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 1-31 are pending and examined herein.
Claims 1-31 are rejected.
Priority
Claims 1-31 are granted the claim to the benefit of priority to U.S. Provisional application 63/223408 filed 19 July 2021. Thus, the effective filling date of claims 1-31 is 19 July 2021.
Information Disclosure Statement
The information disclosure statements (IDS) were received on 16 November 2022, 05 January 2023, 12 October 2023, 30 May 2024, 19 December 2024, 01 May 2025, 17 July 2025, 18 September 2025, and 18 December 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Drawings
The drawings received 13 June 2022 are objected to for the reasons stated below.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character “100” has been used to designate both a “sequencing environment with an imaging system” and a “fluid delivery module or device” (in figure 1) and reference character “210” has been used to designate different structures in figure 1 and figure 2 (it appears 210 in figure 1 should be 110). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: “110”, “185”, and “2354”. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: “141” (in figure 1), “504” (in figure 5A), “1418” (in figure 14), “1852” (in figure 18), “2112” (in figure 21), “2122” (in figure 21), “2126” (in figure 21), “2364” (in figure 23), “2602” (in figure 26), “2702” (in figure 27), “2802” (in figure 28), and “2902” (in figure 29). Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The drawings are objected to because they fail to comply with 37 CFR 1.84(u)(1) which states view numbers must be preceded by the abbreviation "FIG." (see MPEP 608.02(V) section 37 CFR 1.84(u)(1)). Therefore, ““Figure 1”, “Figure 2”, …” should read ““FIG. 1”, “FIG. 2”, …”. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The specification is objected to because the abstract reads “We disclose a system” which is a phrase that can be implied.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Interpretation
Claims 1, 18, 22, 23, 24, 29, and 31 recite “specialist signal profiler” and “specialist signal profilers”. The instant disclosure provides a “specialist signal profiler” is a signal profiler that is configured to/trained to maximize the signal-to-noise ratio of a particular category/type/ configuration/characteristic/class/bin of data (instant disclosure [0088]). The instant disclosure provides that a “signal profiler” maximizes the signal-to-noise ratio of a signal that is distributed by noise and that the signal profiler can be a mathematical formula, logic function, computer implemented algorithm, or the like (instant disclosure [0073]). The instant disclosure further provides that the signal profiler can be applied to the data by any variety of mathematical manipulations such as addition, subtraction, division, multiplication, or a combination thereof (instant disclosure [0073]).
112/f Claim interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitations are: “runtime logic, having access to the memory, configured to execute a base calling operation by…” in claims 1, “the runtime logic is further configured to execute the base calling operation by…” in claim 18, “the runtime logic is further configured to iteratively train the…” in claim 23, “the runtime logic is further configured to implement expectation maximization that…” in claim 24, “fitting logic, having access to the memory, configured to fit a plurality of signal distributions…” in claim 29, “online training logic, having access to the memory, configured to train respective specialist signal profilers…” in claim 29, “runtime logic, having access to the memory, configured to uniquely map…” in claim 29, “fitting logic, having access to the memory, configured to process the…” in claim 31, “online training logic, having access to the memory, configured to train respective specialist signal profilers” in claim 31, and “runtime logic, having access to the memory, configured to uniquely map…” in claim 31.
In review of the instant disclosure, there is not a clear link to a structure for “runtime logic” that performs the functions recited, “fitting logic” that performs the functions recited, or “online training logic” that performs the functions recited. See 112/a and 112/b rejections below.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
112/a
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 18, 23, 24, 29, and 31 recite “runtime logic… configured to” and claims 29 and 31 further recite “fitting logic… configured to” and “online training logic… configured to”. The MPEP states that when a claim containing a computer-implemented 35 U.S.C. 112(f) claim limitation is found to be indefinite under 35 U.S.C. 112(b) for failure to disclose sufficient corresponding structure (e.g., the computer and the algorithm) in the specification that performs the entire claimed function, it will also lack written description under 35 U.S.C. 112(a). See MPEP § 2163.03, subsection VI (MPEP 2181(IV)). There is not an adequate written description of a corresponding structure (the computer and the algorithm) in the specification that performs the entire claimed function for “runtime logic… configured to”, “fitting logic… configured to”, and “online training logic… configured to”. Dependent claims 2-17, 19-21, 25-28, and 30 are rejected by virtue of their dependency on rejected claims without alleviating the rejection.
