DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election without traverse of Group I, comprising claims 1-13 in the reply filed on 04/21/2026 is acknowledged.
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/21/2026.
Claims Status
Claim 15 is canceled.
Claim 21 is new, and is dependent upon the non-elected invention of claim 14.
Claims 1-14 and 16-21 are pending.
Claims 14 and 16-21 are withdrawn from consideration.
Claims 1-13 are examined on the merits.
Priority
The instant application is a continuation of Application No. 16/364,336, filed 03/26/2019 (now Patent 11,453,912), which is a continuation of Application No. 13/967,665, filed 08/15/2013 (now Patent 10,273,540), which claims priority to provisional application No. 61/775,322, filed 03/08/2013, Application No. 13/967,665 is a continuation in part of Application No. 13/283, 320, filed 10/27/2011 (now Patent 8,666,678), which claims priority to provisional application No. 61/407,377, filed 10/27/2010. Application No. 13/967,665 also claims priority to provisional Application No. 61/684,221, filed 08/17/2012. The earliest filed application that provides sufficient support for the limitations of a signal correction parameter determined based on signal data of a plurality of other sample-containing wells of the instant application is provisional Application No. 61/684,221, filed 08/17/2012.
Therefore, the Effective Filing Date (EFD) assigned to each of the claims 1-13 is the provisional filing date of Application No. 61/684,221, filed 08/17/2012.
Information Disclosure Statement
No Information Disclosure Statement has been filed herein.
Drawings
The drawings filed 09/06/2022 are objected to because Figs. 2-3B include enumerated nucleic acid sequences without a sequence identifier (see below).
Nucleotide and/or Amino Acid Sequence Disclosures
The Sequence Listing filed 11/23/2022 is accepted.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
In paragraph [0063], “3-mer, etc can also” should read “3-mer, etc. can also”
In paragraph [0072], “the final signal correction parameter(s) can then used” should read “the final signal correction parameter(s) can then be used”
On page 26, paragraph [0079], “the subsets of wells selected for parameter estimation may to used to” should read “the subsets of wells selected for parameter estimation may be used to”
In paragraph [0099], “fluidics controller 118, which may programmed” should read “fluidics controller 118, which may be programmed”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-13 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.
With respect to claim 1, the claim recites “a machine-readable memory” and in step (c), “wherein the model is stored in a machine-readable memory”. The claim is indefinite because it is unclear if the memory that the model is stored in is the machine-readable medium of the system, or a different machine-readable memory.
With further respect to claim 1, in step (g), the claim recites the limitation of “storing the fitted signal correction parameter in the memory”. Due to the indefiniteness described above, where there are two recite memories, it is unclear which memory the fitted signal correction parameter is stored in.
The remaining claims are rejected due to be dependent upon indefinite claims without remedying the indefiniteness.
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 1-13 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims recite a system.
With respect to step (2A)(1): The claims are directed to abstract ideas of mental processes and mathematical concepts.
