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 .
Claim Status
Claims 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 are currently pending and under examination herein.
Claims 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 are rejected.
Priority
The instant application claims the benefit of foreign priority to AU2018904348, filed 11/15/2018. The certified copies of papers required by 37 CFR 1.55 have not been received.
Applicant's claim for the benefit of a prior-filed application, PCT/AU2019/000141 filed 11/15/2019 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Accordingly, the effective filing date of the claimed invention is 11/15/2019.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/20/2026 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/20/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the list of cited references was considered in full by the examiner.
Withdrawn Rejections/Objections
Rejections and/or objections not reiterated from previous office actions are hereby
withdrawn in view of the Remarks filed 08/20/2026.
Regarding 35 U.S.C. 103, the claims are free of analogous art at least because the close art, as cited on the 892-form dated 08/28/2024, does not teach or fairly suggest a correlation between an intron metric and splice site abnormality.
The following rejections and/or objections are either maintained or newly applied. They constitute the complete set presently being applied to the instant application.
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 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 are rejected under 35 U.S.C. 101 because the claimed invention is directed to 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). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim(s) 1, 12, and 46 being representative) is directed to methods. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim(s) 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 recite the following steps which fall under the mathematical concepts, mental processes, and/or certain methods of organizing human activity groupings of abstract ideas:
Claim 1 recites determining the frequency at which the sequence occurs in a reference genome, expressed as a Native Intron Frequency of the first sample splice site sequence (NIFvar-1); wherein a NIFvar-1 of 0 (zero) indicates that the sample splice site is abnormal; the limitation determining a frequency is considered a mathematical calculation, as disclosed in present specification: “One measure of Native Intron Frequency is the number of times a particular nucleotide sequence appears in a splice site in a reference human genome sequence, which may be represented by NIFvar or NIF (count)” (paragraph [0068] [0111]). As such, said limitation falls within mathematical concepts groupings of abstract ideas.
Claim 2 recites the method is repeated with one or more sample splice site sequences comprised in the sample splice site; the limitation repeating is considered a mathematical calculation of repeatedly counting and calculating an event. The said limitation can also be practically performed in human mind (mental process) because human mind is able to repeatedly calculate the frequency of an event.
Claim 3 recites determining a measure of Native Intron Frequency of the first sample splice site sequence (NIFvar-1); the limitation determining frequency The limitation determining a frequency is considered a mathematical calculation. As such, said limitation falls within mathematical concepts groupings of abstract ideas (also mental process of counting and calculating frequency).
Claim 3 further recites determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref-1); the limitation determining frequency The limitation determining a frequency is considered a mathematical calculation. As such, said limitation falls within mathematical concepts groupings of abstract ideas (also mental process of counting and calculating frequency).
Claim 3 further recites determining a risk of abnormal splicing for the sample splice site by comparing NIFvar-1 with NIFref-1 against a Clinical Splice Predictor (CSP) reference database; the limitation determining a risk by comparing is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 4 recites determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref 1); the limitation determining a frequency is considered a mathematical calculation, and as such, said limitation falls within mathematical concepts groupings of abstract ideas (also mental process of counting and calculating frequency).
Claim 4 further recites determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref 1); the limitation determining a frequency is considered a mathematical calculation, and as such, said limitation falls within mathematical concepts groupings of abstract ideas (also mental process of counting and calculating frequency).
Claim 4 further recites determining a risk of abnormal splicing for the sample splice site by comparing NIFvar1 with NIFref 1 against a Clinical Splice Predictor (CSP) reference database; the limitation determining a risk by comparing is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 4 further recites that the determining steps are repeated with one or more sample splice site sequences; the limitation repeating is considered a mathematical calculation of repeatedly counting and calculating an event. The said limitation can also be particularly performed in human mind (mental process) because human mind is able to repeatedly calculate the frequency of an event.
Claim 4 further recites comparison of each further NIFvar with each corresponding NIFref against a CSP reference database; the limitation comparison of frequencies is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 5 recites determining a Percentile (NIFvar-i) of the first sample splice site sequence; the limitation determining a percentile is considered a mathematical calculation, and as such, falls withing mathematical concepts groupings of abstract ideas. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is capable of calculating a percentile.