112/b
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-31 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.
Claims 10 and 11 recite “the different swath groups” in line 1 of the claims. There is insufficient antecedent basis for this limitation in the claims. The indefiniteness arises because the claim does not make clear what “the different swath groups” is referring to. This rejection could be overcome by amendment of this limitation to “the different swathes”. For the sake of furthering examination, this limitation will be interpreted as the different swathes.
Claim 24 recites “wherein, for a current training iteration, the runtime logic is further configured to implement expectation maximization that iteratively maximizes a likelihood of channel-wise observing base-wise signal centroids and signal distributions that best fit sequenced signals detected so far during the base calling operation, to channel-wise determine signal-to- noise ratio-maximized sequenced signals…, to call bases based on the signal-to-noise ratio-maximized sequenced signals, to channel-wise determine base calling errors…, and to channel-wise update coefficients of convolution kernels…” which renders the metes and bounds of the claim indefinite. The indefiniteness arises because it is unclear if the limitations “to channel-wise determine…”, “to call bases…”, “to channel-wise determine base calling errors”, and “to channel-wise update coefficients of convolution kernels…” are part of a list of what the runtime logic is further configured to implement. The specification does not provide a clear and precise definition of the limitation, nor would one skilled in the art recognize the metes and bounds of said limitation. For the sake of furthering examination, this limitation will be interpreted as for each iteration fitting training data by optimizing parameters. If these functions are part of a list of what the runtime logic is further configured to implement this rejection may be overcome by clarifying grammar and/or formatting to make clear these are functions the runtime logic is configured to perform such as “the runtime logic is further configured to implement: “expectation maximization…”, “determine channel-wise signal-to-noise…”, “call bases based on the signal-to-noise…”, “determine channel-wise base calling errors…”, and “update channel-wise coefficients of convolution kernels…”.
Claim limitations “runtime logic, having access to the memory, configured to execute a base calling operation by…” in claims 1, “the runtime logic is further configured to execute the base calling operation by…” in claim 18, “the runtime logic is further configured to iteratively train the…” in claim 23, “the runtime logic is further configured to implement expectation maximization that…” in claim 24, “fitting logic, having access to the memory, configured to fit a plurality of signal distributions…” in claim 29, “online training logic, having access to the memory, configured to train respective specialist signal profilers…” in claim 29, “runtime logic, having access to the memory, configured to uniquely map…” in claim 29, “fitting logic, having access to the memory, configured to process the…” in claim 31, “online training logic, having access to the memory, configured to train respective specialist signal profilers” in claim 31, and “runtime logic, having access to the memory, configured to uniquely map…” in claim 31 invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function.
Claim 1 recites “runtime logic, having access to the memory, configured to execute a base calling operation by…”, claim 18 recites “the runtime logic is further configured to execute the base calling operation by…”, claim 23 recites “the runtime logic is further configured to iteratively train the…”, and claim 24 recites “the runtime logic is further configured to implement expectation maximization that…” which renders the metes and bounds of the claim indefinite. The written description fails to disclose corresponding structure for performing these functions because there is no clear link between a structure (such as a processor). Further, the written description does not provide that the runtime logic is configured to iteratively train specialist signal profilers (it only provides that the runtime logic applies trained specialist signal profilers [00162] while training logic trains these profilers). Dependent claims 2-17, 19-22, and 24-28 are rejected by virtue of their dependency on a rejected claim without alleviating the indefiniteness. For the sake of furthering examination “runtime logic” will be interpreted as a processor.