“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). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claim 1:
determining sequence information for the sample nucleic acid template using signal data from the first well containing the ample nucleic acid template
comparing the predicted signals to the signal data from the plurality of other sample-containing wells
Mathematical concepts recited in claim 1:
constructing a phase-state model for a set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter that is determined using signal data from the plurality of other sample-containing wells
calculating, using the phase-state model, predicted signals for the plurality of other sample-containing wells resulting from the set of nucleotide flows
fitting the signal correction parameter of the phase-state model based on the comparison of the predicted signals to the signal data from the plurality of other sample-containing wells
Dependent claims 2-13 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claim 1, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 2: “wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and without using signal data obtain from the first well”
Claim 3: “wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and signal obtain from the first well”
Claim 4: “performing steps (b) through (g) for each of the obtained signal data from each of the plurality of other sample-containing wells to obtain multiple fitted signal correction parameters, wherein each of the multiple fitted signal correction parameters is determined for a given well without using signal data from that given well”
Claim 5: “wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data”
Claim 6: “wherein the phase-state model includes two or more signal correction parameters, including a carry forward rate and an incomplete extension rate”
Claim 7: “wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data”
Claim 8: “wherein the fitting step comprises determining a value of the signal correction parameter that optimizes the fitting metric”
Claim 9: “wherein the fitting step comprises determining a value of the signal correction parameter using a Nelder-Mead optimization”
Claim 10: “wherein the fitting metric is calculated using only nucleotide flows that result in nucleotide non-incorporations or single nucleotide incorporations”
Claim 11: “performing a base calling analysis of the signal data using the fitted signal correction parameter”
Claim 12: “wherein the set of nucleotide flows is a first set of nucleotide flows and the sequence information is a first sequence information, the steps further comprising: applying the phase-state model using the fitted signal correction parameter, calculating, using the phase-state model and the fitted signal correction parameter obtained using signal data from the plurality of other sample-containing wells, predicted signals for the first well resulting from a second set of nucleotide flows that includes nucleotide flows that are not in the first set of nucleotide flows, making base calls by comparing the signal data from the first well to the predicted signals for the first well, and obtaining a second sequence information about the sample nucleic acid template, wherein the second sequence information includes sequence information not contained in the first sequence information”
Claim 13: “repeating steps (d) through (g) using the second sequence information to obtain a further fitted signal correction parameter”
The abstract ideas in the claims are evaluated under Broadest Reasonable Interpretation (BRI) and determined herein to each cover mental processes and mathematic concepts because the claims recite no more than analyzing sequence data and performing mathematical concepts to construct a model and using this model to calculate further values to make a prediction.
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claim 1 recites the following additional elements that are not abstract ideas:
system comprising a machine-readable memory and a processor configured to execute machine-readable instruction which are configured to, when executed by the processor, cause the system to perform the steps
measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto a sensor array comprising a plurality of region of wells, at least one of the wells comprising: (i) a first set of wells including a first well containing the sample nucleic acid template and (ii) a second set of wells including a plurality of other sample-containing wells
wherein the model is stored in a machine-readable memory
storing the fitted signal correction parameter in the memory
The step of measuring signal data relating to nucleotide incorporation events gathers the data on which the judicial exceptions are performed and is thus directed to data gathering. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)). The steps of storing the fitted signal correction parameter and storing the model in memory is ancillary to the judicial exception and does not integrate the judicial exceptions into a practical application. The system comprising a machine-readable memory and processor is directed to a generic computer. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc. ... are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (see MPEP 2106.05(f)).
None of the dependent claims recite additional elements, alone or in combination, which would integrate a judicial exception into a practical application.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP 2106.05(d).I, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claim 1: The additional elements of system comprising a machine-readable memory and a processor configured to execute machine-readable instruction which are configured to, when executed by the processor, cause the system to perform the steps, measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto a sensor array comprising a plurality of region of wells, at least one of the wells comprising: (i) a first set of wells including a first well containing the sample nucleic acid template and (ii) a second set of wells including a plurality of other sample-containing wells, the model being stored in a machine-readable memory, and storing the fitted signal correction parameter in the memory do not rise to the level of significantly more than the judicial exception. With respect to the computing system, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “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”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). With respect to storing the model and the fitted signal correction parameter in a memory, as exemplified in the MPEP at 2106.05(d).II with respect to Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, storing and retrieving information in memory is a well-understood, routine, and conventional technique. With respect to measuring signal data relating to nucleotide incorporation events, in paragraph [0003], the Specification of the instant claims discloses numerous techniques for sequencing-by-synthesis. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10273540. Although the claims at issue are not identical, they are not patentably distinct from each other because Patent ‘540 discloses a computing system performing the embodiments of the invention.
Instant Claims
Patent ‘540
Claim(s)
Limitation
Claim(s)
Limitation
1
A system for estimating a parameter related to sequencing of a sample nucleic acid template, comprising: a machine-readable memory; and a processor configured to execute machine-readable instructions, which are configured to, when executed by the processor, cause the system to perform steps, comprising:(a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto a sensor array comprising a plurality of regions of wells, at least one of the regions of wells comprising: (i) a first set of wells including a first well containing the sample nucleic acid template and (ii) a second set of wells including a plurality of other sample-containing wells,(b) determining sequence information for the sample nucleic acid template using signal data from the first well containing the sample nucleic acid template;(c) constructing a phase-state model for a set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter that is determined using signal data from the plurality of other sample-containing wells, and wherein the model is stored in a machine-readable memory;(d) calculating, using the phase-state model, predicted signals for the plurality of other sample-containing wells resulting from the set of nucleotide flows;(e) comparing the predicted signals to the signal data from the plurality of other sample- containing wells;(f) fitting the signal correction parameter of the phase-state model based on the comparison of the predicted signals to the signal data from the plurality of other sample-containing wells; and(g) storing the fitted signal correction parameter in the memory.
