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 the Claims
Claims 1, 4-5, and 8-13 are pending and examined herein.
Claims 2-3 and 6-7 are canceled.
Priority
As detailed on the 08 April 2022 filing receipt, the application claims priority as early as 08 October 2019 to foreign patent JP 2019-185444. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Withdrawn Objections & Rejections
The objection based on the presence of browser-executable code is withdrawn in view of amendment to paragraph [2].
The interpretation under 35 USC 112(f) and related rejections are withdrawn as the filters are disclosed as algorithmic steps performed on a processor with the steps required being recited in the claim elements.
The rejection of claims 4-5 under 35 USC 112(b) are withdrawn in view of amendment clarifying similarity would be measured by on comparison to a threshold.
The rejection of claim 5 under 35 USC 112(b) is withdrawn in view of clarified antecedence of “the fusion gene.”
The rejection of claims 9-11 under 35 USC 112(b) is withdrawn in view of amendment clarifying the condition in which a pathogenicity score is higher.
The rejection under 35 USC 103 is withdrawn in view of the amendments and arguments, which recite the combination of at least ten filters for evaluating mutation data to score and rank pathogenicity of a mutation. Related art, such as Velculescu (US 20160273049 A1; previously cited on the 01 April 2022 IDS form) in view of Ganel (Bioinformatics 33(7): 1083-1085, 2017; previously cited on the 22 December 2025 PTO-892 form) and Yarham (Human Mutation 32(11): 1319-1325, 2011; previously cited on the 22 December 2025 PTO-892 form) teach some but not all of the required limitations, particularly the filtering steps, and further combination of additional filter is not clearly motivated by art. Therefore, the claims are considered free of the prior art. The provisional non-statutory double patenting rejection in view of copending application 18846165 is withdrawn for similar reasons.
The follow objections and/or rejections are either maintained or newly applied, and constitute the complete set of objections and/or rejections applied to the instant claims.
Specification
The disclosure is objected to because the paragraph numbering does not include the first paragraph. This objection remains from the previous office action.
Claim Interpretation
Claim 9 recites an “external apparatus” which is not disclosed in the specification. The specification discloses “an external server” (pg. 29, paragraph [102]). Therefore, the apparatus is interpreted as a server and thus a computer.
Claim Rejections - 35 USC § 112(b)
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 9-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 9 recites the limitation "a database filter" and “a function prediction filter”. There is unclear antecedent basis for these limitations because parent 1 also includes these terms, and it is unclear if the limitations in claim 9 are different than those in claim 1. Dependent claim 10 is rejected on similar grounds.
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, 4-5, and 8-13 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements individually and in combination, are directed to a judicial exception at Step 2A, Prong 2, and the additional elements of the claims, considered individually and in combination, do not provide significantly more at Step 2B than the abstract idea of ranking possibility a mutation is pathologic.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a computer system (claims 1, 4-5, and 8-11), a method (claim 12), and a non-transitory computer-readable medium (claim 13), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in the independent claims include determining a score and ranking a degree of possibility (claims 1 and 12-13). These steps are interpreted as numerical determinations and represent probability, which are mathematical concepts. A mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation (MPEP 2106.04(a)(2)).
Mental steps recited in claims and 12-13 include: determining if a mutation is in a database, which is a mental step of data comparison; determining if a mutation state affects protein coding, which is interpreted as determining amino acid translation and amino acid comparison, where comparison is a mental step; determining if a mutation is present in multiple species, where the step is interpreted as alignment and comparing amino acids at a given position; determining if a fusion gene is formed and whether the translation is sense or nonsense, where interpreting codons for continuity is a mental step of amino acid translation; determining if a fusion gene is functional is also based on its translation and is also a mental step; determining whether or not the mutation occurs in an enhancer region is a data evaluation step of determining the type and location of the mutation compared to a reference enhancer; and comparing to the time-series data is comparing two sequence for a change at a given position, and thus is data comparison and within the scope of what the human mind can perform,
Claims 4-8 recite additional information about determining the score, which is a mathematical concept as explained above.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
The independent claims recite additional elements that are not abstract idea, including an apparatus comprising a non-transitory computer readable medium and a processor (claim 1), receiving sequence information and outputting the created rank information (claims 1 and 12-13), storing information (claim 1), and a storage medium storing a program in a non-transitory manner (claim 13).
Claims 1, 9, and 12-13 recites an external apparatus, interpreted as a computer. The external apparatus is not recited in the preamble of claims 1, 9, or 13 as coupled with the apparatus or memory and thus is interpreted as outside the required apparatus.
The claims recite use of at least one general purpose computer including memory and receiving and/or storing information. The claims comprising computer components do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)). The specification discloses the output is to the control unit, which is interpreted as a computer or processor (pg. 6, paragraph [17]). The claim elements comprising storing records are mere instructions to apply an exception using a computer (MPEP 2106.05(f)) and insignificant extra solution activity (MPEP 2106.05(g)), and necessary data input and output do not integrate the abstract ideas into a practical application.
None of the dependent claims recite any additional non-abstract elements; they are all directed
to further aspects of the information being analyzed, the manner in which that analysis is performed, or
the mathematical operations performed on the information. [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
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 of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
The claims recite an apparatus comprising a non-transitory computer readable medium and a processor (claim 1), receiving sequence information and outputting the created rank information (claims 1 and 12-13) and a storage medium storing a program in a non-transitory manner (claim 13).
