DETAILED ACTION
The Applicant’s filing, received 29 December 2022, has been fully considered. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
The preliminary amendment received 25 April 2023 has been entered.
Claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are pending.
Claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are rejected.
Priority
This application is a CON of PCT/US2021/040165, filed 01 July 2021,
which claims benefit of 63/047,896, filed 02 July 2020.
Therefore, the effective filing date of the claimed invention is 02 July 2020.
Information Disclosure Statement
The information disclosure statements (IDS) received 28 February 2023 and 22 May 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
The listing of references in the specification (e.g., see at least paras. [0035], [0044] & [0114]) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings received 29 December 2022 are objected to, as noted below.
The drawings are objected to as failing to comply with 37 CFR 1.84(t) because:
The sheets of drawings should be numbered in consecutive Arabic numerals, starting with 1, within the sight as defined in paragraph (g) of this section, and the number of each sheet should be shown by two Arabic numerals placed on either side of an oblique line, with the first being the sheet number and the second being the total number of sheets of drawings, with no other marking.
The drawings are further objected to as failing to comply with 37 CFR 1.84(p)(5) because:
Reference characters not mentioned in the description shall not appear in the drawings, e.g.,
reference #’s 335 and 340 in Fig. 3; and
reference #’s 1302, 1312, and 1316 in Fig. 14.
The drawings are further objected to as failing to comply with 37 CFR 1.84(p)(5) because:
Reference characters mentioned in the description must appear in the drawings, e.g.,
the specification at para. [0165] describes reference #’s 1400, 1402, 1404, 1406, 1408, 1410, 1412, 1414, and 1416, however these reference #’s do not appear in the drawings.
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.
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 limitation(s) are:
a data store configured to store, in claim 21;
a unique molecule filtering engine configured to, in claims 21, 31;
upstream processing engines configured to, in claim 31; and
downstream processing engines configured to, in claim 32.
Because these claim limitation(s) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The written description discloses a corresponding structure for the generic placeholder(s):
a data store configured to store, in claim 21, at paras. [0163] & [0164] (e.g., a computer-readable medium);
a unique molecule filtering engine configured to, in claims 21, 31, and 32, and 32, at paras. [0123] – [0127] & Fig. 4 (e.g., algorithm) and at para. [0168] (e.g., software that is executed by a processor);
upstream processing engines configured to, in claim 31, at para. [0142] (e.g., algorithms) and at para. [0168] (e.g., software that is executed by a processor); and
downstream processing engines configured to, in claim 32, at para. [0150] (e.g., algorithms) and at para. [0168] (e.g., software that is executed by a processor).
If applicant does not intend to have 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 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 them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Objections
Applicant is advised that should claim 10 be found allowable, claim 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. Both claims provide the same limitations and depend on claim 1.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the total recovered cell count" in line five. There is insufficient antecedent basis for this limitation in the claim, because the claim previously recites “an expected total recovered cell count,” and therefore it is not clear as to whether these limitations are referring to the same cell count.
Claims 2, 5, 7, 9, and 10 are indefinite for depending from claim 1 and for failing to remedy the indefiniteness of claim 1.
Claim 11 recites the limitation "the total recovered cell count" in lines six and seven. There is insufficient antecedent basis for this limitation in the claim, because the claim previously recites “an expected total recovered cell count,” and therefore it is not clear as to whether these limitations are referring to the same cell count.
Claims 12, 15, 17, 19, and 20 are indefinite for depending from claim 11 and for failing to remedy the indefiniteness of claim 11.
Claim 21 recites the limitation "the total recovered cell count" in line ten. There is insufficient antecedent basis for this limitation in the claim, because the claim previously recites “an expected total recovered cell count,” and therefore it is not clear as to whether these limitations are referring to the same cell count.
Claims 22, 25, 27, and 29-32 are indefinite for depending from claim 21 and for failing to remedy the indefiniteness of claim 21.
