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
Claims 1-24 are pending.
Claims 1-24 are rejected.
Priority
This application is a CON of PCT/US2021/040181, filed 01 July 2021,
which claims benefit of 63/047,891, filed 02 July 2020.
Therefore, the effective filing date of the claimed invention is 02 July 2020.
Information Disclosure Statement
The information disclosure statement (IDS) received 23 May 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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.
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 limitations are:
a data store configured to store, in claim 11;
a unique molecule filtering engine configured to, in claim 11;
upstream processing engines configured to, in claim 20;
downstream processing engines configured to, claim 21.
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 11, at paras. [001243] & [00144] (e.g., a computer-readable medium such as a hard disk);
a unique molecule filtering engine configured to, in claim 11, at para. [0091] (e.g., algorithms) and para. [00148] (e.g., a software program and applications written in conventional programming languages and executed by a processor);
upstream processing engines configured to, in claim 20, at para. [00123] (e.g., algorithms) and para. [00148] (e.g., a software program and applications written in conventional programming languages and executed by a processor);
downstream processing engines configured to, claim 21, at para. [00132] (e.g., algorithms) and para. [00148] (e.g., a software program and applications written in conventional programming languages and executed by a processor); and
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 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 1-24 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 1-9 recite a method for filtering out erroneous sequence reads from a genomic sequence dataset (i.e., a process); claim 10 recites a non-transitory computer-readable medium in which a program is stored (i.e., a machine or a manufacture); and claims 11-24 recites a system comprising a computing device communicatively connected to a data store (i.e., a machine 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:
determining a threshold value for filtering out select fragment sequence reads from the genomic sequence dataset (i.e., mental processes and mathematical concepts),
wherein the threshold value is a number of fragment sequence reads in the genomic sequence dataset with the same unique identifier sequence (i.e., mental processes and mathematical concepts);
filtering fragment sequence reads with the same unique identifier sequence occurring at less than the threshold value in the genomic sequence dataset (i.e., mental processes and mathematical concepts); and
generating a filtered genomic sequence dataset (i.e., mental processes).
Independent claim 10 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
determining a threshold value for filtering out select fragment sequence reads from the genomic sequence dataset (i.e., mental processes and mathematical concepts),
wherein the threshold value is a number of fragment sequence reads in the genomic sequence dataset with the same unique identifier sequence (i.e., mental processes and mathematical concepts);
filtering fragment sequence reads with the same unique identifier sequence occurring at less than the threshold value in the genomic sequence dataset (i.e., mental processes and mathematical concepts); and
generating a filtered genomic sequence dataset (i.e., mental processes).
Independent claim 11 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
a unique molecule filtering engine configured to:
determine a threshold value for filtering out select fragment sequence reads from the genomic sequence dataset (i.e., mental processes and mathematical concepts),
wherein the threshold value is a number of fragment sequence reads in the genomic sequence dataset with the same unique identifier sequence (i.e., mental processes and mathematical concepts), and
filter fragment sequence reads with the same unique identifier sequence occurring at less than the threshold value in the genomic sequence dataset (i.e., mental processes and mathematical concepts), and
generate a filtered genomic sequence dataset (i.e., mental processes).
Dependent claims 2-9 and 12-21 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 threshold value is a product of a dynamic quantile modifier derived from the genomic sequence dataset and a pre-set multiplier (i.e., mental processes and mathematical concepts).
Dependent claim 3 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 90th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 4 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 95th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 5 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 75th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 6 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 50th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 7 further recites:
the pre-set multiplier is between about 0.005 and about 0.05 (i.e., mental processes and mathematical concepts).
Dependent claim 8 further recites:
the pre-set multiplier is between about 0.025 and about 0.1 (i.e., mental processes and mathematical concepts).
Dependent claim 9 further recites:
the pre-set multiplier is between about 0.001 and about 0.5 (i.e., mental processes and mathematical concepts).
Dependent claim 12 further recites:
the threshold value is a product of a dynamic quantile modifier derived from the genomic sequence dataset and a pre-set multiplier (i.e., mental processes and mathematical concepts).
Dependent claim 13 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 90th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 14 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 95th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 15 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 75th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 16 further recites:
the dynamic quantile modifier is a number of fragment sequence reads registered at a greater than a 50th percentile rank of a frequency distribution plot of fragment sequence reads with a same unique identifier sequence found in the genomic sequence dataset (i.e., mental processes and mathematical concepts).
Dependent claim 17 further recites:
the pre-set multiplier is between about 0.005 and about 0.05 (i.e., mental processes and mathematical concepts).
Dependent claim 18 further recites:
the pre-set multiplier is between about 0.025 and about 0.1 (i.e., mental processes and mathematical concepts).