Claim 5 further recites determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref-1); the limitation determining a frequency is considered a mathematical calculation, and as such, said limitation falls within mathematical concepts groupings of abstract ideas (also mental process of counting and calculating frequency).
Claim 5 further recites determining a Percentile (NIFref-1) of the first reference splice site sequence; the limitation determining a percentile is considered a mathematical calculation, and as such, falls withing mathematical concepts groupings of abstract ideas. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is capable of calculating a percentile.
Claim 5 further recites determining a risk of abnormal splicing for the sample splice site by comparing Percentile (NIFvar-1) with Percentile (NIFref-1) against a CSP reference database; the limitation determining a risk by comparing is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 6 recites determining a Percentile (NIFVar1) of the first sample splice site sequence; the limitation determining a percentile is considered a mathematical calculation (mathematical concept; also, a mental process).
Claim 6 further discloses determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref 1); the limitation determining a frequency is considered a mathematical calculation (mathematical concept; also, a mental process).
Claim 6 further discloses determining a Percentile (NIFref1) of the first reference splice site sequence; the limitation determining a percentile is considered a mathematical calculation (mathematical concept; also, a mental process).
Claim 6 further discloses determining a risk of abnormal splicing for the sample splice site by comparing Percentile (NIFvar1) with Percentile (NIFref1) against a CSP reference database; the limitation determining a risk by comparing is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 6 further discloses that the method steps (a) to (e) are repeated with one or more sample splice site sequences comprised in the sample splice site, wherein each sample splice site sequence comprises non-identical, consecutive nucleotides of the sample splice site; the determining steps are repeated with one or more sample splice site sequences; the limitation repeating is considered a mathematical calculation of repeatedly counting and calculating an event. The said limitation can also be particularly performed in human mind (mental process) because human mind is able to repeatedly calculate the frequency of an event.
Claim 6 further discloses comparison of each further Percentile (NIFvar) and each corresponding Percentile (NIFref) against a CSP reference database; the limitation comparison of percentiles is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 10 recites determining a clinical classification (s) associated with the nucleotide sequence of the first sample splice site sequence; the limitation determining a classification can be particularly performed in human mind (mental process), since human mind is able to categorize information in classes, for example abnormal splice site or benign variant splice site (specification [0007]).
Claim 10 further recites determining a risk of abnormal splicing for the sample splice site by assessing the clinical classification(s) associated with the nucleotide sequence of the first sample splice site sequence determined in step (c) against a CSP reference database. The limitation determining a risk by assessing classification can be particularly performed in human mind (mental process), since human mind is able to determine a risk based on an evaluation.
Claim 11 recites determining a clinical classification(s) associated with the nucleotide sequence of the first sample splice site sequence; the limitation determining a classification can be particularly performed in human mind (mental process), since human mind is able to categorize information in classes, for example “abnormal splice site or benign variant splice site” (specification [0007]).
Claim 11 further recites determining a risk of abnormal splicing for the sample splice site by assessing the clinical classification(s) associated with the nucleotide sequence of the first sample splice site sequence against a CSP reference database; the limitation determining a risk by assessing classification can be particularly performed in human mind (mental process), since human mind is able to determine a risk based on an evaluation.
Claim 11 further recites determining a risk of abnormal splice of the sample splice site by assessing the clinical classifications of each nucleotide sequence of each sample splice site sequence; the limitation determining a risk by assessing classification can be particularly performed in human mind (mental process), since human mind is able to determine a risk based on an evaluation.
Claim 12 recites determining a measure of Native Intron Frequency of the first sample splice site sequence (NIFvar-1) (mathematical concept of measuring a frequency).
Claim 12 further recites determining a Percentile (NIFvar 1) of the first sample splice site sequence and determining a Percentile (NIFref 1) of the first reference splice site sequence (mathematical concept of calculating a percentile).
Claim 12 further recites determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref-1); (mathematical concept of measuring a frequency).
