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 amendments and remarks, filed 02/27/2026, are acknowledged. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of Claims
Claims 1-14, 19, 27, 42, 43 are cancelled. Claims 45 and 46 are newly added.
Claims 18, 21, 23, 24, 32, 36, 41, 44 are withdrawn.
Claims 15-17, 20, 22, 25, 26, 28-31, 33-35, 37-40, 45, 46 are under examination.
Priority
This application claims the benefit of U.S. Provisional Application No. 63/704,757, filed October 8, 8,2024, U.S. Provisional Application No. 63/717,540, filed November 7,2024, U.S. Provisional Application No. 63/722,378, filed November 19, 2024, U.S. Provisional Application No. 63/736,437, filed December 19, 2024, and U.S. Provisional Application No. 63/769,928, filed March 11,2025.
Withdrawn Rejections
The rejection of claims 15-17, 20, 22, 25, 26, 28-31, 33-35, 37-40, 45, 46 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of applicant’s amendments.
Objections
The amendment includes two different newly added claims that are numbered as claim “45”. As such, these claims are objected to for being grammatically incorrect. Appropriate correction is required. For purposes of examination, the second claim 45 is referred to as claim 46.
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 15-17, 20, 22, 25, 26, 28-31, 33-35, 37-40, 45, 46 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 Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and ‘as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355).
Guidance Step 1: Under the broadest reasonable interpretation, the claimed invention (claim 15 being representative) is directed to a method of performing a process. Therefore, the claims fall into one of the four statutory categories. [Step 1: YES]
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. Regarding claim(s) 15, the following steps encompass an abstract idea:
(c) computer processing the aligned sequencing information reads using a gene-phenotype knowledge base…, wherein the computer processing comprises generating one or more vector embeddings of a corpus using a trained model, wherein the corpus comprises text documents relating to functional studies, case studies, or cohort studies, wherein the vector embeddings comprise one or more gene-phenotype associations, wherein the one or more gene-phenotype associations comprise one or more genetic variations of the text documents and one or more phenotypes of the text documents associated with the one or more genetic variations in the text documents;
(d) determining a pathogenicity of the prospective genetic variation by computer processing the prospective genetic variation and the phenotype identified in (c), wherein the pathogenicity is classified as benign, likely benign, likely pathogenic, pathogenic, or of uncertain significance;
(e) generating a set of pre-determined criteria for determining a likelihood of a clinical significance of the prospective genetic variation of the subject toward a phenotype of a disease based at least in part on: (i) the one or more vector embeddings comprising the one or more gene- phenotype associations,(ii) a frequency of the prospective genetic variation in a population having a phenotype of being affected by the disease, and(iii) a frequency of the prospective genetic variation in a population having a phenotype of being unaffected by the disease; and (f) generating a human interpretation of a clinical significance of the pathogenicity determined in (e), wherein the human interpretation comprises applying the set of pre-determined criteria to the determining in (d).
Mental Processes
With regards to said computer processing, 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 and analyzing sequence reads, and/or making decisions based on said analysis (i.e. associations). MPEP 2106.04(a)(2), section III.
With regards to said determining, 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 and analyzing data and/or making decisions based on said analysis. MPEP 2106.04(a)(2), section III.
With regards to said generating, these steps are recited at a high level of generality (without any technological details directed to how it is performed) and is not computer-implemented. As such, these steps encompass a mental process of analyzing data and/or making decisions based on said analysis (i.e. generating an opinion). MPEP 2106.04(a)(2), section III.
In addition, the Federal Circuit also treats analyzing information by mathematical algorithms, without more, as essentially mental processes within the abstract-idea category. Elec. Power Grp., supra, at 1354. For these reasons, the above steps fall within the “mental processes” grouping of abstract ideas because they cover concepts performed in the human mind, including observation, evaluation, judgment, and opinion. See MPEP 2106.04(a)(2), subsection III [Step 2A, Prong 1: YES].