The claims recite at least one computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Receiving information, including over a network to/from an external computer, is a conventional computer function (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network). Finally, storage of sequence information in databases is disclosed as widely used (pg. 1, paragraph [2]).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 21 April 2026 Applicant Remarks
Applicant remarks recite certain steps cannot be performed mentally at Step 2A Prong One of 101 analysis, in particular steps such as (2a) identifying a genomic location of each nucleotide sequence obtained by dividing a mutant nucleotide sequence corresponding to a mutation state into a plurality of nucleotide sequences; (2b) determining whether the mutation state is a structural mutation spanning multiple genes by identifying the genomic location of the mutant nucleotide sequence corresponding to the mutation state; (2c) determining whether a fusion gene indicated by the mutation state represented by the mutant nucleotide sequence information is functional; (2d) determining whether the mutation contained in the mutant nucleotide sequence information is a structural mutation located near an enhancer registered in a memory unit; and (2e) determining whether the same mutation as the mutation contained in the mutant nucleotide sequence information is present in time-series information representing a mutation state extracted from the same individual as the sample at a time different from the time when the mutant nucleotide sequence information was extracted (pg. 12). These specific elements are asserted as allegedly not mental because: processing large genomic coordinate datasets spanning billions of base pairs, performing memory-based mapping of sequence fragments to reference genomes, evaluating frame continuity at genome junctions for fusion genes, comparing mutation states across multiple time points for the same individual, and accessing and querying databases of registered enhancers and gene positions are beyond mental capacity. This argument is not persuasive. Regarding (2a) and (2b), a mutant nucleotide sequence may be 1-2 positions long, and thus dividing it is trivial and can be performed mentally. Regarding (2c), determining if a gene is functional is interpreted as only requiring translating the codon for sense in the fusion, which can be performed mentally. Regarding (2d), determining if a mutation occurs in an enhancer region is a comparison based on alignment, which the human mind can perform. Regarding (2e), similar to (2d), this is an alignment-comparison step and thus also mental. It is noted that comparison across billions of base pairs in reference genome is not commensurate in scope with the claims. The claims require comparison of a position between species, genes, or time series, which does not require genomes but rather mutations at a single site whether it is a nucleotide or amino acid. Similarly, comparison of mutations at as few as one position is practically performed by the human mind, comparison to genomes is not recited in the claims in the structural determination steps and thus the assertion is not commensurate with the claims. Further, a reference genome is not required by the claims, only a plurality of registered genes on a single genome, which, under a broadest reasonable interpretation, reads on short, adjacent genes. The claims do not the limit the length of the genes, the distance between the genes, or the length of the mutation, which is interpreted as possibly being a single site. Accessing a database regarding the enhancer is agreed as an additional element, but comparison to an enhancer is similarly interpreted as a mental comparison.
Applicant remarks state the claims are not directed to math alone as they are tied to specific biological determinations (pg. 13, Section C). It is unclear what relationship this has to the finding of a mathematical concept within the claims. Iti s further agreed the claims do not recite economic practice or organizing human activity (pg. 143, Section D), though such an argument does not occur in a previous office action.
Applicant remarks state the processor is configured to apply rules to the sequence data and thus is a specific machine (pg. 14, Section A). However, the claims recite a processor which analyzes data. A processor of a system or apparatus is considered to read on a generic computer. A general purpose computer that applies a judicial exception, such as an abstract idea, by use of conventional computer functions does not qualify as a particular machine. Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709, 716-17, 112 USPQ2d 1750, 1755-56 (Fed. Cir. 2014). See also TLI Communications LLC v. AV Automotive LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (mere recitation of concrete or tangible components is not an inventive concept); Eon Corp. IP Holdings LLC v. AT&T Mobility LLC, 785 F.3d 616, 623, 114 USPQ2d 1711, 1715 (Fed. Cir. 2015) (noting that Alappat’s rationale that an otherwise ineligible algorithm or software could be made patent-eligible by merely adding a generic computer to the claim was superseded by the Supreme Court’s Bilski and Alice Corp. decisions) (see MPEP 2106.06(b)(I)).
The particular technological environment being genomic analysis (pg. 14, Sections C and D), for similar reasons, is not persuasive as a genomic analysis is not a technology. The recited technology is a general purpose computer and related data inputting/outputting, which are within the state of the art. The claims require data analysis steps which are abstract, implemented on a computer; the specific evaluations and rules do not graduate the steps from being abstract. The computer itself is not being improved as alleged (pg. 17, Section 4).
At Step 2A Prong Two, the alleged improvements (pg. 16-17) are derived from the data analysis steps, which are abstract, and so the analysis continues at Step 2B to determine if the additional elements provide significantly more, as an inventive concept cannot be furnished by abstract ideas (MPEP 2106.05). Applicant remarks state the filters are unconventional in combination (pg. 15, Section A), but the filters are interpreted as abstract, data analysis elements and not additional elements considered at Step 2B.
Therefore, the rejection is maintained under 35 USC 101.
It also noted that the remarks refer to eleven filters but there seem to be ten filters: (1) basic filter, (2) database filter, (3) function prediction filter, (4) conserved position filter, (5) frame filter, (6) pathogenicity filter, (7) structure filter, (8) functional fusion filter, (9) enhancer filter, and (10) time series filter.
Conclusion
The following art is made of record: Torkamani (WO 2015/148776 A1) teaches comparison of genomes at different time points (pg. 58, paragraph [206]).
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 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 final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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