Dependent claim 19 further recites:
the pre-set multiplier is between about 0.001 and about 0.5 (i.e., mental processes and mathematical concepts).
Dependent claim 20 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 21 further recites:
one or more downstream processing engines configured to process the filtered genomic sequence data set 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., generating a filtered genomic sequence dataset), 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., determining a threshold value for filtering out select fragment sequence reads from the genomic sequence dataset, wherein the threshold value is a number of fragment sequence reads in the genomic sequence dataset with the same unique identifier sequence) are abstract ideas.
Therefore, claims 1-24 recite an abstract idea and also mathematical concepts.
[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.
Dependent claims 2-9 and 12-21 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 1 include:
one or more processors; and
receiving the genomic sequence dataset, wherein the dataset comprises a plurality of fragment sequence reads, each with an associated barcode sequence and a unique identifier sequence (i.e., receiving data).
The additional elements in independent claim 10 include:
one or more processors;
a non-transitory computer-readable medium in which a program is stored; and
receiving the genomic sequence dataset, wherein the dataset comprises a plurality of fragment sequence reads, each with an associated barcode sequence and a unique identifier sequence (i.e., receiving data).
The additional elements in independent claim 11 include:
a data store configured to store the genomic sequence dataset comprising a plurality of fragment sequence reads, each with an associated barcode sequence and a unique identifier sequence;
a computing device communicatively connected to the data store; and
receive the genomic sequence dataset (i.e., receive data).
The additional elements in dependent claims 22-24 include:
the data store and the computing device are part of an integrated apparatus (claim 22);
the data store is hosted by a different device than the computing device (claim 23); and
the data store and the computing device are part of a distributed network system (claim 24).
The additional elements of one or more processors (claims 1 and 10); a non-transitory computer-readable medium in which a program is stored (claim 10); a data store configured to store the genomic sequence dataset comprising a plurality of fragment sequence reads, each with an associated barcode sequence and a unique identifier sequence (claim 11); a computing device communicatively connected to the data store (claim 11); the data store and the computing device are part of an integrated apparatus (claim 22); the data store is hosted by a different device than the computing device (claim 23); and the data store and the computing device are part of a distributed network system (claim 24); 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)).
The additional elements of receiving the genomic sequence dataset, wherein the dataset comprises a plurality of fragment sequence reads, each with an associated barcode sequence and a unique identifier sequence (i.e., receiving data) (claims 1 and 10); and receive the genomic sequence dataset (i.e., receive data) (claim 11); are merely a pre-solution activity of gathering data for use in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
Thus, the additionally recited elements merely invoke a computer and/or computer related components as tools; and/or amount to insignificant extra-solution activity; and as such, when all limitations in claims 1-24 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 1-24 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.
Dependent claims 2-9 and 12-21 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 1, 10, and 11 and dependent claims 22-24 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 one or more processors (claims 1 and 10); a non-transitory computer-readable medium in which a program is stored (claim 10); a data store configured to store the genomic sequence dataset comprising a plurality of fragment sequence reads, each with an associated barcode sequence and a unique identifier sequence (claim 11); a computing device communicatively connected to the data store (claim 11); the data store and the computing device are part of an integrated apparatus (claim 22); the data store is hosted by a different device than the computing device (claim 23); the data store and the computing device are part of a distributed network system (claim 24); and receiving data (claims 1, 10, and 11); 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 1-24 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 1-24 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 § 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 1, 10, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Parekh et al. (“zUMIs – A fast and flexible pipeline to process RNA sequencing data with UMIs.” GigaScience, 2018, vol. 7, pp. 1-9).
Independent claims 1, 10, and 11 are directed to a method, a computer-readable medium in which a program is stored, and a system, respectively, for using a threshold value for filtering out erroneous sequence reads from a genomic sequence dataset.
Parekh et al. is directed to a bioinformatics pipeline for scRNA-seq data that efficiently tabulates reads according to both sample-specific barcodes (BCs) and unique molecular identifiers (UMIs).
Regarding independent claims 1, 10, and 11, Parekh et al. shows receiving a sequence read dataset wherein the reads contain barcodes and unique molecular identifiers (page 7, col. 1, para. 3); filtering reads that have low quality BCs and UMIs according to a user-defined threshold eliminate the majority of spurious BCs and UMIs to generate a filtered dataset (page 2, col. 2, para. 1; and Table 1).
Therefore, Parekh et al. anticipates instant claims 1, 10, and 11.
