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 response filed 7/30/2026 has been fully considered. The following rejections
and/or objections are either reiterated or newly applied.
Status of Claims
Claims 1-4, 6-17, and 19-29 are pending and examined on the merits.
Claims 5 and 18 are canceled.
Claims 28-29 are newly added.
Priority
The instant application filed on 9/16/2022 claims the benefit of priority to U.S. Provisional Patent Application Nos. 63/294,813, 63/294,816, 63/294,820, 63/294,827, 63/294,828, and 63/294,830, all filed on 12/29/2021. Thus, the effective filing date of the claims is 12/29/2021.F
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Information Disclosure Statement
The 3 IDS forms filed on 6/11/2026, 9/10/2026, and 9/10/2026 have been entered and considered. Signed copies of each corresponding 1449 form have been included with this Office action.
Drawings
The drawings are objected to because the drawings do not comply with 37 CFR 1.84(u)(1). View numbers must be preceded by the exact abbreviation “FIG.”. Additionally, partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter (i.e. figure 4 should have its two views labeled as “FIG. 4A” and “FIG. 4B”).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because Figure 2 has nucleotide sequences that are 10 or more nucleotides and therefore require a sequence listing.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Interpretation
Claim 1 no longer invokes 35 USC 112(f) due to claim amendments filed on 7/30/2026.
Withdrawn Rejections
35 USC § 112(b)
The rejection of claims 1-27 under 35 USC 112(b) withdrawn in view of Applicant's claim amendments and remarks filed on 7/30/2026.
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.
The rejection of claims 1-4, 6-17, and 19-27 under 35 USC 101 contains newly recited portions necessitated by claim amendments, the rejection of claims 5 and 18 are moot due to being cancelled, and the rejection of claims 28-29 is newly recited.
Claims 1-4, 6-17, and 19-29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of a mental process, a mathematical concept, organizing human activity, or a law of nature or natural phenomenon without significantly more.
STEP 1: In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1).
STEP 2A PRONG 1: In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claims 1 and 28-29: “process [. . .] a first multiple sequence alignment that aligns a query sequence belonging to a target species with N non-query sequences belonging to N respective species having a first average evolutionary distance from the target species, the query sequence including a masked base at a target position that is flanked by right and left bases, to generate a first identity prediction of the masked base at the target position” and “process [. . .] a second multiple sequence alignment that aligns the query sequence belonging to the target species with M non-query sequences belonging to M respective species having a second average evolutionary distance from the target species, where M > N and the second average evolutionary distance exceeds the first average evolutionary distance, to generate a second identity prediction of the masked base at the target position” provides an evaluation (processing multiple sequence alignments (MSA) to predict a masked base) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“generate, utilizing an evolutionary conservation determination logic, a conservation score indicating a measure of evolutionary conservation of the masked base at the target position by comparing the first identity prediction [. . .] and the second identity prediction” provides a mathematical calculation (generating a score using a determination logic as exemplified in para.0078, 80, 81, or 83 of the instant specification involves calculating significant difference, probabilities, t-test statistics, etc.) that is considered a mathematical concept, which is an abstract idea. The limitation also provides an evaluation (comparing the predicted identities of the masked base) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claims 2-4, 6-17, and 19: each limitation of these claims further limits the mental process abstract idea (limits the MSA processing) of claim 1.
Claim 20: “the first identity prediction comprises a first probability distribution that specifies base-wise likelihoods of the masked base at the target position being adenine (A), cytosine (C), thymine (T), and guanine (G)” provides a mathematical calculation (predicting probabilities of potential identities of the masked base) that is considered a mathematical concept, which is an abstract idea.
Claim 21: “the first probability distribution further specifies base-wise likelihoods of the masked base at the target position being A, C, T, G, an unknown base (X), and a missing base (-)” further limits the mathematical concept abstract idea (predicting probabilities) of claim 20.
Claim 22: “the second identity prediction comprises a second probability distribution that specifies base-wise likelihoods of the masked base at the target position being A, C, T, G” provides a mathematical calculation (predicting probabilities of potential identities of the masked base) that is considered a mathematical concept, which is an abstract idea.
Claim 23: “the second probability distribution further specifies base-wise likelihoods of the masked base at the target position being A, C, T, G, -, and X” further limits the mathematical concept abstract idea (predicting probabilities) of claim 22.
Claim 24: “the first probability distribution and the second probability distribution are respective first and second softmax distributions” further limits the mathematical concept abstract idea (predicting probabilities) of claims 20 and 22.
Claim 25: “the evolutionary conservation determination logic applies t-test statistics to the first probability distribution and the second probability distribution to generate the conservation score indicating the measure of evolutionary conservation of the masked base at the target position” provides a mathematical calculation (generating a score using t-test statistics) that is considered a mathematical concept, which is an abstract idea.
Claims 26: “encode a background mutation probability estimation in the first identity prediction of the masked base at the target position” further limits the mental process abstract idea (including background mutation data as part of the MSA processing) of claim 1.
Claims 27: “encode a group-specific mutation probability estimation in the second identity prediction of the masked base at the target position” further limits the mental process abstract idea (including group-specific mutation data as part of the MSA processing) of claim 1.