1
A method of estimating a parameter related to sequencing of a sample nucleic acid template, comprising: (a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto a sensor array comprising a plurality of regions of wells, at least one of the regions of wells comprising: (i) a first set of wells including a first well containing the sample nucleic acid template and (ii) a second set of wells including a plurality of other sample-containing wells, wherein the first set of wells and the second set of wells are physically distinguishable from each other by shape or dimension; (b) determining sequence information for the sample nucleic acid template using signal data from the first well containing the sample nucleic acid template; (c) constructing a phase-state model for a set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter that is determined using signal data from the plurality of other sample-containing wells, and wherein the model is stored in a machine-readable memory; (d) calculating, using the phase-state model, predicted signals for the plurality of other sample-containing wells resulting from the set of nucleotide flows; (e) comparing the predicted signals to the signal data from the plurality of other sample-containing wells; (f) fitting the signal correction parameter of the phase-state model based on the comparison of the predicted signals to the signal data from the plurality of other sample-containing wells; and (g) storing the fitted signal correction parameter in the memory.
2
wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and without using signal data obtained from the first well
2
wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and without using signal data obtained from the first well
3
wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and signal data obtained from the first well
3
wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and signal data obtained from the first well
4
further comprising: performing steps (b) through (g) for each of the obtained signal data from each or some of the plurality of other sample-containing wells to obtain multiple fitted signal correction parameters, wherein each of the multiple fitted signal correction parameters is determined for a given well without using signal data from that given well
4
further comprising: performing steps (b) through (g) for each of the obtained signal data from each or some of the plurality of other sample-containing wells to obtain multiple fitted signal correction parameters, wherein each of the multiple fitted signal correction parameters is determined for a given well without using signal data from that given well
5
wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
5
wherein the comparing step comprises calculating a fitting metric that measures the fit between the predicted signals and the signal data
6
wherein the phase-state model includes two or more signal correction parameters, including a carry forward rate and an incomplete extension rate
6
wherein the phase-state model includes two or more signal correction parameters, including a carry forward rate and an incomplete extension rate
7
wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
7
wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
8
wherein the fitting step comprises determining a value of the signal correction parameter that optimizes the fitting metric
8
wherein the fitting step comprises determining a value of the signal correction parameter that optimizes the fitting metric
9
wherein the fitting step comprises determining a value of the signal correction parameter using a Nelder-Mead optimization
9
wherein the fitting step comprises determining a value of the signal correction parameter using Nelder-Mead optimization
10
wherein the fitting metric is calculated using only nucleotide flows that result in nucleotide non-incorporations or single nucleotide incorporations
10
wherein the fitting metric is calculated using only nucleotide flows that result in nucleotide non-incorporation or single nucleotide incorporations
11
further comprising performing a base calling analysis of the signal data using the fitted signal correction parameter
11
further comprising performing a base calling analysis of the signal data using the fitted signal correction parameter
12
wherein the set of nucleotide flows is a first set of nucleotide flows and the sequence information is a first sequence information, the steps further comprising: applying the phase-state model using the fitted signal correction parameter, calculating, using the phase-state model and the fitted signal correction parameter obtained using signal data from the plurality of other sample-containing wells, predicted signals for the first well resulting from a second set of nucleotide flows that includes nucleotide flows that are not in the first set of nucleotide flows, making base calls by comparing the signal data from the first well to the predicted signals for the first well, and obtaining a second sequence information about the sample nucleic acid template, wherein the second sequence information includes sequence information not contained in the first sequence information
12
wherein the set of nucleotide flows is a first set of nucleotide flows and the sequence information is a first sequence information, and further comprising: applying the phase-state model using the fitted signal correction parameter; calculating, using the phase-state model and the fitted signal correction parameter obtained using signal data from the plurality of other sample-containing wells, predicted signals for the first well resulting from a second set of nucleotide flows that includes nucleotide flows that are not in the first set of nucleotide flows; making base calls by comparing the signal data from the first well to the predicted signals for the first well; and obtaining a second sequence information about the sample nucleic acid template, wherein the second sequence information includes sequence information not contained in the first sequence information
13
further comprising repeating steps (d) through (g) using the second sequence information to obtain a further fitted signal correction parameter
13
further comprising repeating steps (d) through (g) using the second sequence information to obtain a further fitted signal correction parameter
Although the claims of patent ‘540 are silent with regard to a system comprising a machine-readable memory and processor, the patent discloses in column 27, line 17 that the embodiments may be implemented using a computing system comprising a processor and a machine-readable medium comprising instructions with executable code. Thus, it would be obvious to one of ordinary skill to implement the method of claim 1 of patent ‘540 using a computing system comprising a processor and computer-readable medium.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11453912. Although the claims at issue are not identical, they are not patentably distinct from each other on view of the disclosure of the Patent.