Claim 29 recites “fitting logic, having access to the memory, configured to fit a plurality of signal distributions…”, “online training logic, having access to the memory, configured to train respective specialist signal profilers…”, and “runtime logic, having access to the memory, configured to uniquely map…” which renders the metes and bounds of the claim indefinite. The written description fails to disclose corresponding structure of fitting logic, online training logic, and runtime logic for performing these functions because there is no clear link between a structure (such as a processor). Further, there is no disclosure of “fitting logic” in the written description and there is no disclosure of “runtime logic” which uniquely maps sequenced signals to distributions. Dependent claim 30 is rejected by virtue of their dependency on a rejected claim without alleviating the indefiniteness. For the sake of furthering examination “fitting logic”, “online training logic”, and “runtime logic” will be interpreted as a processor.
Claim 31 recites “fitting logic, having access to the memory, configured to process the…”, “online training logic, having access to the memory, configured to train respective specialist signal profilers”, and “runtime logic, having access to the memory, configured to uniquely map…” which renders the metes and bounds of the claim indefinite. The written description fails to disclose corresponding structure of fitting logic, online training logic, and runtime logic for performing these functions because there is no clear link between a structure (such as a processor). Further, there is no disclosure of “fitting logic” in the written description and there is no disclosure of “runtime logic” which uniquely maps sequenced signals to distributions. For the sake of furthering examination “fitting logic”, “online training logic”, and “runtime logic” will be interpreted as a processor.
Therefore, the claims 1-31 are indefinite and are rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
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 1-31 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.
(Step 1)
Claims 1-31 are directed to a machine.
(Step 2A Prong 1)
Under the BRI, the instant claims recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mental process”, such as procedures for evaluating, analyzing or organizing information, and forming judgement or an opinion. The instant claims further recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mathematical concept”, such as mathematical relationships and mathematical equations.
Independent claim 1 recites a mental process and mathematical concept of “execute a base calling operation by applying respective specialist signal profilers…”.
Independent claim 29 recites mathematical concepts of “fit a plurality of signal distributions on the initially sequenced signals”, “train respective specialist signal profilers in a plurality of specialist signal profilers…”, and “uniquely map subsequently sequenced signals detected during subsequent sequencing cycles of the sequence run to the respective signal distributions, and to apply the trained respective specialist signal profilers…”.
Independent claim 31 recites mathematical concepts of “process the initially sequenced signals on an analyte-by-analyte basis, to fit respective signal profiles…”, “train respective specialist signal profilers in a plurality of specialist signal profilers…”, and “uniquely map subsequently sequenced signals detected during subsequent sequencing cycles of the sequence run to the respective signal profilers on the analyte-by-analyte basis, and to apply the trained respective specialist signal profilers…”.
Claim 18 recites a mathematical concept of “execute the base calling operation by applying the respective specialist signal profilers to…”. Claim 23 recites a mathematical concept of “iteratively train the respective specialist signal profilers during the base calling operation”. Claim 21 recites a mathematical concept of “iteratively train the respective specialist signal profilers during the base calling operation”. Claim 22 recite a mathematical concept of for each iteration fitting training data by optimizing parameters.
The claims recite mathematical concepts that fall under mathematical calculations as “execute a base calling operation by applying respective specialist signal profilers” (the instant disclosure provides applying signal profilers encompasses mathematical operations [0073] and [0088]), fitting intensity data (the instant disclosure provides this is done by fitting mathematical models [0119]), training signal profilers (the instant disclosure provides using least square estimation which is a series of mathematical calculations [0074]), and mapping signals (the instant disclosure provides this can be done by generating a likelihood using an EM algorithm which is a series of mathematical calculations [0119]). Dependent claims 2-20, 25-28, and 30 further limit the mathematical concept recited in the independent claim but do not change their nature as a mental process/mathematical concept.
