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 .
Supplemental Office Action
The following supplemental Office Action is being mailed to correct a clerical error in the previous Office Action mailed 06/26/2026. In particular, the previously mailed Office Action was erroneously for an entirely different application (18/170321). Accordingly, the instant Office Action corrects and replaces the previously mailed Office Action. As a courtesy, the time period for response is hereby reset as of the mailing date of this Office Action. The examiner apologizes for any inconvenience this has caused applicant.
Election/Restriction
Applicant's election with traverse of Group I (claims 1-18), Species A (claim 3), Species B (claim 7), and Species C (claim 13) in the reply filed on 05/18/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). Claim(s) 12, 13, 16, 18, 19, 20 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim.
Status of Claims
Claims 1-11, 14, 15, 17 are under examination.
Claims 12, 13, 16, 18, 19, 20 are withdrawn.
Priority
This application is a continuation of U.S. Application No. 15/974,976, filed May 9, 2018, which is a continuation application of U.S. Application No. 14/200,942, filed March 7, 2014 (now abandoned), which claims the benefit of U.S. Provisional Patent Application No. 61/782,240, filed March 14, 2013. Accordingly, the effectively filing date of the instant application is 05/09/2018.
Information Disclosure Statement
The information disclosure statement (IDS) document(s) submitted 08/01/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
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 1-11, 14, 15, 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and ‘as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355).
Guidance: Step 1.
Under the broadest reasonable interpretation, the claimed invention (claim 1 being representative) is directed to a method for performing a process and therefore falls within one of the four statutory categories.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. In this case, the following steps encompass an abstract idea for the reasons set forth below:
assigning measured values to the ensemble of sequencing reads;
calculating model-predicted values for the plurality of template polynucleotide strands utilizing a predictive model of nucleotide incorporations resulting from flows of nucleotide species according to a predetermined order;
modifying at least some model-predicted values using a first bias for forward strands and a second bias for reverse strands, wherein the modifying is based on variations between model-predicted values for different hypothesized sequences obtained using the predictive model of nucleotide incorporations resulting from the flows of nucleotide species according to the predetermined order;
calculating a measurement confidence value for each read in the ensemble of sequencing reads, wherein the measurement confidence value represents variations between the measured values and the modified model-predicted values;
identifying a plurality of reads in the ensemble as corresponding to a variant sequence based on the measurement confidence value.
Mental Processes
With regards to said assigning, this step is recited at a high level of generality (without any technological details directed to how it is performed) and does not explicitly require a computer. In addition, human brains routinely assign values. As such, this step encompasses a mental process of observing data and organizing information. MPEP 2106.04(a)(2), section III.
With regards to said modifying, calculating, and identifying, these steps are recited at a high level of generality (without any technological details directed to how they are performed or the structure of the predictive model) and do not explicitly require a computer. As such, these steps encompass a mental process of observing data, performing analysis, and making a judgement. MPEP 2106.04(a)(2), section III.
It is important to note 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, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016). [Step 2A, Prong 1: YES].
Mathematical Concept
With regards to said calculating, these steps require using a predictive model which is a mathematical construct for relating data and result in a mathematical calculation (confidence values). Accordingly, when read in light of the specification, these steps require a mathematical concept of manipulating information through mathematical correlations or calculations. MPEP 2106.04(a)(2) Section I. It is important to note that a mathematical concept need not be expressed in mathematical symbols, because “[w]ords used in a claim operating on data to solve a problem can serve the same purpose as a formula.” In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). See, e.g., SAP America, Inc. v. InvestPic, LLC, 898 F.3d 1161, 1163, 127 USPQ2d 1597, 1599 (Fed. Cir. 2018) (holding that claims to a ‘‘series of mathematical calculations based on selected information’’ are directed to abstract ideas). See also Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014)[Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
Having made that determination, under the 2019 Guidance, the examiner next determines whether there are additional elements beyond the recited abstract idea(s) that integrate them into a practical application. In this case, the additional steps/elements that are not part of the abstract idea are as follows:
receiving an ensemble of sequencing reads based on measurements obtained from a plurality of microwells of a sensor array, the measurements indicative of incorporation of nucleotide species into a plurality of template polynucleotide strands disposed in the plurality of microwells of the sensor array;
With regards to said receiving, this step is recited at a high level of generality and results in gathering data for use by the abstract idea. Accordingly, this step amounts to insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g).
With regards to the “utilizing a predictive model”, the model is recited at a high of generality without any details regarding structure or how it operates to achieve the claimed function. Accordingly, this provides nothing more than mere instructions to implement an abstract idea (presumably on a generic computer). See MPEP 2106.05(f). In addition, the claimed model also merely indicates a field of use or technological environment in which the judicial exception is performed. See MPEP 2106.05(h). As such, these additional elements fail to add an inventive concept to the claims.
In summary, the claimed invention does not provide any objective evidence of an improvement to the technology, nor does the specification explain the details of an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art. See MPEP 2106.04(d)(1) and MPEP 2106.05(a). Therefore, even when viewed in combination, these additional steps/elements do not integrate the recited judicial exception into a practical application. [Step 2A, Prong 2: NO].