Claim 1 is further indefinite for reciting “fitting the barcode dataset to a model” in line thirteen, because it is not clear as to whether the barcode dataset at the “fitting the barcode dataset to a model” step is the same data as the barcode dataset at line three, or if the barcode dataset at the “fitting… to a model” step is an updated barcode dataset based on the “determining a region of interest…” step at line five.
Claims 2, 5, 7, 9, and 10 are indefinite for depending from claim 1 and for failing to remedy the indefiniteness of claim 1.
Claim 11 is further indefinite for reciting “fitting… the barcode dataset to a model” in line fifteen, because it is not clear as to whether the barcode dataset at the “fitting… the barcode dataset to a model” step is the same data as the barcode dataset at line five, or if the barcode dataset at the “fitting… the barcode dataset to a model” step is an updated barcode dataset based on the “determining… a region of interest…” step at line six.
Claims 12, 15, 17, 19, and 20 are indefinite for depending from claim 11 and for failing to remedy the indefiniteness of claim 11.
Claim 21 is further indefinite for reciting “fit the barcode dataset to a model” in line seventeen, because it is not clear as to whether the barcode dataset at the “fit the barcode dataset to a model” step is the same data as the barcode dataset at line eight, or if the barcode dataset at the “fit the barcode dataset to a model” step is an updated barcode dataset based on the “determine a region of interest…” step at line ten.
Claims 22, 25, 27, and 29-32 are indefinite for depending from claim 21 and for failing to remedy the indefiniteness of claim 21.
Claim 2 recites the limitation "the 1st percentile barcode of ranked barcodes" in lines one and two. There is insufficient antecedent basis for this limitation in the claim, because claim 1 only recites “a percentile,” ans does not recite a “1st percentile barcode.”
Claim 12 recites the limitation "the 1st percentile barcode of ranked barcodes" in lines one and two. There is insufficient antecedent basis for this limitation in the claim, because claim 11 only recites “a percentile,” and does not recite a “1st percentile barcode.”
Claim 22 recites the limitation "the 1st percentile barcode of ranked barcodes" in lines one and two. There is insufficient antecedent basis for this limitation in the claim, because claim 21 only recites “a percentile,” but does not recite a “1st percentile barcode.”
Claim 10 recites the limitations “the curve" and “the first derivative” in line two. There is insufficient antecedent basis for these limitations in the claim, because claim 1 does not recite a curve or a first derivative.
Claim 20 recites the limitations “the curve" and “the first derivative” in line two. There is insufficient antecedent basis for these limitations in the claim, because claim 1 does not recite a curve or a first derivative.
Claim 30 recites the limitations “the curve" and “the first derivative” in line two. There is insufficient antecedent basis for these limitations in the claim, because claim 21 does not recite a curve or a first derivative.
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, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite: (a) mathematical concepts, (e.g., mathematical relationships, formulas or equations, mathematical calculations); and (b) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgement, opinion).
Subject matter eligibility evaluation in accordance with MPEP 2106.
Eligibility Step 1: Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter?
Claims 1, 2, 5, 7, 9, and 10 recite a method for identifying a subset of cells from a dataset (i.e., a process); claims 11, 12, 15, 17, 19, and 20 recite a non-transitory computer readable medium (i.e., a machine and/or a manufacture); and claims 21, 22, 25, 27, and 29-32 recite a system comprising a computing device communicatively connected to a data store (i.e., a machine and/or a manufacture).
Therefore, these claims are encompassed by the categories of statutory subject matter, and thus, satisfy the subject matter eligibility requirements under step 1.