Instant Claims
Patent ‘912
Claim(s)
Limitation
Claim(s)
Limitation
1
A system for estimating a parameter related to sequencing of a sample nucleic acid template, comprising: a machine-readable memory; and a processor configured to execute machine-readable instructions, which are configured to, when executed by the processor, cause the system to perform steps, comprising:(a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto a sensor array comprising a plurality of regions of wells, at least one of the regions of wells comprising: (i) a first set of wells including a first well containing the sample nucleic acid template and (ii) a second set of wells including a plurality of other sample-containing wells,(b) determining sequence information for the sample nucleic acid template using signal data from the first well containing the sample nucleic acid template;(c) constructing a phase-state model for a set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter that is determined using signal data from the plurality of other sample-containing wells, and wherein the model is stored in a machine-readable memory;(d) calculating, using the phase-state model, predicted signals for the plurality of other sample-containing wells resulting from the set of nucleotide flows;(e) comparing the predicted signals to the signal data from the plurality of other sample- containing wells;(f) fitting the signal correction parameter of the phase-state model based on the comparison of the predicted signals to the signal data from the plurality of other sample-containing wells; and(g) storing the fitted signal correction parameter in the memory.
1
A method of sequencing a sample nucleic acid template, comprising: (a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto an array of wells including (i) a first well containing the sample nucleic acid template and (ii) a plurality of other sample-containing wells, wherein the array includes a sensor array for detecting the signal data related to the chemical reactions resulting from the flow of nucleotides, wherein the signal data are received from the sensor array; (b) determining preliminary sequence information for the sample nucleic acid template using the signal data from the first well; (c) constructing a phase-state model for a first set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter fitted by comparing signal data from the plurality of other sample-containing wells to predicted signals for the plurality of other sample-containing wells resulting from the first set of nucleotide flows, and wherein the model is stored in a machine-readable memory; and (d) determining revised sequence information for the sample nucleic acid template by performing a base calling analysis of the signal data from the first well using the signal correction parameter fitted based on signal data from the plurality of other sample-containing wells, wherein the first well containing the sample nucleic acid template is part of a first set of wells in a first region of the array, the plurality of other sample-containing wells are part of a second set of wells in the first region of the array, and the first set of wells and the second set of wells are distinguishable from one another within the first region of the array by shape, dimension, or inclusion in a defined spatial arrangement that is an alternating arrangement wherein positions of the wells of the first set of wells alternate with positions of the wells of the second set of wells, and wherein the array further includes additional regions of the array that have additional respective first and second sets of wells that are distinguishable from one another within each of the additional regions of the array
2
wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and without using signal data obtained from the first well
3
further comprising: performing steps (c) and (d) for the signal data from each or some of the plurality of other sample-containing wells to obtain multiple signal correction parameters, wherein each of the multiple signal correction parameters is determined for a given well without using signal data from that given well
3
wherein the signal correction parameter is obtained using signal data obtained from at least a portion of the plurality of other sample-containing wells and signal data obtained from the first well
1
A method of sequencing a sample nucleic acid template, comprising: (a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto an array of wells including (i) a first well containing the sample nucleic acid template and (ii) a plurality of other sample-containing wells, wherein the array includes a sensor array for detecting the signal data related to the chemical reactions resulting from the flow of nucleotides, wherein the signal data are received from the sensor array; (b) determining preliminary sequence information for the sample nucleic acid template using the signal data from the first well; (c) constructing a phase-state model for a first set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter fitted by comparing signal data from the plurality of other sample-containing wells to predicted signals for the plurality of other sample-containing wells resulting from the first set of nucleotide flows, and wherein the model is stored in a machine-readable memory; and (d) determining revised sequence information for the sample nucleic acid template by performing