(Step 2A Prong 2)
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). Integration into a practical application is evaluated by identifying whether there are any additional elements recited in the claim and evaluating those additional elements to determine whether they integrate the exception into a practical application.
The additional element in claims 1, 29, and 31 of a system comprising a memory and logic (which is interpreted as a processor) does not integrate the judicial exceptions into a practical application because this is using a generic computer to perform judicial exceptions without an improvement to computer technology. This additional element of a generic computer only interacts with the judicial exceptions by being utilized as a tool to perform judicial exceptions.
Thus, the additional elements do not integrate the judicial exceptions into a practical application and claims 1-31 are directed to the abstract idea.
(Step 2B)
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because:
The additional element in claims 1, 29, and 31 of a system comprising a memory and logic (which is interpreted as a processor) is conventional as shown by MPEP 2106.05(b) and MPEP 2106.05(d)(II).
Thus, the additional elements are not sufficient to amount to significantly more than the judicial exception because they are conventional.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 29 and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Belitz et al. (US 20180274023 A1; cited in IDS received 05 January 2023).
Claim 29 is directed to a system, comprising: memory storing initially sequenced signals detected during initial sequencing cycles of a sequencing run; fitting logic, having access to the memory, configured to fit a plurality of signal distributions on the initially sequenced signals, and to store the plurality of signal distributions in the memory;
Belitz et al. shows fitting four Gaussian distributions to a set of two-channel intensity data such that one distribution is applied for each of the four nucleotides represented in the data set (Belitz et al. [0153]).
online training logic, having access to the memory, configured to train respective specialist signal profilers in a plurality of specialist signal profilers to maximize signal-to-noise ratio of respective signal distributions in the plurality of signal distributions, and to store the trained respective specialist signal profilers in the memory;
Belitz et al. shows calculating a separate phasing correction for every tile at every cycle where the phasing correction for a given cycle is a mathematical formula for correcting intensity at a given cycle (Belitz et al. [0098]-[0100]). Belitz et el. shows numerically optimizing via a pattern search over phasing coefficients to maximize the mean chastity and once the phasing coefficient values are identified with maximal mean chastity, the phasing correction can be applied and then base calling can occur directly subsequent (Belitz et al. [0098]). Phasing correction for a particular tile and cycle is interpreted as a specialist signal profiler because it maximizes signal-to-noise ratio of signal distributions.
and runtime logic, having access to the memory, configured to uniquely map subsequently sequenced signals detected during subsequent sequencing cycles of the sequence run to the respective signal distributions, and to apply the trained respective specialist signal profilers to the subsequently sequenced signals based on the unique mapping to the respective signal distributions to generate base calls for the subsequent sequencing cycles.
Belitz et al. shows an EM algorithm that for X and Y intensity values (referring to each of the two channel intensities respectively) a value can be generated which represents the likelihood that certain X, Y intensity value belongs to one of the four distributions which is interpreted as mapping signals to respective signal distributions (Belitz et al. [0154]). Belitz et al. shows applying phasing correction (specialist signal profiler) then performing base calling (Belitz et al. [0098]).
Claim 30 is directed to wherein at least some of the signal distributions in the plurality of signal distributions are representative of different underlying sequencing events that contribute to creation of the some of the signal distributions.
Belitz et al. shows four Gaussian distributions for a set of two-channel intensity data such that one distribution is applied for each of the four nucleotides represented in the data set (Belitz et al. [0153]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-28 are rejected under 35 U.S.C. 103 as being unpatentable over Kostem (US 20200364565 A1; cited in IDS received 16 November 2022) in view of Langlois et al. (US 20180195953 A1; cited in IDS received 05 January 2023).
