations…a wide range of additional AI, machine learning, and deep learning models are employed to generate a pathogenicity score” [0124] and generating “permutations of phenotype labels” [Figure 13]. However, in each case, such limitations are not commensurate in scope with what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement, as well as the nature of said “combinations”, e.g. linear combinations, permutations, coordinate combinations (on a grid for example), or otherwise. Clarification is requested via amendment.
Claims 1, 17, 20 recite “identifying a plurality of groups of rare pathogenic variants corresponding to the plurality of combinations of allele counts and pathogenicity score thresholds.” In this case, the term “rare” is a relative term and specification does not provide any limiting definitions, specific properties, or scoring criteria that would serve to clarify the scope, i.e. the result is subjective and imperceptible. As a result, it is unclear as to the metes and bounds of “rare pathogenic variants”. Clarification is requested via amendment.
Claims 1, 17, 20 recite “burden testing the plurality of groups of rare pathogenic variants in dependence upon a carrier status that separates carriers of a particular group of rare pathogenic variants in a cohort of individuals from non-carriers of the particular group of rare pathogenic variants in the cohort of individuals.” Such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. The specification does disclose specific equations associated with statistical test calculations and weighted burden scores [Figure 1A, 1B, and 8]. However, such limitations are not commensurate in scope with what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement, i.e. what operations are performed by said “burden testing” and in what way it is “in dependence” upon the carrier status. Clarification is requested via amendment.
Claims 1, 17, 20 recite “determining a plurality of effect sizes and p- values corresponding to the plurality of combinations of allele counts and pathogenicity score thresholds.” It is unclear what is meant by “effect sizes” such that the artisan would know how to avoid infringement. A review of the specification does not provide any limiting definition that would serve to clarify the scope. Clarification is requested via amendment.
Claims 1, 17, 20 recite “using the particular combination as the optimal combination”, which amounts to a “use claim”. Applicant is reminded that a claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q). In this case, the claim does set forth any steps involved in the method/process of use that would serve to clarify the scope of operations intended. As such, it is unclear as to who or what is actually “using” the combination as “the optimal combination”. Clarification is again requested via amendment.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
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