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two whether the recited judicial exception is integrated into a practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception, examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
Independent claim 1 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
defining an expected total recovered cell count for a barcode dataset, wherein the barcodes in the dataset are sorted based on count (i.e., mental processes and mathematical concepts);
determining a region of interest for the total recovered cell count by
(a) calculating a lower bound for the region of interest using a percentile of the sorted barcodes, wherein all barcodes having a molecule count above the lower bound are included for further analysis (i.e., mental processes and mathematical concepts);
(b) calculating an upper bound for the region of interest by including an additional subset of barcodes having molecule counts below the lower bound, wherein each barcode in the subset that has a molecule count below a count threshold is excluded from further analysis (i.e., mental processes and mathematical concepts);
fitting the barcode dataset to a model, wherein the model groups barcodes as a function of molecule count (i.e., mental processes and mathematical concepts);
identifying a cut-off value on the model, wherein all barcodes having a molecule count above the cut-off value are called as cells (i.e., mental processes and mathematical concepts); and
identifying a targeted subset of cells from the called cells for conducting targeted gene expression, wherein a cell qualifies as part of the targeted subset if the cell has a molecule count above a target threshold (i.e., mental processes and mathematical concepts).
Independent claim 11 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
defining an expected total recovered cell count for a barcode dataset, wherein the barcodes in the dataset are sorted based on count (i.e., mental processes and mathematical concepts);
determining a region of interest for the total recovered cell count by
(a) calculating a lower bound for the region of interest using a percentile of the sorted barcodes, wherein all barcodes having a molecule count above the lower bound are included for further analysis (i.e., mental processes and mathematical concepts);
(b) calculating an upper bound for the region of interest by including an additional subset of barcodes below the lower bound, wherein each barcode in the subset that has a molecule count below a count threshold is excluded from further analysis (i.e., mental processes and mathematical concepts);
fitting the barcode dataset to a model, wherein the model groups barcodes as a function of molecule count (i.e., mental processes and mathematical concepts);
identifying a cut-off value on the model, wherein all barcodes having a molecule count above the cut-off value are called as cells (i.e., mental processes and mathematical concepts); and
identifying a targeted subset of cells from the called cells for conducting targeted gene expression, wherein a cell qualifies as part of the targeted subset if the cell has a molecule count above a target threshold (i.e., mental processes and mathematical concepts).
Independent claim 21 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
define an expected total recovered cell count for a barcode dataset, wherein the barcodes in the dataset are sorted based on count (i.e., mental processes and mathematical concepts);
determine a region of interest for the total recovered cell count by
(a) calculating a lower bound for the region of interest using a percentile of the sorted barcodes, wherein all barcodes having a molecule count above the lower bound are included for further analysis (i.e., mental processes and mathematical concepts); and
(b) calculating an upper bound for the region of interest by including an additional subset of barcodes below the lower bound, wherein each barcode in the subset that has a molecule count below a count threshold is excluded from further analysis (i.e., mental processes and mathematical concepts);
fit the barcode dataset to a model, wherein the model groups barcodes as a function of molecule count (i.e., mental processes and mathematical concepts);
identify a cut-off value on the model, wherein all barcodes having a molecule count above the cut-off value are called as cells (i.e., mental processes and mathematical concepts); and
identify a targeted subset of cells from the called cells for conducting targeted gene expression, wherein a cell qualifies as part of the targeted subset if the cell has a molecule count above a target threshold (i.e., mental processes and mathematical concepts).
Dependent claims 2, 5, 7, 9, 10, 12, 15, 17, 19, 20, 22, 25, 27, and 29-32 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claim 2 further recites:
the percentile is the 1st percentile barcode of ranked barcodes (i.e., mental processes and mathematical concepts).
Dependent claim 5 further recites:
the count threshold is about 10 counts (i.e., mental processes and mathematical concepts).
Dependent claim 7 further recites:
the model is a plot of count as a function of ranked barcodes (i.e., mental processes and mathematical concepts).
Dependent claim 9 further recites:
the cut-off value on the model is determined by a mathematical method selected from the group consisting of a cubic spline curve fitted to a log-transformed barcode-rank plot, linear regression analysis, non-linear regression analysis, probability distribution fitting, smoothing, interpolation methods, trend estimation, least-squares estimation, function approximation, Loess fitting, and combinations thereof (i.e., mental processes and mathematical concepts).
Dependent claim 10 further recites:
the cut-off value is the point on the curve where the first derivative reaches a global minimum value (i.e., mental processes and mathematical concepts).
Dependent claim 12 further recites:
the percentile is the 1st percentile barcode of ranked barcodes (i.e., mental processes and mathematical concepts).