Claim 1 is directed to a system comprising: memory storing a plurality of specialist signal profilers, wherein each specialist signal profiler in the plurality of specialist signal profilers is trained to maximize signal-to-noise ratio of sequenced signals in a particular signal profile detected for analytes in a particular analyte class and characterized in a particular training data set and
Kostem shows 3D convolution filters (each filter is interpreted as being a specialist signal profiler which convolves over a corresponding per-cycle image patch) are trained on image data by an optimization process which includes adjusting/evolving/updating the coefficients/ weights/parameters of the convolution kernels (and biases) of the 3D convolution filters to minimize the loss between the predicted base calls and the correct base calls identified by the ground truth (Kostem [0152] and [0157]). Kostem shows a per-cycle image whose pixels depict pixel signals for a subset of the pixel areas (i.e. a region (tile)) of the detection surface of the biosensor is called a “per-cycle tile image” and a patch extracted from a per-cycle tile image is called a “per-cycle image patch” (Kostem [0131]).
runtime logic, having access to the memory, configured to execute a base calling operation by applying respective specialist signal profilers in the plurality of specialist signal profilers to sequenced signals in respective signal profiles detected for analytes in respective analyte classes during the base calling operation.
Kostem shows 3D convolutions detect and account for biases during a convolution-based base calling by utilizing 3D convolution filters of the 3D convolutions (which is interpreted as being a signal profiler) (Kostem et al. [0152]). Kostem shows a 3D convolution filter convolve over - a plurality of the per-cycle image patches along a temporal dimension to detect and account for phasing and pre-phasing effect between successive ones of the sequencing cycles caused by asynchronous readout of sequence copies of an associated analyte, a plurality of pixels in each of the per-cycle image patches along spatial dimensions to detect and account for spatial crosstalk between adjacent analytes caused by detection of emissions from a non-associated analyte by a corresponding light sensor of an associated analyte and each of the imaged channels along a depth dimension to detect and account for emission overlap between the imaged channels caused by overlap of dye emission spectra (Kostem [0152]). Kostem shows a 3D convolution filter produces at least one output feature as a result of convolving over the sequence of per-cycle image patches on the sliding convolution window basis (Kostem [0158]).
Kostem does not explicitly specialist signal profilers for analyte classes and applying these specialist signal profilers to signals in respective signal profiles detected for analytes in respective analyte classes.
When combined with Kostem et al., Langlois et al. shows collecting data in a manner that leads to a partition of data where each image is associated with a tile to produce analyte classes which is used to produce per-cycle image patches (for a respective tile in which the data is associated with) for training convolution filters and utilizing convolution filters for a base calling operation with error adjustment associated with particular tiles. Langlois et al. shows a structure of two flow cells, each having two surfaces, with each surface having four lanes, each lane having six swaths, and each swath having 120 tiles in which data is collected, stored, and analyzed for each tile (Langlois et al. [0068] and [0069]). Langlois et al. shows base calling and error correction on a tile-by-tile basis (Langlois et al. [0068] and [0069]). The data collected, stored, and analyzed/error corrected for each tile leads to a partitioning of data that corrects for tile specific errors that may arise during sequencing.
Claim 2 is directed to wherein the respective analyte classes are representative of different spatial configurations of the analytes that contribute to creation of the respective signal profiles during the base calling operation.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which have a spatial configuration of analytes that contribute to the creation of a signal profile for a corresponding tile during a base calling operation (Langlois et al. [0068], [0069], and figure 3).
Claim 3 is directed to wherein the different spatial configurations include analytes being located on different surfaces of a biosensor on which the base calling operation is executed.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located on different surfaces (Langlois et al. [0068], [0069], and figure 3).
Claim 4 is directed to wherein the different surfaces include a top surface and a bottom surface. Claim 5 is directed to wherein the different spatial configurations include analytes being located on different lanes of the biosensor.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located on different surfaces such as a top surface or bottom surface with each surface containing four lanes (Langlois et al. [0068], [0069], and figure 3).