C. Guidance Step 2B:
This part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the recited exception i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05.
As discussed above, the non-abstract steps/elements amount to nothing more than insignificant extra-solution activity. Moreover, applicant’s own specification teaches routine and conventional NGS sequencing technologies for obtaining (i.e. receiving) sequence read data that include sensors and arrays [0003]. In addition, Hubbell et al. (US20120264621) teaches a method for nucleic acid sequencing that includes a sensor array, microwells, and exposing the template polynucleotide strands to a series of flows of nucleotide species. Accordingly, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps. See MPEP 2106.05(d)(Part II). Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible. [Step 2B: NO].
Dependent Claims
Dependent claims 2-11, 14, 15, 17 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. Regarding claims 2-11, 14, 15, 17, these claims further limit the specificity of the abstract idea or the nature of the data being used and therefore are not patent eligible for reasons set forth above (Step 2A, prong 1). Therefore, the claims as a whole are not patent eligible.
Claim rejections - 35 USC § 112, 2nd Paragraph
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 1-11, 14, 15, 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 1 are also rejected due to said dependency.
Claim 1 recites “calculating model-predicted values for the plurality of template polynucleotide strands utilizing a predictive model of nucleotide incorporations resulting from flows of nucleotide species according to a predetermined order.”
This limitation is problematic for the following reasons. (1) It is unclear what is meant by the term “model-predicted values”, as the claimed model is not well-defined in terms of parameters nor does it correlate any values with sequence read information. A review of the specification does not provide any limiting definition that would serve to clarify the scope. Clarification is requested via amendment. (2) It is unclear as to the metes and bounds of said “a predictive model of nucleotide incorporations resulting from flows of nucleotide species according to a predetermined order” such that the artisan would recognize what structural limitation is intended. A review of the specification does not provide any limiting definition that would serve to clarify the scope, nor does it clarify the structural of the model or how it operates. Clarification is requested via amendment. (3) It is unclear what limiting effect is intended by the phrase “utilizing a predictive model of nucleotide incorporations resulting from flows of nucleotide species according to a predetermined order.” The method as claimed does not set forth any steps involved in the method/process of use of the claimed model. As such, it is unclear what method/process applicant is intending to encompass, i.e. what are “nucleotide incorporations resulting from flows of nucleotide species” are and in what way they are “utilized” by the model to achieve the claimed invention. Applicant is reminded that a claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q). Clarification is requested via amendment.
Claim 1 recites “modifying at least some model-predicted values…, wherein the modifying is based on variations between model-predicted values for different hypothesized sequences obtained using the predictive model of nucleotide incorporations resulting from the flows of nucleotide species according to the predetermined order.”
Firstly, it is unclear what limiting effect is intended by the phrase “hypothesized sequences”. A review of the specification does not provide any limiting definition that would serve to clarify the scope. Clarification is requested via amendment. Secondly, the modifying as claimed does not set forth any steps involved in the method/process of use of the claimed model. As such, it is unclear what method/process applicant is intending to encompass, i.e. what is the model and in what way is it the method “used” to achieve the claimed function. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q). Clarification is again requested via amendment.
Claim 11 recites “wherein the variance is estimated by decomposition of the variance in a flow and sequencing read into underlying latent components.” It is unclear what is meant by “decomposition of the variance in a flow and sequencing read into underlying latent components”. A review of the specification teaches a decomposition expression [0083]. However, examples are not limiting definitions and it is improper to import narrowing limitations into the claims. MPEP 2111.01. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment. In addition, it is unclear what structural or functional limitation is intended by the term “underlying latent components”. A review of the specification does not provide any limiting definition that would serve to clarify the scope. Clarification is requested via amendment.
Examiner' s Comment – Prior Art Rejection of Indefinite Claims
In view of the indefiniteness and lack of clarity in the instant claims, as set forth in the 35 USC 112(b) rejections above, the Examiner has had difficulty in properly interpreting instant claims. However, to avoid piecemeal prosecution and to give applicant a better appreciation for relevant prior art if the claims are redrafted to avoid the 35 USC 112(b) rejections, the following prior art made of record and not presently relied upon is considered pertinent to applicant' s disclosure. Applicant is reminded that prior art rejections under 35 U.S.C. 102 and/or 35 U.S.C. 103 may be applied in the next Office action in light of applicant's amendments, and that the next Office action can properly be made "Final" if these rejections are necessitated by amendment. See MPEP 706.07.
Lu et al. (Genomics Proteomics Bioinformatics, 2016, 14, pp.265–279) teaches methods for nanopore sequencing and genome assembly.
Zeng et al. (Nucleic Acids Research, Volume 41, Issue 13, 1 July 2013, pp.1-13) teaches a method for formulating homopolymer sequencing errors in Ion Torrent sequence data.
Poplin et al. (bioRxiv, Creating a universal SNP and small indel variant caller with deep neural networks, March 2018, pp.1-24), which teaches a deep convolutional neural network for calling genetic variations in aligned next-generation sequencing read data by learning statistical relationships (likelihoods).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
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