Dependent claim 15 further recites:
the count threshold is about 10 counts (i.e., mental processes and mathematical concepts).
Dependent claim 17 further recites:
the model is a plot of count as a function of ranked barcodes (i.e., mental processes and mathematical concepts).
Dependent claim 19 further recites:
the cut-off value on the model is determined by a mathematical method selected from the group consisting of a cubic spline curve fitted to a log-transformed barcode-rank plot, linear regression analysis, non-linear regression analysis, probability distribution fitting, smoothing, interpolation methods, trend estimation, least-squares estimation, function approximation, Loess fitting, and combinations thereof (i.e., mental processes and mathematical concepts).
Dependent claim 20 further recites:
the cut-off value is the point on the curve where the first derivative reaches a global minimum value (i.e., mental processes and mathematical concepts).
Dependent claim 22 further recites:
the percentile is the 1st percentile barcode of ranked barcodes (i.e., mental processes and mathematical concepts).
Dependent claim 25 further recites:
the count threshold is about 10 counts (i.e., mental processes and mathematical concepts).
Dependent claim 27 further recites:
the model is a plot of count as a function of ranked barcodes (i.e., mental processes and mathematical concepts).
Dependent claim 29 further recites:
the cut-off value on the model is determined by a mathematical method selected from the group consisting of a cubic spline curve fitted to a log-transformed barcode-rank plot, linear regression analysis, non-linear regression analysis, probability distribution fitting, smoothing, interpolation methods, trend estimation, least-squares estimation, function approximation, Loess fitting, and combinations thereof (i.e., mental processes and mathematical concepts).
Dependent claim 30 further recites:
the cut-off value is the point on the curve where the first derivative reaches a global minimum value (i.e., mental processes and mathematical concepts).
Dependent claim 31 further recites:
one or more upstream processing engines configured to process the genomic sequence data set prior to being received by the unique molecule filtering engine (i.e., mental processes).
Dependent claim 32 further recites:
one or more downstream processing engines configured to process the identified targeted subset of cells generated by the unique molecule filtering engine (i.e., mental processes).
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pen and paper (e.g., defining an expected total recovered cell count for a barcode dataset, wherein the barcodes in the dataset are sorted based on count), and therefore recite judicial exceptions from the mental process grouping of abstract ideas. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas (e.g., calculating a lower bound for the region of interest using a percentile of the sorted barcodes, wherein all barcodes having a molecule count above the lower bound are included for further analysis) are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Therefore, claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 recite an abstract idea.
[Step 2A Prong One: YES]
Eligibility Step 2A Prong Two: In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea 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 abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)(III)).
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
Independent claim 1 and dependent claims 2, 5, 7, 9, 10, 12, 15, 17, 19, 20, 22, 25, 27, and 29-32 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional elements in independent claim 11 include:
a non-transitory computer-readable medium storing computer instructions; and
one or more processors.
The additional elements in independent claim 21 include:
a data store (i.e., a database); and
a computing device communicatively connected to the data store.
The additional elements of a non-transitory computer-readable medium storing computer instructions (claim 11); one or more processors (claim 11); a database (claim 21); and a computing device communicatively connected to the database (claim 21); invoke a computer and/or computer-related components merely as tools for use in the claimed process, such that they amount to no more than mere instructions to apply the exceptions using a generic computer (MPEP 2106.05(f)), and therefore are not an improvement to computer functionality itself, or an improvement to any other technology or technical field, and thus, do not integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(1)).
Thus, the additionally recited elements merely invoke a computer and/or computer related components as tools, and/or amount to no more than mere instructions to apply the exceptions using a generic computer; and as such, when all limitations in claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 have been considered as a whole (i.e., the analysis takes into consideration all the claim limitations and how those limitations interact and impact each other when evaluating whether the exception is integrated into a practical application), the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are directed to an abstract idea (MPEP 2106.04(d)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. 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 amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
Independent claim 1 and dependent claims 2, 5, 7, 9, 10, 12, 15, 17, 19, 20, 22, 25, 27, and 29-32 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 11 and 21 are identified above, and carried over from Step 2A Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of a non-transitory computer-readable medium storing computer instructions (claim 11); one or more processors (claim 11); a database (claim 21); and a computing device communicatively connected to the database (claim 21); are conventional computer components and/or functions (see MPEP at 2106.05(b) and 2106.05(d)(II) regarding conventionality of computer components and computer processes).