Claim 6 is directed to wherein the different spatial configurations include analytes being located on different lane groups of the biosensor. Claim 7 is directed to wherein the different lane groups include top peripheral lanes, central lanes, and bottom peripheral lanes. Claim 8 is directed to wherein the different lane groups include edge lanes and non-edge lanes.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located on different surfaces which include lane groups top peripheral lanes (i.e., lane 1 of flow cell 1 and flow cell 2), central lanes (i.e., lane 2 and 3 of flow cell 1 and flow cell 2), and bottom peripheral lanes (i.e., lane 4 of flow cell 1 and flow cell 2) and lane groups of edge lanes (i.e, lane 1 and lane 4 of the flow cells) and non-edge lanes (i.e., lane 2 and lane 3 of the flow cells) (Langlois et al. [0068], [0069], and figure 3).
Claim 9 is directed to wherein the different spatial configurations include analytes being located on different swathes of the different lanes of the biosensor. Claim 10 is directed to wherein the different swath groups include top peripheral swathes, central swathes, and bottom peripheral swathes. Claim 11 is directed to wherein the different swath groups include edge swathes and central swathes.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located on different surfaces which include different swathes of different lanes of the biosensor, where the swaths are located in locations of the flow cells such as top peripheral swaths, central swaths, bottom peripheral swaths, edge swaths, and non-edge swaths (Langlois et al. [0068], [0069], and figure 3).
Claim 12 is directed to wherein the different spatial configurations include analytes being located on different tiles of the different swathes of the different lanes of the biosensor.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located on different surfaces which include different swathes of different lanes of the biosensor (Langlois et al. [0068], [0069], and figure 3).
Claim 13 is directed to wherein the different spatial configurations include analytes being located on different tile groups of the biosensor. Claim 14 is directed to wherein the different tile groups include edge tiles, central tiles, and near-edge tiles.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located on different surfaces which include different tiles located edge tiles, central tiles, and near-edge tiles (Langlois et al. [0068], [0069], and figure 3).
Claim 15 is directed to wherein the different spatial configurations include analytes being located on different sub-tiles of the different tiles of the different swathes of the different lanes of the biosensor.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles which holds multiple clusters of analytes are located in different areas of the tiles (Langlois et al. [0068], [0069], and figure 3).
Claim 16 is directed to wherein the different spatial configurations include analytes being located on different sections of the biosensor. Claim 17 is directed to wherein the different sections include a top-right section, a top- central section, a top-left section, middle-right section, central section, middle-left section, bottom-left section, bottom-central section, and bottom-left section.
Kostem et al. in view of Langlois et al. shows the data collected corresponds to tiles which are located on different spatial locations of structure that has two flow cells (which is interpreted as a biosensor) and the analytes in these tiles are located in different sections of a biosensor such as a top-right section, a top-central section, a stop-left section, middle-right section, central section, middle-left section, bottom-left section, bottom-central section, and bottom-left section (Langlois et al. [0068], [0069], and figure 3).
Claim 18 is directed to wherein each specialist signal profiler is further trained to maximize signal-to-noise ratio of sequenced signals in a particular signal profile detected for analytes in a particular analyte sub-class and characterized in a particular training data sub-set, and wherein the runtime logic is further configured to execute the base calling operation by applying the respective specialist signal profilers to sequenced signals in respective signal profiles detected for analytes in respective analyte sub-classes during the base calling operation.
Kostem in view of Langlois et al. shows a 3D convolution filter convolve over - a plurality of the per-cycle image patches along a temporal dimension to detect and account for phasing and pre-phasing effect between successive ones of the sequencing cycles caused by asynchronous readout of sequence copies of an associated analyte within a convolution window (Kostem [0152]).
Claim 19 is directed to wherein the respective analyte sub-classes are representative of the different spatial configurations of the analytes that generated the sequenced signals at different temporal periods of the base calling operation, wherein different combinations of the different spatial configurations and the different temporal periods contribute to creation of the detected respective signal profiles during the base calling operation.