Mathematical Concept
With regards to said computing, this step comprises generating vector embeddings and the artisan would recognize that generating vector embeddings (using a trained model) is the act of performing mathematical calculations and/or mathematically relating data. 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). Therefore, when read in light of applicant’s own specification, this limitation is directed to mathematical concept. See MPEP 2106.04 and 2106.05(II). [Step 2A, Prong 1: YES].
Natural Correlation
Under the broadest reasonable interpretation, the instant claims require using sequence information to identify genetic variation and phenotype. Therefore, the claimed invention amounts to identifying a naturally occurring relationship between data and disease (i.e. phenotype). See MPEP 2106.04(b). It is noted that even if a claim does recite a law of nature or natural phenomenon, it may still be eligible. For example, claims reciting a naturally occurring relationship between a patient’s genotype and the risk of QTc prolongation (a law of nature) were held eligible as not “directed to” that relationship because they also recited a step of treating the patient with an amount of a particular medication that was tailored to the patient’s genotype. Vanda Pharms., 887 F.3d at 1134-36, 126 USPQ2d at 1279-81. This particular treatment step applied the natural relationship in a manner that integrated it into a practical application. The court’s analysis in Vanda is equivalent to a finding of eligibility at Step 2A Prong Two (Pathway B).
B. Guidance Step 2A, Prong 2
Having made that determination, under the 2019 Guidance, the examiner next determines whether there are additional elements beyond the recited abstract idea(s) that integrate them into a practical application.
In this case, the additional steps/elements that are not part of the abstract idea are as follows:
(a) assaying deoxyribonucleic acid (DNA) molecules obtained or derived from a bodily sample of a subject to generate sequencing information sequencing reads, wherein the assaying comprises DNA sequencing;
(b) aligning the sequencing reads to a human reference genome to generate aligned sequencing reads;
With regards to assaying and aligning, these are physical steps that are recited at a high level of generality and result in gathering data for use by the abstract idea. Accordingly, these steps amount to insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g).
With regards to “using a…knowledge-base”, this feature is viewed as nothing more than a generic element representing data for use by the abstract idea and/or an attempt to generally link the use of the judicial exception to the technological environment of a computer. Moreover, generic computer components such as a database does not satisfy the inventive concept requirement. See MPEP 2106.05(f) and 2106.05(h). Notably, while the claim does recite “computer processing”, the claim does not include any specific machines or computer processor for practicing the claimed invention.
With regards to “using a trained model”, this additional element merely indicates a field of use or technological environment in which the judicial exception is performed. Although the additional element limits the identified judicial exception, this type of limitation merely confines the use of the abstract idea to a particular technological environment and thus fails to add an inventive concept to the claims. See MPEP 2106.05(h). Accordingly, the claims as a whole do not integrate the recited judicial exception into a practical application and the claims are directed to the judicial exception. [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. A review of applicant’s own specification teaches routine and conventional assays for generating sequence information, e.g. microarrays, qPCR, multiplex ligation-dependent probe amplification (MLPA), or a Sanger sequencing assay [0008, 0018]. Moreover, the additional element of “using the trained model” is at best mere instructions to “apply” the abstract ideas, which cannot provide an inventive concept. See MPEP 2106.05(f). 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].
Dependent Claims
Dependent claims 16, 17, 20, 22, 25, 26, 28-31, 33-35, 37-40, 45, 46 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. Claims 16-17, 20, 22, 25-31, 33-35, 37-40, 45, have further limit the specificity of the claimed assaying step, bodily samples, subject, and genetic variations, or the nature of the data being obtained. Accordingly, these claims are broadly interpreted as insignificant extra-solution activity for reasons set forth above (Step 2A, prong 2, and Step 2B analysis). Claims 27-31, 33-35, 37-40, 46, further limit the specificity of the abstract idea set forth above. Accordingly, these claims also encompass mental. Therefore, these claims are not indicative of an integration into a practical application. See also MPEP 2106.05(g).