Therefore, when taken alone (i.e., individually), all additional elements in claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as an ordered combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (“Massively parallel digital transcriptional profiling of single cells.” Nature Communications, 2017, vol. 8:14049, pp. 1-12, with Supplementary Material, unnumbered pages 13-30; (Zheng et al. as cited in the Information Disclosure Statement received 28 February 2023 was not considered because the reference did not include the Supplementary Material)) and Zhang et al. (“Comparative Analysis of Droplet-Based Ultra-High-Throughput Single-Cell RNA-Seq Systems,” Molecular Cell, 2019, vol. 73, pp. 130-142, as cited in the Information Disclosure Statement received 28 February 2023) and Lun et al. (“EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data.” Genome Biology, 2019, vol. 20:63, pp. 1-9, with Supplementary Material, pages 1-21).
Independent claims 1, 11, and 21 are directed to a method, a non-transitory computer-readable medium storing computer instructions, and a system for identifying a subset of cells from a genomic sequence dataset based on detecting cell-associated barcodes. It is noted that the specification provides that : [0051] The term "barcode," as used herein, generally refers to a label, or identifier, that conveys or is capable of conveying information about an analyte.’’ which can then include informative portions of the target sequence itself as conveying information.
Dependent claims 2, 5, 7, 9, 10, 12, 15, 17, 19, 20, 22, 25, 27, and 29-32 further define the steps in the computational algorithm.
Zheng et al. is directed to a droplet-based system that enables 3’ mRNA counting of tens of thousands of single cells per sample.
Zhang et al. is directed to a comparative analysis of droplet-based ultra-high-throughput single-cell RNA-seq systems, including three prevalent droplet-based systems, namely, inDrop, Drop-seq, and 10X Genomics Chromium (10X) (page 132, col. 1, para. 2).
Lun et al. is directed to a statistical method for calling cells from droplet-based data that is more recent than the systems described by Zhang et al. and Zheng et al.
Regarding independent claims 1, 11, and 12, Zheng et al. shows a droplet-based system that enables 3’ messenger RNA (mRNA) digital counting of thousands of single cells (page 2, col. 1, para. 2); after a read alignment step, filtering barcodes (and UMIs (i.e., unique molecular identifiers) and generating a gene-barcode matrix for further analysis (page 2, col. 2, para. 2); based on the distribution of total UMI counts for each barcode, estimating the number of GEMs (i.e., Gel bead in EMulsion) that contained cells (page 2, col. 2, para. 3) and expected and observed number of cells per GEM (Supplementary Figure 1); a pipeline workflow showing the counting of UMIs (by cell, gene) and selecting cell-associated barcodes to generate a gene-barcode matrix (Figure 1(f)); mean observed UMI counts for each molecule compared with the expected number of molecules per GEM, with a straight line fitted to the data (i.e., a model) to summarize the relationship (Figure 2(d)); a single-cell software suite for sample demultiplexing, barcode processing, and single-cell 3’ gene counting (page 10, col. 2, para. 1); filtering barcodes and UMIs (page 10, col. 2, para. 2); using a sequencing quality score of >10 as a threshold for validity (page 10, col. 2, para. 3); cell barcodes were determined based in distribution of UMI counts, where all top barcodes within the same order of magnitude (>10% of the top nth barcode, where n is 1% of the expected recovered cell count) were considered cell barcodes (page 10, col. 2, para. 5); and identification of cluster-specific genes (page 11, col. 1, para. 3; and Supplementary Figure 3).
Regarding independent claims 1, 11, and 12, Zheng et al. does not explicitly show using count thresholds and target thresholds for molecule counts, or cut-off values.