Claim 12 further recites calculating a lower bound and an upper bound for Percentile (NIFvar-1) and calculating a lower bound and an upper bound for Percentile (NIFrefl); the limitation calculating a lower and upper bound is considered a mathematical calculation, as disclosed I n the present specification [0036] “suitable upper and lower bounds of a NIF or Percentile (NIF) may be calculated based on a percentage (eg, 10%, 5%, 2.5%, 2%) of a logarithmic distribution of NIF or Percentile (NIF), median NIF or Percentile median NIF, mean NIF or Percentile mean NIF”. As such, said limitation falls within the mathematical concepts groupings of abstract ideas. Also, the said limitation can be performed in human mind (mental process), since human mind is capable of performing said calculations.
Claim 12 further recites determining a range of NIF-shift by comparing the lower and upper bounds for NIFvar-1 with the lower and upper bounds for NIFref1 calculated; the limitation determining a range by comparison is considered a mathematical relationship of comparing values/numbers and as such falls within mathematical concepts groupings of abstract ideas. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to decide a range by comparing values.
Claim 12 further recites identifying unique variant(s) in the CSP database that create the identical nucleotide sequence of one or more sample splice sites from the subject (var-x); the limitation identifying variants can be particularly performed in human mind (mental process), since human mind is able to identify splice sequence appearing in a different splice site in one gene or two different genes.
Claim 12 further recites repeating determining and calculating steps to calculate the NIF-shift for all non-identical, consecutive nucleotide sequences of the sample splice site in the CSP database; the limitation repeating steps to calculate a shift is considered a mathematical relationship, as disclosed in present specification [0007] “the relative shift in frequency of a sample splice site, as determined by a comparison of frequency of a sample splice site with the frequency of the originating splice site”, and as sch, falls within mathematical concepts grouping of abstract ideas.
Claim 12 further recites determining a clinical classification(s) associated with each identical var-x nucleotide sequence in the sample splice site identified in the CSP database (mental process of putting data in different categories).
Claim 12 further recites determining the risk of abnormal splicing or likelihood of maintaining normal splicing for the sample splice site in the subject by assessing the clinical classification; the limitation determining a risk by assessing classification can be particularly performed in human mind (mental process), since human mind is able to determine a risk based on known information.
Claim 16 recites determining a clinical classification (s) associated with the nucleotide sequence of the first sample splice site sequence (mental process of putting data in different categories).
Claim 16 further recites determining a clinical classification(s) associated with the nucleotide sequence of the first reference splice site sequence; (mental process of putting data in different categories).
Claim 16 further recites comparing the NIFvar-I with the NIF ref-1 against a CSP reference database; (mathematical relationship (mathematical concept) of comparing values; also, mental process of comparing values)
Claim 16 further recites assessing the clinical classification(s) associated with the nucleotide sequence of the first sample splice site sequence and the clinical classification(s) associated with the nucleotide sequence of the first reference splice site sequence; the limitation assessing clinical classification can be particularly performed in human mind (mental process) since human mind is able to evaluate known information.
Claim 16 further recites assessing the clinical classification determined in classification determination step for each similar NIF-shift variant; the limitation assessing is a mental process of evaluating information and can be particularly performed in human mind.
Claim 18 recites determining a measure of Native Intron Frequency of the first sample splice site sequence (NIFvar-i) (mathematical calculation/mathematical concepts).
Claim 18 further recites determining a Percentile (NIFvar-1) of the first sample splice site sequence (mathematical calculation/mathematical concepts).
Claim 18 further recites determining a measure of Native Intron Frequency of a first reference splice site sequence (NIFref-1) (mathematical calculation/mathematical concepts).
Claim 18 further recites calculating a lower bound and an upper bound for Percentile (NIFvar-1) and calculating a lower bound and an upper bound for Percentile (NIFref-1); ); the limitation calculating a lower and upper bound is considered a mathematical calculation.
Claim 18 further recites determining a range of NIF-shift by comparing the lower and upper bounds for Percentile (NIFvar-1) with the lower and upper bounds for Percentile (NIFref-1) calculated in the calculating step; the limitation determining a range by comparison is considered a mathematical relationship of comparing values/numbers and as such falls within mathematical concepts groupings of abstract ideas. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to decide a range by comparing values.