Response to Arguments
Applicant’s arguments, filed 02/27/2026 have been fully considered but are not persuasive for the following reasons.
Applicant argues that the amended claims are patent eligible because they recite specific elements (namely said assaying, aligning, and generating vector embeddings) that are cannot be practically performed by the human mind. In response, the claimed assaying and aligning steps have not been interpreted as part of the abstract idea. Thus Applicant again appears to have a fundamental misunderstanding of the two-prong inquiry necessary for patentability. See the flowchart in MPEP § 2106, subsection III. Accordingly, applicant’s arguments regarding these two steps are not persuasive.
With regards to the computing step (comprising generating vector embeddings), the examiner maintains that this step is directed to an abstract that encompasses mental processes and mathematical concepts for reasons set forth above (Step 2A, prong 1). In addition, Applicant is reminded that the Office's eligibility guidance does not set limit on the number of calculations that can or cannot be performed mentally. MPEP § 2106.04(a)(2)III. Therefore, absent any evidence to the contrary, the examiner maintains that the claimed steps clearly encompass one or more abstract ideas and do not integrate the JE into a practical application.
Applicant additionally argues that the assaying, aligning, and computer processing steps recite a unconventional combination of steps. In response, applicant has not provided any evidence to support this assertion and no such evidence is apparent in the specification. It is additionally noted that the search for an inventive concept should not be confused with a novelty or non-obviousness determination. See MPEP 2106.05. In other words, it is true that claims can be free of the prior art and yet still rejected under 35 USC 101. That being said, the examiner maintains that steps c, d, e, and f are abstract for reasons set forth above (Step 2A analysis) and that the additional steps/elements of steps a and b do not qualify a ”significantly more” because the simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception for reasons set forth above and supported by prior art reference (Step 2B analysis). See also MPEP 2106.05 (II). Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps alone or in combination. See MPEP 2106.05(d)(Part II).
In summary, the claims result in generating a “human interpretation” and do not require using a processor. It is important to note that in order for a method claim to improve computer functionality, the broadest reasonable interpretation of the claim must be limited to computer implementation. MPEP 2106.05(a). Applicant has not provided any objective evidence of an improvement to the technology, nor does the specification explain the details of an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art. See MPEP 2106.04(d)(1) and MPEP 2106.05(a). As such, the claims do not recite an improvement to the technology or computer functionality. Therefore, absent any evidence to the contrary, the rejection is maintained.
Claim rejections - 35 USC § 112, 1st Paragraph
The following is a quotation of 35 U.S.C. 112(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.
This is a written description rejection.
Claims 15-17, 20, 22, 25, 26, 28-31, 33-35, 37-40, 45, 46 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. To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”). Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include: A) Partial structure; B) Physical and/or chemical properties; C) Functional characteristics; D) Known or disclosed correlation between structure and function; E) Method of making; and F) Combinations of A-E. See also MPEP 2163 and the 2011 Supplementary Guidelines to analysis under 35 USC 112 (Computer-Implemented Functional Claim Limitations).
Based on a consideration of the above factors, the level of skill and knowledge in the art, and the specification, the instant claims fail to meet the written description requirement for the following reasons:
Claim 15 is directed to a method of (a) assaying a bodily sample from a subject to generate sequencing information;(b) computer processing the sequencing information using a gene-phenotype knowledge base to identify a prospective genetic variation and a phenotype associated with the prospective genetic variation;(c) determining a pathogenicity of the prospective genetic variation, wherein determining the pathogenicity comprises computer processing the prospective genetic variation and the phenotype identified in (b); and(d) generating a human interpretation of a clinical significance of the pathogenicity determined in (c), wherein the human interpretation comprises applying a set of pre-determined criteria to the determining in (c).