a base calling analysis of the signal data from the first well using the signal correction parameter fitted based on signal data from the plurality of other sample-containing wells, wherein the first well containing the sample nucleic acid template is part of a first set of wells in a first region of the array, the plurality of other sample-containing wells are part of a second set of wells in the first region of the array, and the first set of wells and the second set of wells are distinguishable from one another within the first region of the array by shape, dimension, or inclusion in a defined spatial arrangement that is an alternating arrangement wherein positions of the wells of the first set of wells alternate with positions of the wells of the second set of wells, and wherein the array further includes additional regions of the array that have additional respective first and second sets of wells that are distinguishable from one another within each of the additional regions of the array
4
further comprising: performing steps (b) through (g) for each of the obtained signal data from each or some of the plurality of other sample-containing wells to obtain multiple fitted signal correction parameters, wherein each of the multiple fitted signal correction parameters is determined for a given well without using signal data from that given well
3
further comprising: performing steps (c) and (d) for the signal data from each or some of the plurality of other sample-containing wells to obtain multiple signal correction parameters, wherein each of the multiple signal correction parameters is determined for a given well without using signal data from that given well
5
wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
6
wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
6
wherein the phase-state model includes two or more signal correction parameters, including a carry forward rate and an incomplete extension rate
4
wherein the phase-state model includes two or more signal correction parameters, including a carry forward rate and an incomplete extension rate
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wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
6
wherein the comparing step comprises calculating a fitting metric that measures a fit between the predicted signals and the signal data
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wherein the fitting step comprises determining a value of the signal correction parameter that optimizes the fitting metric
7
wherein the fitting step comprises determining a value of the signal correction parameter that optimizes the fitting metric
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further comprising performing a base calling analysis of the signal data using the fitted signal correction parameter
1
A method of sequencing a sample nucleic acid template, comprising: (a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto an array of wells including (i) a first well containing the sample nucleic acid template and (ii) a plurality of other sample-containing wells, wherein the array includes a sensor array for detecting the signal data related to the chemical reactions resulting from the flow of nucleotides, wherein the signal data are received from the sensor array; (b) determining preliminary sequence information for the sample nucleic acid template using the signal data from the first well; (c) constructing a phase-state model for a first set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter fitted by comparing signal data from the plurality of other sample-containing wells to predicted signals for the plurality of other sample-containing wells resulting from the first set of nucleotide flows, and wherein the model is stored in a machine-readable memory; and (d) determining revised sequence information for the sample nucleic acid template by performing a base calling analysis of the signal data from the first well using the signal correction parameter fitted based on signal data from the plurality of other sample-containing wells, wherein the first well containing the sample nucleic acid template is part of a first set of wells in a first region of the array, the plurality of other sample-containing wells are part of a second set of wells in the first region of the array, and the first set of wells and the second set of wells are distinguishable from one another within the first region of the array by shape, dimension, or inclusion in a defined spatial arrangement that is an alternating arrangement wherein positions of the wells of the first set of wells alternate with positions of the wells of the second set of wells, and wherein the array further includes additional regions of the array that have additional respective first and second sets of wells that are distinguishable from one another within each of the additional regions of the array
12
wherein the set of nucleotide flows is a first set of nucleotide flows and the sequence information is a first sequence information, the steps further comprising: applying the phase-state model using the fitted signal correction parameter, calculating, using the phase-state model and the fitted signal correction parameter obtained using signal data from the plurality of other sample-containing wells, predicted signals for the first well resulting from a second set of nucleotide flows that includes nucleotide flows that are not in the first set of nucleotide flows, making base calls by comparing the signal data from the first well to the predicted signals for the first well, and obtaining a second sequence information about the sample nucleic acid template, wherein the second sequence information includes sequence information not contained in the first sequence information