Claim 18 further recites identifying unique variants in the CSP database that affect the same splice site as the sample splice site from the subject; the limitation identifying variants can be particularly performed in human mind (mental process), since human mind is able to identify splice sequence appearing in a different splice site in one gene or two different genes.
Claim 18 further recites repeating the determining and calculating steps to identify unique variants in the CSP database that affect the same splice site as the sample splice site that are calculated to have a similar NIF-Shift as determined in the range determination step; the limitation repeating steps can be particularly performed in human mind (mental process), since human mind is able to identify splice sequence appearing in a different splice site in one gene or two different genes by repeating some steps.
Claim 18 further recites determining the clinical classification(s) associated with each similar unique variant in the CSP database affecting the same splice site and the sample splice site from the test subject; the limitation determining a classification can be particularly performed in human mind (mental process), since human mind is able to categorize information in classes.
Claim 18 further recites determining the risk of abnormal splicing or likelihood of maintaining normal splicing for the sample splice site; the limitation determining a risk by comparing is considered a mathematical relationship of comparing values, as such, said limitation falls within mathematical concepts groupings of abstract ideas. See MPEP 2106.04(a)(2) I A. Also, the said limitation can be particularly performed in human mind (mental process), since human mind is able to compare known information. See MPEP 2106.04(a)(2) III A.
Claim 18 further recites assessing the clinical classification determined in step clinical determination classification step for each unique variant in the CSP database that affect the same splice site and are determined to have a similar NIF-shift variant identified in step the range determination step; the limitation assessing clinical classification can be particularly performed in human mind (mental process) since human mind is able to evolute known information.
Claim 21 provides further information.
Claim 23 provides further information.
Claim 29 provides further information.
Claim 31 recites he sample splice site is obtained by sequencing the splice site of a predetermined gene (further information).
Claim 46 recites generating a first abnormal splicing factor based on a measure of Native Intron Frequency (NIF) of the sample splice site (NIFvar-1) and a measure of NIF of a first reference splice site (NIFref_1); the limitation generating an abnormal splicing factor can be particularly performed in human mind (mental process), since human mind is able to generate/determine splicing factor based on known measurements, as disclosed in FIG. 13A/B.
Claim 46 further recites generating a second abnormal splicing factor by comparing the sample splice site sequence to pre-classified data wherein the pre-classified data includes splice site sequences which have been classified as an abnormal splice site or a benign variant splice site; the limitation generating by comparing is considered a mathematical relationship of comparing values and generating/determining based on the comparison, and as such, falls within mathematical concept groupings of abstract ideas. Also, the said limitation is the mental process of generating/determining based on a companion.
Claim 46 further recites generating a third abnormal splicing factor based on pre-classified splice site sequences having a similar NIFvaf-1 and a similar corresponding NIFrefl; the limitation generating an abnormal splicing factor can be particularly performed in human mind (mental process), since human mind is able to generate/determine splicing factor based on known measurements, as disclosed in FIG. 13A/B.
Claim 46 further recites generating a risk of abnormal splicing of the sample splice site by evaluating the first, second, and third abnormal splice factors; the limitation generating a risk by evaluating can be particularly performed in human mind (mental process), since human mind is able to determine a risk based on the result of an evolution.
Claim 56 provides further information.
Claim 57 recites determining a Percentile (NIFvar-1) of the first sample splice site sequence (mathematical calculation/mathematical concepts); determining a Percentile (NIFref-1) of the first reference splice site sequence (mathematical calculation/mathematical concepts); determining a risk of abnormal splicing for the sample splice site by comparing Percentile (NIFvar-1) with Percentile (NIFref-1) against a CSP reference database; wherein a Percentile (NIFvar-1) of 0 (zero) indicates that the sample splice site is abnormal (mathematical relationship/mathematical concepts; also, mental processes of comparing data to indicate a risk).
The identified claim limitations fall into one of the groups of abstract ideas of mathematical concepts, mental processes, and/or certain methods of organizing human activity for the following reasons. Therefore, claims 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 recite an abstract idea. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
The additional elements of claim(s) 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 include the following.