In this case, under the BRI, the claimed invention purports to be able to determine the pathogenicity of all future genetic variations (i.e. the ability to produce a disease in a host) without imposing any boundaries on the type of genetic variants, sequences, or phenotype (i.e. disease). One of ordinary skill in the art would recognize that the claimed invention requires knowledge of specific sequence information associated with “prospective genetic variants” and diseases such that meaningful correlations can be made. However, the specification fails to disclose sufficient evidence that applicant had knowledge of correlations between specific genetic variations, phenotypes, and pathogenicity for the full scope of what is being claimed. Such information is not trivial. For example, Evans et al. (Genome Res. 2019. 29: 1144-1151), which teaches genetic variant pathogenicity prediction tools trained using disease-specific clinical sequencing data sets. In particular, unlike the instant claims, Evans focuses on patient variants from three disease panels: cardiomyopathy, epilepsy, and RASopathies (Fig. 1) and investigated the subset of epilepsy dominant genes: CDKL5, KCNQ2, KCNQ3, PCDH19, SCN1A, SCN1B, SCN2A, SCN8A, SLC2A1, SPTAN1, STXBP1, and TSC1. The instant specification is not associated with any specific gene-disease relationships. As best, the specification provides a generic discussion of databases comprising various types of data that can be utilized by the claimed invention [0095-0100] and a limited example associated with “cerebral palsy” [0202], which does not constitute an adequate written description of the broad subject matter of the claims. Therefore, the specification does not establish a reasonable structure-function correlation. “[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).
Response to Arguments
Applicant’s arguments, filed 02/27/2026 have been fully considered but are not persuasive for the following reasons.
Applicant generally argues that the claims no longer lack written description in view of the newly recited amendments. In response, this argument is not persuasive for reasons set forth above. In particular, while the claims now recite additional specificity with regards to the computational processing, the claims still are not limited to any particular type(s) of diseases and/or genetic variations. Accordingly, this rejection is maintained for the reasons set forth above.
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 15-17, 20, 22, 25, 26, 28-31, 33-35, 37-40, 45, 46 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) 15 is/are also rejected due to said dependency.
Claim 15 recites “…generating one or more vector embeddings of a corpus using a trained model”. Firstly, the artisan would recognize that a vector embedding is a numerical representation of data (e.g., words, sentences, images) in a continuous vector space and that a corpus is merely a large and structured set of texts used for training models. In other words, these are different limitations in terms of structure and function. Therefore, it is unclear what is meant by “vector embeddings of a corpus.” Clarification is requested via amendment.
Secondly, it unclear as to the metes and bounds of the claimed “training model” such that the artisan would recognize what internal structure of the claimed model is intended and in what way it has been “trained”. For example, the artisan would recognize that “training” a model generally requires feature selection, adjusting model parameters, optimizing loss functions, etc. However, the instant claims do not define the model in terms of parameters nor do they set forth any steps involved in the method/process of training. As such, it is also unclear in what way the generating step is “utilizing” the claimed model as the claims do not define the models in terms of parameters or variables nor do they set forth any steps involved in the method/process of use. Applicant is reminded that that terms such as “utilizing” or “using” do not amount to specific instructions showing in what information (or elements) are being used to achieve the intended results. A review of the specification does provide any limiting definitions that would serve to clarify this issue and it is improper to import narrowing limitations into the claims. MPEP 2111.01. In other words, applicant is claiming a generic black box model as a critical aspect of the invention (without defining it). As such, it is unclear what method/process applicant is intending to encompass, i.e. what parameters are associated with said models and in what way are they “used” to achieve the claimed function. Clarification is requested via amendment.
Cited Prior Art
The following prior art made of record and not relied upon is considered pertinent to applicant' s disclosure.
Hao et al. (Quantitative Biology. 2024;12:433–443) teaches methods for using LLMs in cellular modeling applications. In particular, Hao teaches vector embedding to represent objects such as text, images, genes, or amino acids using mathematical vectors in certain continuous space where the locations of the vectors represent meanings or semantics of the objects with regard to their relations.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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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