Kostem in view of Langlois et al. shows a 3D convolution filter convolve over - a plurality of the per-cycle image patches along a temporal dimension to detect and account for phasing and pre-phasing effect between successive ones of the sequencing cycles caused by asynchronous readout of sequence copies of an associated analyte within a convolution window which contains a sequence of per-cycle image batches which represent a different spatial configuration extracted from an image (Kostem [0152] and figure 4).
Claim 20 is directed to wherein the different temporal periods correspond to different sensing cycles in a series of sensing cycles of the base calling operation. Claim 21 is directed to wherein the different temporal periods correspond to different subseries of sensing cycles in the series of sensing cycles of the base calling operation.
Kostem in view of Langlois et al. shows different temporal periods corresponding to different sensing cycles of the base calling operation and further shows different temporal periods correspond to different subseries of sensing cycles (Kostem [0134] and figure 4).
Claim 22 is directed to wherein each specialist signal profiler is configured with channel- specific equalizers, wherein each channel-specific equalizer has a plurality of convolution kernels.
Kostem in view of Langlois et al. shows the 3D convolutions use imaged channel-specific convolution kernels (Kostem [0135]).
Claim 23 is directed to wherein the runtime logic is further configured to iteratively train the respective specialist signal profilers during the base calling operation. Claim 24 is directed to wherein, for a current training iteration, fitting data by optimizing parameters.
Kostem in view of Langlois et al. shows the optimization includes updating the coefficients/weights/parameters of the convolution kernels (and biases) of the 3D convolution filters to minimize the loss between the predicted base calls and the correct base calls identified by the ground truth with the loss being minimized using stochastic gradient descent with backpropagation (Kostem [0157]).
Claim 25 is directed to wherein the analytes correspond to wells when the biosensor is a patterned biosensor.
Kostem in view of Langlois et al. shows a patterned biosensor with wells which include analytes (Kostem [0075]).
Claim 26 is directed to wherein the sequenced signals are intensity signals.
Kostem in view of Langlois et al. shows that the input data of the sequenced signals may be intensity signals (Kostem et al. [0101]).
Claim 27 is directed to wherein the sequenced signals are voltage signals.
Kostem in view of Langlois et al. shows that the input data of the sequenced signals may be based on pH changes where the pH changes are detected and converted to a voltage change that is proportional to the number of bases incorporated (Kostem et al. [0102]).
Claim 28 is directed to wherein the sequenced signals are current signals.
Kostem in view of Langlois et al. shows that the input data of the sequenced signals may be electrical current signals derived from nucleotides passing through a membrane (Kostem et al. [0103]).
An invention would have been obvious to one or ordinary skill in the art if some motivation in the prior art would have led that person to combine reference teachings to arrive at the claimed invention. It would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have combined the 3D convolution filters that process per-cycle image patches by convolving over temporal dimensions to account for to detect and account for phasing and pre-phasing effect, convolving over a plurality of pixels in each of the per-cycle image patches along spatial dimensions to detect and account for spatial crosstalk, and convolving each of the imaged channels along a depth dimension to detect and account for emission overlap between the imaged channels of Kostem with the collecting, storing, and processing data on a tile-by-tile basis of a flow cell of Langlois et al. because this would give a system that collects data of a tile located in different locations of the flow cell and processes each tile data with 3D convolution filters (which are trained on per-image patches extracted from corresponding tiles) that accounts for phasing/pre-phasing, spatial-cross talk, and emission overlap on specific to a tile location on a flow cell and allows for real time processing of all tiles concurrently for each base calling cycle (Langlois et al. [0068]). One would have a reasonable expectation of success because Kostem shows convolution filters that process per-cycle image patches from image data while Langlois et al. shows collecting and storing tile image data which can be used to extract tile specific image patches to be processed on a tile-by-tile basis.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Belitz et al. (US 20180274023 A1; cited in IDS received 05 January 2023) in view of Kostem (US 20200364496 A1; cited in IDS received 05 January 2023).