Regarding independent claims 1, 11, and 12, Zhang et al. shows performing cell barcode filtering based on the total count of UMIs (transcripts) and using a total UMI cutoff value of 1,000 as a filter for which cell barcodes are compared to (page 135, (bottom).
Regarding independent claims 1, 11, and 12, Lun et al. shows a method for calling cells from droplet-based data, based on detecting significant deviations from the expression profile of the ambient solution, and that retains distinct cell types that would have been discard by existing methods (Abstract); using a knee point filter to ensure that barcodes with large total counts are always retained (page 2, col. 1, para. 2); using a knee point in a function that corresponds to a transition between a distinct subset of barcodes with large totals and the majority of barcodes with smaller totals (page 3, col. 1, para. 3); and defining upper and lower thresholds using knee points to determine whether barcodes are retained (page 3, col. 2, paras. 1 and 2).
Regarding dependent claims 2, 12, and 22, Zheng et al. does not explicitly show that the percentile is the 1st percentile barcode of ranked barcodes, however Zheng et al. does explicitly show that all top barcodes within the same order of magnitude (>10% of the top nth barcode, where n is 1% of the expected recovered cell count) were considered cell barcodes (page 10, col. 2, para. 5).
Regarding dependent claims 5, 15, and 25, Lun et al. does not explicitly show a count threshold is about 10 counts, but does show retaining barcodes with total counts above a knee point threshold (and therefore excluding barcodes with a molecule count below the threshold) (page 8, col. 1, para. 3).
Regarding dependent claims 7, 17, and 27, Lun et al. further shows a barcode rank plot showing the fitted spline used for knee point detection (Supplementary Material, page 18, Fig. S14).
Regarding dependent claims 9, 19, and 29, Lun et al. further shows a barcode rank plot showing the fitted spline used for knee point detection (Supplementary Material, page 18, Fig. S14).
Regarding dependent claims 10, 20, and 30, Zhang et al. further shows generating the derivation of the plot of log-transformed barcode rank and barcode reads (page e3, para. 2) (i.e., the derivation of a plot of log-transformed rank can represent a first derivative).
Regarding dependent claims 31 and 32, Zheng et al. further shows a pipeline workflow with various steps upstream and downstream of counting and selecting cell-associated barcodes (Figure 1(f)).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Zheng et al. by incorporating methods for performing cell barcode filtering based on the total count of UMIs (transcripts) and using a total UMI cutoff value, as shown by Zhang et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Zheng et al. with the methods of Zhang et al., because Zhang et al. shows methods for utilizing filtering and cut-off values to remove invalid cell barcodes. This modification would have had a reasonable expectation of success given that both Zheng et al. and Zhang et al. disclose methods for detecting cell-associated barcodes from single-cell partitions.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method shown by Zheng et al. by incorporating methods for defining upper and lower thresholds using knee points to determine whether barcodes are retained, as shown by Lun et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Zheng et al. with the methods of Lun et al., because Lun et al. shows a method for calling cells from droplet-based data, based on detecting significant deviations from the expression profile of the ambient solution, and that retains distinct cell types that would have been discard by existing methods. This modification would have had a reasonable expectation of success given that both Zheng et al. and Lun et al. disclose methods for detecting cell-associated barcodes from single-cell partitions.
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, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/090,903 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the reference application claims are both directed to analyzing barcode data of barcodes that are associated with sequence read data in order to determine whether a given barcode is in fact associated with an actual molecule. Furthermore, the instant claims and the reference application claims both utilize thresholds to filter the sequence read data according to the barcode identifiers in order to determine if there is an actual molecule count associated with the barcode identifier.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 application.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN W. BAILEY whose telephone number is (571)272-8170. The examiner can normally be reached Mon - Fri. 1000 - 1800.
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, KARLHEINZ SKOWRONEK can be reached at (571) 272-9047. 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.
/S.W.B./Examiner, Art Unit 1687
/Joseph Woitach/Primary Examiner, Art Unit 1687
Prosecution Insights