Claims 1, 12, 46, and 57 recite obtaining a first sample splice site sequence comprised in the sample splice site from the subject.
The additional elements of obtaining a sample from a subject only serves to collect the information for use by the abstract idea. Therefore, these additional elements amount to insignificant extra-solution activity, which is not sufficient to integrate the recited judicial exception into a practical application. See MPEP 2106.05(g).
MPEP 2106.04(d). I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a).
Applying or using a judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
In Step 2A, Prong 1 above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In Step 2B below, any remaining steps and/or elements are therefore in addition to the identified JE(s). Any such additional steps and additional elements are further discussed in Step 2B.
Here in Step 2A, Prong 2, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
At this point in examination, it is not yet the case that any of the Step 2A, Prong 2 considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of 1. an improvement, 2. treatment, 3. a particular machine or 4. a transformation is clear in the record.
Therefore, the additionally recited elements amount to insignificant extra-solution activity (See MPEP 2106.05(g)) and, as such, the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56 are directed to an abstract idea. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. An inventive concept cannot be furnished by an abstract idea itself. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
The additional elements of claim(s) 1-6, 10-12, 16, 18, 21, 23, 29, 31, 46 and 56-57 include the following.
Claims 1, 12, 46, and 57 recite obtaining a first sample splice site sequence comprised in the sample splice site from the subject.
The additional elements of obtaining a sample from a subject and obtaining amount to conventional methods for obtaining spice sites. This position is supported by Haque et al. (WO 2016209999 A1). Haque discloses a method of classifying splice site sequences and predict pathogenicity ([0034], [0036], [0045], [0049]) by obtaining test genetic sequence (obtaining a sample) using cost-effective DNA sequencing (abstract).
Therefore, the additional element is not sufficient to amount to significantly more than the judicial exception.
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
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. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Response to Arguments
Applicant's arguments filed 08/20/2026 have been fully considered but they are not persuasive. Applicant states (pg. 11-12)
NIF var-i =0 is a biophysical predictor of splicing pathogenicity and not a mere frequency calculation.
a) The claims use NIF vr.1=0 as a predictor of a physical biological
property of a genomic sequence: its splicing competency. Predicting binding strength of a splice site is a technical result and splicing competency is not an abstract idea. Turning input gene sequence data into a tangible output (NIF va-1) of the physical characteristics of a gene sequence (splicing functionality), is patent eligible under Step 2A.
(b) determining NIF va.1 transforms a sample splice site sequence - i.e., raw genetic sequence information - into a clinically-meaningful predictor of physical splicing properties and splicing pathogenicity that can inform clinical diagnoses and treatments.
This practical application - discussed further below - cannot be considered merely a mathematical correlation or abstract idea; it extends beyond a mere abstract idea or calculation.
These arguments are not yet persuasive. The Applicant remarks are directed to Step 2A Prong One of 101 analysis, specifically whether the claims recite a judicial exception.
With regards to argument a), instant claim 1 does not recite any predicting steps. Instead, instant claim 1 determines a frequency (abstract idea) and indicates a state/ abnormality based on a threshold (abstract idea). With regards to Applicant stating that the output is tangible, the output of identifying abnormal splice site is data, and data is not tangible.
With regards to argument b), for data (for example, sequence data in this instance), mere "manipulation of basic mathematical constructs [i.e.,] the paradigmatic ‘abstract idea,’" has not been deemed a transformation. CyberSource v. Retail Decisions, 654 F.3d 1366, 1372 n.2, 99 USPQ2d 1690, 1695 n.2 (Fed. Cir. 2011) (quoting In re Warmerdam, 33 F.3d 1354, 1355, 1360, 31 USPQ2d 1754, 1755, 1759 (Fed. Cir. 1994). See MPEP 2106.05(c).
Instant claims do not provide any details of how the frequency is determined. MPEP recognized that a claim to "collecting information, analyzing it, and displaying certain results of the collection and analysis," where the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, as an example of claims that recite mental processes. See MPEP 2106.04(a)(2) III.
Additionally, instant claims do not recite any steps pertaining to clinical diagnoses and treatments, as noted by the Applicant above, that could be analyzed as a relevant consideration for practical application.
