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. Priority This application filed 10/27/2022 claims priority from Provisional Application 63294830 , filed 12/29/2021 , Provisional Application 63294828, filed 12/29/2021 , Provisional Application 63294827, filed 12/29/2021 , Provisional Application 63294820, filed 12/29/2021 , Provisional Application 63294816, filed 12/29/2021 , and Provisional Application 63294813, filed 12/29/2021 . The claims are therefore examined as filed on 12/29/2021 , the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s). Claim Status Claims 1-20 are pending. Claim 18 is objected to. Claims 1-20 are examined. Claims 1-20 are rejected. Information Disclosure Statement The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered. Claim Objections Claim 18 is objected to because of the following informalities: Claim 18 should instead recite “ …and a log probability of a corresponding reference amino acid less minus an entropy evaluated over amino acid-wise predictions.” (This appears to be the intended phrasing based on section [0170] of the specification) 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 an abstract idea of mental processes and mathematical concepts, without significantly more. The MPEP at MPEP 2106 sets forth steps for identifying eligible subject matter: (1) Are the claims directed to a process, machine, manufacture or composition of matter? (2A)(1) Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea? (2A)(2) Do the claims recite additional elements that integrate the judicial exception into a practical application? (2B) If the claims recite a judicial exception and do not integrate the judicial exception, do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception? With regard to step (1) ( Are the claims directed to a process, machine, manufacture or composition of matter? ): Yes. The claims are directed to one of the statutory classes. Claims 1-18 are directed to a process (computer - implemented method), claim 19 is directed to a product (a system with processors and memory ), and claim 20 is also directed to a product (a non-transitory computer readable storage medium ). With regard to step (2A)(1) ( Do the claims recite a judicially recognized exception?): Yes. The claims recite the abstract ideas of processing data using mental steps and mathematical concepts . Claims that recite nothing more than abstract ideas, natural phenomena, or laws of nature are not eligible for patent protection (see MPEP 2106.04). Abstract ideas include mathemati cal concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include but are not limited to: Applying a set of periodically-spaced masks to a first set of residues at a first set of positions in a multiple sequence alignment (mental process; the human mind is capable of masking data/replacing residues with a mask token in an alignment; claims 1, 19, 20) Cropping a portion of the multiple sequence alignment (mental process; the human mind is capable of cropping/rearranging data; claims 1, 19, 20) Generating a pathogenicity prediction for a variant based on the portion of the multiple alignment sequence (mental process/mathematical concept; the human mind is capable of generating a prediction based on data, determining a prediction from alignment data is equivalent to performing a calculation; claims 1, 19, 20) Aligning the query residue sequence to non-query residue sequences along a position dimension and along a per sequence dimension (mental process, the human mind is capable of aligning sequences by position and by sequence; claim 2-4) Shifting or positioning a cropping window (mental process; the human mind is capable of determining a window for cropping/selecting data; claims 10-13) Substituting the set of masks or residues with learning embeddings or position embeddings (mental process; the human mind is capable of substituting data; claims 14-15) Chunking the portion with learned mask embeddings, learned residue embeddings, and learned position embeddings into chunks (mental process; the human mind is capable of breaking data into chunks; claim 16) Processing the chunks as an aggregate and generating an alternative representation of the portion (mental process, the human mind is capable of processing a chunk of data as an aggregate and determining an alternative representation of data; claim 17) Generating the pathogenicity prediction based on a difference between a log probability of the variant and a log probability of a corresponding reference amino acid [minus] entropy (mental process/mathematical concept; the human mind is capable of predicting pathogenicity based on this calculation, and performing this calculation is a mathematical concept; claim 18) Dependent claims 5- 9 further limit the abstract ideas recited in the independent claims, and do not change their characterization as abstract ideas. Therefore, the claims recite elements that constitute one or more judicial exceptions. With regard to step (2A)(2) ( Do the claims recite additional elements that integrate the judicial exception into a practical application? ): No. Claim 1 and its dependents recite the additional element of the method being “computer-implemented”, claim 19 recites the additional element of a system comprising processors coupled to memory for performing the method, and claim 20 recites the additional element of a non-transitory computer readable storage medium with instructions for performing the method. The claims also recite the additional element of accessing a multiple sequence alignment to be used in analysis. While the claims recite the additional element of receiving /accessing data, such steps that only amount to necessary data gathering , without any technical details of how the data is obtained that integrate the judicial exception, are insignificant extrasolution activities that do not add a meaningful limitation to the claims (see MPEP 2106.05(g)). As a result, the judicial exception is not integrated into a practical application. In addition , w hile the claims recite additional elements related to the use of computers , they do not provide any specific details by which the computer, processor, or memory/computer readable medium performs or carries out the judicial exception listed in step (2A)(1), nor do they provide any details of how specific structures of the computer are used to implement these functions. The judicial exception is therefore not integrated into a practical application because the generically recited computer elements do not add a meaningful limitation to the abstract idea, as they amount to simply implementing the abstract idea on a computer (see MPEP 2106.05(f)) . Because the claims do not recite any additional elements that integrate the judicial exception into a practical application, the claims as a whole are directed to an abstract idea. With regard to step (2B) ( Do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception? ): No. The claims recite an abstract idea with additional elements; however, these additional elements are general computer elements added to abstract ideas, and non-particular instructions to apply the abstract idea by linking it to a field of use or extrasolution activity (see MPEP 2106.05(f-h)). General computer elements used to perform an abstract idea do not provide an inventive concept, and similarly, non-particular instructions to gather or access data do not provide an inventive concept. Non-particular instructions to gather or access data are also considered well-understood, routine and conventional activities (see MPEP 2106.05(d), which indicates that limitations such as “Receiving or transmitting data over a network” from Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 , “Storing and retrieving information in memory” from Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) ; OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 are recognized as conventional activities) . The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As a result, the claims as a whole do not provide an inventive concept. Claims Without an Art Rejection No art rejection is applied t o claims 1-20 . P rior art teaches machine learning methods of variant pathogenicity prediction (See EVANS 2019 , THUSBERG 2011, and WU 2021, cited on the 892) and masking/cropping of amino acid residues to improve multiple sequence alignment (see KUCK 2010 as cited on IDS filed 07-27-2023, and RAJAN 2012, cited on the 892), but does not teach the combined limitations of applying a set of periodically spaced masks to a set of residues containing the residue of interest in an alignment, cropping a portion of the alignment that includes the set of masks and a second set of non-masked residues, and using the cropped portion to generate a pathogenicity prediction. As such, no combinable art before the effective filing date could be found to render the claims as obvious. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure : EVANS 2019 “Genetic variant pathogenicity prediction trained using disease-specific clinical sequencing data sets” teaches a disease-specific ensemble classifier of pathogenicity based on regional constraint and variant-level features THUSBERG 2011 “ Performance of Mutation Pathogenicity Prediction Methods on Missense Variants” reviews several computational methods for the classification of SNPs according to their predicted pathogenicity WU 2021 “Improved pathogenicity prediction for rare human missense variants” teaches a computational system for assessing pathogenicity using a larger reservoir of training examples with uncertain accuracy and representativity RAJAN 2012 “A Method of Alignment Masking for Refining the Phylogenetic Signal of Multiple Sequence Alignments” teaches a method of alignment masking using clustering and elimination of noisy clusters Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT MARY C LEVERETT whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-5494 . 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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. /MARY C LEVERETT/ Examiner, Art Unit 1687