These recitations are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or are mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Additionally, while claims 1 and 29 recite performing some aspects of the analysis on “A system, comprising: one or more processors; and a non-transitory computer-readable storage medium storing instructions” (claim 1) and “A non-transitory computer-readable storage medium storing instructions” (claim 29), there are no additional limitations that indicate that this requires anything other than carrying out the recited mental processes or mathematical concepts in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental processes” grouping of abstract ideas. As such, claims 1-4, 6-17, and 19-29 recite an abstract idea (Step 2A, Prong 1: YES).
STEP 2A PRONG 2: Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exceptions listed above are not integrated into a practical application because the claims do not recite an additional element or elements that reflects an improvement to technology. Specifically, the claims recite the following additional elements:
Claims 1 and 26-29: “utilizing a first machine-learning model”, “utilizing a second machine-learning model”, a “generated by the first machine-learning model”, and another “generated by the second machine learning model” (claims 1 and 28-29), “the first machine-learning model is further configured” (claim 26) and “the second machine-learning model is further configured” (claim 27) generally links the abstract idea to a particular technological environment (applying machine learning models) as per MPEP 2106.05(h)..
The machine learning steps of claims 1 and 26-29 are used to generally apply the abstract idea without placing any limitation on how the machine learning model operates. The claim omits any details as to how the machine learning solves a technical problem and instead recites only the idea of a solution or outcome. See MPEP 2106.05(f). Therefore, the limitation represents no more than mere instructions to implement the abstract idea of processing multiple sequence alignments, which is equivalent to adding the words “apply it” to the recited judicial exception. In addition, the claims confine the use of the recited judicial exception recited in claim 1 to the technological environment of machine learning by generally linking the use of the judicial exception to the recited machine learning model. Therefore, this general recitation does not integrate the judicial exception into a practical application. See MPEP 2106.05(h). Therefore, it can also be viewed as nothing more than an attempt to generally link the use of the judicial exception to a particular field of use or a technological environment. Furthermore, the limitations regarding implementing program instructions do not indicate that they require anything other than mere instructions to implement the abstract idea in a generic way or in a generic computing environment. As such, this limitation equates to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. Therefore, claims 1-4, 6-17, and 19-29 are directed to an abstract idea (Step 2A, Prong 2: NO).
STEP 2B: Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B).
As discussed above, there are no additional elements to indicate that the claimed “A system, comprising: one or more processors; and a non-transitory computer-readable storage medium storing instructions” (claim 1) and “A non-transitory computer-readable storage medium storing instructions” (claim 29) requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. Furthermore, no inventive concept is claimed by these limitations as they are well-understood, routine, and conventional: Regarding the above cited limitations in claims 1 and 26-27: Use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general-purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application or provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit).
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-4, 6-17, and 19-29 are not patent eligible.
Response to Arguments under 35 USC § 101
Applicant’s arguments filed 7/30/2025 are fully considered but they are not persuasive.
Applicant asserts that "the amended independent claim recites a specific computational architecture for improving machine learning-based determinations of evolutionary conservation for target species", the improvement rooted in a "dual machine-learning architecture [which] addresses the difficulty of detecting evolutionary conservation among closely related species without requiring the memory-consuming tree structures or branch links of existing approaches (Remarks 7/30/2026 pages 10-11). Applicant cites Ex Parte Wu (and its precedent Ex Parte Desjardins) as a basis for their argument (Remarks 7/30/2026 pages 11-15). Examiner notes the of change to MPEP regarding 35 USC 101 distributed on 12/5/2025 "explains how examiners should evaluate claims that recite improvements to technology, computer functionality, data structures, learning models, and other applied fields when conducting an eligibility analysis under 35 U.S.C. § 101, reaffirming that examiners consider the claimed invention as a whole when determining whether the claim integrates a judicial exception into a practical application." It is also noted that the improvement must be rooted in an additional element, and cannot simply come from the judicial exception(s) itself (i.e. one cannot argue for "a better algorithm" etc.). Examiner notes that Applicant even specifically cites their own specification to this end, and recites "'improved algorithms for detecting conservation at short evolutionary distance,' including deep-learning models capable of detection conservation over such [short] timescales" (Remarks 7/30/2026 page 12). Because the only additional elements (identified in claims 1 and 26-29) involve merely "utilizing" machine-learning models which only serve to generally link the abstract idea to the technological environment of machine learning, these elements merely provide insignificant extra-solution activities that do not serve to integrate the judicial exceptions into a practical application. Furthermore, Applicant repeatedly refers to amended claim 1 expressly reciting "the computational, dual machine-learning architecture used to provide these improvements" and goes on to recite the first two limitations of amended claim 1 and argues that the recited limitations together solve the technical problem identified in the instant specification (Remarks 7/30/2026 pages 13-14). Examiner notes that these amended limitations are not detailing any specific machine-learning "architecture", and are simply stating that two different machine-learning models (again, the architecture of which is not recited) are processing a particular type of multiple sequence alignment data (the processing of which may be performed in the human mind and is therefore considered a mental process, which is an abstract idea). Finally, section "B" of Applicant's Remarks on pages 14-15 reiterate the argument that amended claim 1 and new claims 28-29 integrate any abstract idea into a practical application. Examiner notes the response in the paragraph immediately above.
Therefore, the rejection of claims 1-4, 6-17, and 19-27 under 35 USC 101 is maintained, and the rejection of claims 28-29 is newly recited.
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 TH REE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this finaI action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert A. Player whose telephone number is (571)272-6350. The examiner can normally be reached Mon-Fri, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs can be reached on 571-270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.A.P./Examiner, Art Unit 1686
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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