Applicant states (pg. 11-12)
The claimed methods cannot be simplified to mentally-performable arithmetic steps.
The applicant maintains that this complex combination of operations represents a series of steps that are cross-dependent and rely upon genome-wide structures, precluding the methods from being mentally calculable by the human mind..
The claimed methods as a whole require the analysis of non-conventional thresholds and integration of vast quantities of genomic information in a manner that extends well beyond the types of mental processes contemplated by the judicial exception framework. The applicant therefore submits that the claimed invention as a whole is not directed to a judicial exception.
As stated above, the step of determining a frequency is a mathematical process. Applicant will further note that complexity of operations does not equate to eligibility. The fact remains that the steps are directed to operations that are mental and/or mathematical as above.
The instant claimed invention is directed to identifying abnormal splice sites in a sample of a subject by performing mathematical calculation of determining a frequency in data and identifying based on a threshold, which as states above, are considered judicial exceptions. Further, the identified claims recite a correlation between a DNA sequence of a subject and a risk identification. According to MPEP § 2106.04, subsection III., a judicial exception alone is not eligible subject matter, if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. The additional element of obtaining sample splice site sequence amounts to insignificant extra solution activity and do not integrate the recited judicial exceptions into a practical application.
Applicant states (pg. 13)
The combination of steps required by the claimed method, incorporate physical, technologically-implemented steps that yield clinically actionable outcomes… the invention enables robust clinical prediction of whether a splice site sequence is pathogenic or benign.
As supported by the Inventor Declaration provided herewith, the NIF thresholds defined in the claims allow human users, including those who may not be experts in the science of RNA splicing, to determine if a splice site is likely to be normal or abnormal. For example, clinicians treating patients that have genetic disorders resulting from splicing defects may use the claimed invention to assess sample splice site gene sequences, in turn directly impacting patient outcomes. Thus, the claimed invention, which inherently involves a combination of practical and technical steps, is not a generic process but a novel method with direct clinical and scientific application, particularly in the field of genetic disease.
These arguments are not yet persuasive. The Applicant remarks are directed to Step 2A Prong Two of 101 analysis, specifically whether the additional elements integrate the recited judicial exception into a practical application of the exception (emphasis added).
Again, instant claims do not recite any prediction steps. Even if recited, predicting is a judicial exception. A judicial exception that is not a generic (as stated by the Applicant above) judicial exception is still a judicial exception. A judicial exception alone is not eligible subject matter, if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See MPEP 2106.04 II. A. 2.
Moreover, instant claims do not recite any clinical outcomes to be analyzed.
Applicant states (pg. 14)
the claimed invention provides non-obvious, inventive features that distinguish the claimed invention from the elemental process of counting, grouping/categorizing, and assessing the simple prevalence of certain nucleotides.
NIF var1=0 is a novel, non-obvious concept that provides a technical contribution over the art which the applicant maintains amounts to significantly more than the judicial exception.
The claimed invention provides significantly more than existing, conventional processes, by solving a real-world problem in splice site prediction - strong, clinically-accurate prediction from gene sequence data alone - a recognized unmet need in clinical genomics and the field of RNA splicing.
These arguments are not yet persuasive. Applicant remarks are directed to Step 2A Prong Two, 1st consideration relating to an improvement over the previous state of the technology field integrating possible judicial exceptions into a practical application (MPEP 2106.04(d) and (d)(1)). However, it is not yet clear: (i) what is the particular improvement, (ii) that the improvement must be delivered by all embodiments within the claim scope and (iii) what is the nexus between the judicial exception, the improvement and a real world application. Applicant is invited to request an interview.
Step 2B of 101 analyzes additional elements to determine whether they amount to an inventive concept by considering them both individually and in combination to ensure that they amount to significantly more than the judicial exception itself.
Instant claims recite the additional element of obtaining sample splice site sequence, which is considered insignificant extra-solution activity. As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept. See MPEP 2106.05(g)(3).
Conclusion
No claims are allowed.
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/G.S./ Examiner, Art Unit 1686
/G. STEVEN VANNI/ Primary patents examiner, Art Unit 1686