Claim Rejections - 35 USC § 103
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 1-24 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, and Supplementary Material, unnumbered pages 1-18 (lined out and not considered in the IDS received 23 May 2023 because the reference did not include the Supplementary Material)) and Romanov et al. (“Molecular design of hypothalamus development.” Nature, 2020, vol. 582, pp. 246-252, and Methods, unnumbered pages 1-23, and Supplementary Information, numbered pages 1-12).
Independent claims 1, 10, and 11 are directed to a method, a computer-readable medium in which a program is stored, and a system, respectively, for using a threshold value for filtering out erroneous sequence reads from a genomic sequence dataset.
Dependent claims 2-9 and 12-24 further define the criteria for determining the threshold value for filtering out select reads from the dataset.
Zheng et al. is directed to a method for characterizing the transcriptome of individual cells by the counting of tens of thousands of single cells per sample.
Romanov et al. is directed to identifying molecular principles that shape the developmental architecture of the hypothalamus by using various datasets including single-cell RNA sequencing data for deriving unique molecular count (UMI) expression matrices.
Regarding independent claims 1, 10, and 11, Zheng et al. shows a bioinformatics pipeline workflow (Figure 1(f)) that begins with receiving data from a scRNA-seq workflow on a GemCode technology platform that culminates in generating sequencing read data (Figure 1(a)), wherein the sequence read data is generated from finished library molecules consisting of barcodes and unique molecular identifiers (UMIs) (Figure 1(e)); filtering barcodes and UMIs, wherein UMIs with sequencing quality score >10 were considered valid (page 10, col. 2, paras. 2-3); and generating a gene-barcode matrix as an output of the pipeline (Figure 1(f)).
Regarding independent claims 1, 10, and 11, Zheng et al. does not explicitly show using threshold values for filtering out select sequence reads.
Regarding independent claims 1, 10, and 11, Romanov et al. shows using threshold values, e.g., on “Quality score” vs. “Cell rank” plots (Supplementary Information, Supplementary Figure S5 and Note, pages 3-4; and Methods, unnumbered page 1, col. 2, para. 3).
Regarding dependent claims 2-9 and 12-19, Romanov et al. does not show the particular metric of deriving a threshold value as being a product of a dynamic quantile modifier (i.e., a number of fragment reads registered at a particular percentile rank of a frequency distribution plot) and a pre-set multiplier (i.e., a value inversely correlated with the dynamic quantile modifier, however, Romanov et al. does show using a corrected matrix with cells that passed filters of two different software programs and also possessing ‘high-quality’ label (upper quartile) together with all cells above the 90th percentile of quality score (Methods, unnumbered page 1, col. 2, para. 4; and Supplementary Information, Supplementary Figure S5 and Note, pages 3-4). Romanov et al. further shows a frequency distribution of reads, e.g., on “# Reads” vs. “Chromosomes” plots (Supplementary Information, Supplementary Figure S5 and Note, pages 3-4), which at least suggests a modifier or covariate could act as an effect “modifier” for dynamically changing the statistical relationship between the frequency distributions of reads and a particular percentile for threshold filtering.
Regarding dependent claims 20 and 21, Zheng et al. further shows upstream and downstream processing engines in a bioinformatics pipeline workflow for profiling RNAs from thousands of single cells using sequence read data wherein the read fragments contain barcodes and unique molecular identifiers (Figure 1(f)).
Regarding dependent claims 22-24, Zheng et al. further shows a bioinformatics pipeline workflow that receives data from a next-generation sequencer (Figure 1(a), (e), and (f)) which at least suggests that the data store and computing device are part an integrated apparatus wherein the data store is a different device than the computing device and both devices are part of a distributed network.
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 threshold filtering using a distribution percentile (i.e., a quantile-based model), as shown by Romanov 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 Romanov et al., because Romanov et al. shows methods for filtering cells based on a quality label (upper quartile) and a quality score above the 90th percentile, and a frequency distribution plot of sequence reads, suggesting the quantile model could be modified to be dynamic. This modification would have had a reasonable expectation of success given that both Zheng et al. and Romanov et al. disclose methods for processing sequence read data using barcodes and unique molecular identifiers to filter for particular cell-associated barcodes and/or unique molecular identifiers to identify and select read data for further analysis.
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.
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Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 of copending Application No. 18/090,814 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims 1-24 are directed to a data analysis process for identifying sequence read fragments with no biological meaning using threshold values for filtering read fragments based on an associated barcode and a unique identifier sequence, and reference claims 1, 2, 5, 7, 9-12, 15, 17, 19-22, 25, 27, and 29-32 are directed to a data analysis process for identifying barcodes that are associated with an actual molecule (i.e., biological meaning) using threshold values for filtering the barcodes.
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.
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/S.W.B./Examiner, Art Unit 1687
/Joseph Woitach/Primary Examiner, Art Unit 1687
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