Claim 31 is directed to a system, comprising: memory storing initially sequenced signals detected during initial sequencing cycles of a sequencing run for a population of analytes; fitting logic, having access to the memory, configured to process the initially sequenced signals on an analyte-by-analyte basis, to fit respective signal profiles for respective analytes in the population of analytes, and to store the respective signal profiles in the memory;
Belitz et al. shows fitting Gaussian distributions to a set of two-channel intensity data such that one distribution is applied for each of the four nucleotides represented in the data set (Belitz et al. [0153]).
online training logic, having access to the memory, configured to train respective specialist signal profilers in a plurality of specialist signal profilers to maximize signal-to-noise ratio of the respective signal profiles fitted for the respective analytes, and to store the trained respective specialist signal profilers in the memory;
Belitz et al. shows calculating a separate phasing correction for every tile at every cycle where the phasing correction for a given cycle is a mathematical formula for correcting intensity at a given cycle (Belitz et al. [0098]-[0100]). Belitz et el. shows numerically optimizing via a pattern search over phasing coefficients to maximize the mean chastity and once the phasing coefficient values are identified with maximal mean chastity, the phasing correction can be applied and then base calling can occur directly subsequent (Belitz et al. [0098]).
and runtime logic, having access to the memory, configured to uniquely map subsequently sequenced signals detected during subsequent sequencing cycles of the sequence run to the respective signal profiles on the analyte-by-analyte basis, and to apply the trained respective specialist signal profilers to the subsequently sequenced signals based on the unique mapping to the respective signal profiles to generate base calls for the subsequent sequencing cycles on the analyte-by-analyte basis.
Belitz et al. shows an EM algorithm that for X and Y intensity values (referring to each of the two channel intensities respectively) a value can be generated which represents the likelihood that certain X, Y intensity value belongs to one of the four distributions which is interpreted as mapping signals to respective signal distributions (Belitz et al. [0154]). Belitz et al. shows applying phasing correction (specialist signal profiler) then performing base calling (Belitz et al. [0098]).
Belitz et al. does not show signal profiles for respective analytes in the population of analytes or processing on an analyte-by-analyte basis.
Like Belitz et al., Kostem shows measuring intensity data from base incorporation events for base calling with error correction. Kostem shows a sensor on a sample surface configured to receive light emissions from at least two clusters (a population of analytes) where the intensity of respective light emissions for the two clusters is significantly different such that one of the two clusters is a “bright” cluster and the other is a “dim” cluster (Kostem [0106]-[0111]). Kostem shows the ability to identify these clusters based on intensity data measured and use a base calling algorithm to classify pixel signals from the bright and dim clusters into one of sixteen distributions which is interpreted as processing on an analyte-by-analyte basis (Kostem [0106]-[0111]).
An invention would have been obvious to one or ordinary skill in the art if some motivation in the prior art would have led that person to modify reference teachings to arrive at the claimed invention. It would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the system which processes intensity values of an image data collected from base incorporation events to perform base calling with correction of phasing errors of Belitz et al. with the ability to distinguish between bright and dim clusters in intensity data from light emissions from at least two cluster of Kostem because this would allow for a system that can distinguish between two clusters based on intensity data of light emissions and performing base calling (with phasing error correction) on two clusters concurrently (Kostem [0110]-[0111]). One would have a reasonable expectation of success because Belitz et al. shows processing intensity data to perform base calling with error correction while Kostem shows intensity data of a bright and dim cluster with the ability to distinguish between these clusters and performing base calling on these clusters.
Conclusion
No claims are allowed.
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONATHAN EDWARD HAYES whose telephone number is (571)272-6165. The examiner can normally be reached M-F 9am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at 571-272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.E.H./Examiner, Art Unit 1685
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685