1
A method of sequencing a sample nucleic acid template, comprising: (a) measuring signal data relating to nucleotide incorporation events resulting from a series of flows of nucleotides onto an array of wells including (i) a first well containing the sample nucleic acid template and (ii) a plurality of other sample-containing wells, wherein the array includes a sensor array for detecting the signal data related to the chemical reactions resulting from the flow of nucleotides, wherein the signal data are received from the sensor array; (b) determining preliminary sequence information for the sample nucleic acid template using the signal data from the first well; (c) constructing a phase-state model for a first set of nucleotide flows that contributed at least in part to the sequence information, wherein the model includes a signal correction parameter fitted by comparing signal data from the plurality of other sample-containing wells to predicted signals for the plurality of other sample-containing wells resulting from the first set of nucleotide flows, and wherein the model is stored in a machine-readable memory; and (d) determining revised sequence information for the sample nucleic acid template by performing a base calling analysis of the signal data from the first well using the signal correction parameter fitted based on signal data from the plurality of other sample-containing wells, wherein the first well containing the sample nucleic acid template is part of a first set of wells in a first region of the array, the plurality of other sample-containing wells are part of a second set of wells in the first region of the array, and the first set of wells and the second set of wells are distinguishable from one another within the first region of the array by shape, dimension, or inclusion in a defined spatial arrangement that is an alternating arrangement wherein positions of the wells of the first set of wells alternate with positions of the wells of the second set of wells, and wherein the array further includes additional regions of the array that have additional respective first and second sets of wells that are distinguishable from one another within each of the additional regions of the array
13
further comprising repeating steps (d) through (g) using the second sequence information to obtain a further fitted signal correction parameter
3
further comprising: performing steps (c) and (d) for the signal data from each or some of the plurality of other sample-containing wells to obtain multiple signal correction parameters, wherein each of the multiple signal correction parameters is determined for a given well without using signal data from that given well
Although the claims of Patent ‘912 are silent with regard to a computing system comprising a machine-readable memory and processor, the patent discloses in column 27, line 6 that the embodiments may be implemented using a computing system comprising a processor and a machine-readable medium comprising instructions with executable code. Thus, it would be obvious to one of ordinary skill to implement the method of claim 1 of patent ‘540 using a computing system comprising a processor and computer-readable medium.
Furthermore, although the claims of Patent ‘912 are silent with regard to storing the fitted signal correction parameter in the memory, the patent discloses in column 2, line 44, “storing the fitted signal correction parameter in the memory”. Thus, it would be obvious to one of ordinary skill to perform the method and choose to store the fitted signal correction parameter in the memory based on the disclosure.
Furthermore, although the claims of Patent ‘912 are silent with regard to determining a value of the signal correction parameter using a Nelder-Mead optimization and the fitting metric being calculated using only nucleotide flows that result in nucleotide non-incorporations or single nucleotide incorporations, the patent discloses in column 20, line 52 that the fitting metric may be calculated using only nucleotide flows that result in nucleotide non-incorporation or single nucleotide incorporations, and that the fitting step may comprise determining a value of the signal correction parameter using Nelder-Mead optimization.
Conclusion
No claims are allowed.
The claims appear to be free from the art because while the closest prior art to Kao et al. (“BayesCall: A model-based base-calling algorithm for high-throughput short-read sequencing”, Genome Research, published August 2009) does teach programs to analyze the accuracy of base calling from data of a sensor array, a cycle-dependent parameter model, and cycle-dependent parameters, Kao et al. does not appear to teach or fairly suggest calculating, using the phase-state mode, predicted signals, and fitting a signal correction parameter of the phase-state model based on the comparison of predicted signals and actual signal data.
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/E.A.S./Examiner, Art Unit 1686
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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