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 .
Claims Status
Claims 1-15 are pending.
Claims 1-15 are examined.
Priority
The instant application is a national stage application of PCT/EP2021/050536, filed 01/13/2021, which claims priority to provisional US Application No. 62/963250, filed 01/20/2020. Therefore, the Effective Filing Date (EFD) assigned to each of the claims 1-15 is the provisional filing date of Application No. 62/963250, filed 01/20/2020.
Information Disclosure Statement
The Information Disclosure Statements filed 07/20/2022, and 11/21/2025 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
It is noted that certain references lack appropriate page numbers as is required under 37 CFR 1.97. The Examiner has annotated the references herein. Applicant is kindly reminded to provide proper citations in compliance with 37 CFR 1.97 in all future submission to the office.
Drawings
The drawings filed 07/20/2022 are accepted.
Specification
The disclosure is objected to because of the following informalities:
In paragraph [0031], line 2, “sample,.” should read “sample
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to claim 1, the claim recites the limitations of “validate at least some of the plurality of identified variants”, “a report comprising the identified variants”, “for each identified variant”, etc. The claim is indefinite because there is no antecedent basis for the identified variants or each identified variant, and thus it is unclear what variants the claim limitation is referring to.
With further respect to claim 1, the claim recites the limitation of “validate at least some”. The claim is indefinite because the term “some” is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
With further respect to claim 1, the claim recites the limitation of “compare the obtained gene expression data”. The claim is indefinite because there is no antecedent basis for “the obtained gene expression data” and thus it is unclear what expression data is being compared in this step.
With further respect to claim 1, the claim recites the limitation of “compare the obtained gene expression data to the obtained expression comparison data”. The claim is indefinite because there is no antecedent basis for “the obtained expression comparison data”. The claims are directed to a system comprising gene expression comparison data, however, there is no active step of obtaining, thus it is unclear what “the obtained expression comparison data” is and what gene expression data is being compared.
With respect to claim 4, the claim recites the limitation of “validating at least some”. The claim is indefinite because the term “some” is a relative term which renders the claim indefinite. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
With respect to claim 11, the claim recites the limitation of “The method of claim 4, wherein the single cell analysis system comprises a machine learning algorithm”. The claim is indefinite because it should be directed to a method, but the limitations further limit the elements that comprise the system. Thus, it is unclear if the claim is directed to a method step or to a system structure.
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 1-15 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims recite a system and methods.
With respect to step (2A)(1): The claims are directed to abstract ideas of mental processes and mathematical concepts.
“Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection” (MPEP 2106.04). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claim 1:
gene expression comparison data, comprising one or more gene expression profiles
(i) validate at least some of the plurality of identified variants using the variant validation data, comprising for each identified variant: comparing the identified variant to the validation data; and assigning a validated classification status to the variant if the variant corresponds to the validation data
(ii) compare the obtained gene expression data to the obtained expression comparison data
(iii) generate, based on the comparison and using a projection function, a final gene expression profile for the single cell sample
provide a report comprising the identified variants assigned with a validated classification status and the generated final gene expression profile for the single cell sample
Mental processes recited in claim 4:
identifying, from DNA sequencing data, a plurality of variants in the DNA sequencing data
validating at least some of the plurality of identified variants using the obtained variant validation data, comprising for each identified variant: (i) comparing the identified variant to the validation data; and (ii) assigning a validated classification status to the variant if the variant corresponds to the validation data
compiling at least those identified variants assigned with a validated classification status to generate a report comprising characterized DNA sequence for the single cell sample, and providing the report
Mental processes recited in claim 12:
comparing the obtained gene expression data to the obtained expression comparison data
generating, based on the comparison and using a projection function, a final gene expression profile for the single cell sample
generating and providing a report comprising the generated gene expression profile for the single cell sample
Dependent claims 5, 6, 10, and 11 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claims 1, 4, and 12, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 5: “assigning an unvalidated classification status to the variant if the variant does not correspond to the validation data, and wherein the report comprises one or more unvalidated variants”
Claim 6: “wherein the classification status comprises a validation confidence level”
Claim 10: “wherein the step of identifying a plurality of variants in the DNA sequencing data comprises guided variant calling using the variant validation data”
Claim 11: “wherein the single cell analysis system comprises a machine learning algorithm configured to validate variants identified in the DNA sequencing data, wherein the machine learning algorithm is trained using the variant validation data”
The abstract ideas in the claims are evaluated under Broadest Reasonable Interpretation (BRI) and determined herein to each cover mental processes and mathematic concepts because the claims recite no more than identifying elements in sequence data and comparing sequence data, which comprise mental processes.
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claim 1 recites the following additional elements that are not abstract ideas:
variant validation data comprising a plurality of variants from DNA sequencing
single cell DNA sequencing data
single cell RNA sequencing data
a processor
a user interface
Claim 4 recites the following additional elements that are not abstract ideas:
using a single cell analysis system
obtaining variant validation data, the variant validation data comprising a plurality of variants from DNA sequencing
obtaining DNA sequencing for the single cell sample
Claim 12 recites the following additional elements that are not abstract ideas:
using a single cell analysis system
obtaining gene expression data for the single cell sample
The steps of obtaining sequence, validation, and gene expression data generate the data on which the judicial exceptions are performed. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)). The element of a single cell analysis system, a processor, and user interface are directed to generic computer elements because the claims do not recite specific step of how these elements implement the steps. Hence, these are interpreted as mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc. ... are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (see MPEP 2106.05(f)).
Dependent claims 2, 3, 7, 8, 9, and 13-15 are directed to steps of data gathering or further limit the data gathering steps and thus are directed to elements of data gathering.
None of these dependent claims recite additional elements, alone or in combination, which would integrate a judicial exception into a practical application.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP at 2106.05(d)(I), determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claim 1: The additional elements of a processor, user interface, variant validation data comprising a plurality of variants from DNA sequencing data, single cell DNA sequencing data, and single cell RNA sequencing data do not rise to the level of significantly more than the judicial exception. The prior art to Liang et al. (“Single-Cell Sequencing Technologies: Current and Future”, published 2014) discloses numerous experiments generating single cell RNA and DNA sequence data (Table 1). As recited in the MPEP at 2106.05(d).II, with reference to Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, and University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), detecting variants in DNA sequence information is a well-understood and routine technique. Furthermore, with respect to the processor and user interface, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 2: The additional elements of pooled DNA sequencing data obtained from each of a plurality of single cells from the same sample, verified variants obtained from bulk sequencing data, and/or variant data obtained from a public or private database do not rise to the level of significantly more than the judicial exception. As recited in the MPEP at 2106.05(d).II, with reference to Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, and University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), detecting variants in bulk DNA sequence information is a well-understood and routine technique. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 3: The additional elements of pooled gene expression obtained from each of a plurality of single cells from the same sample, a gene expression profile obtained from bulk RNA sequencing data, and/or a plurality of gene expression profiles obtained from a public or private database do not rise to the level of significantly more than the judicial exception. As recited in the MPEP at 2106.05(d).II, with reference to University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), amplifying and sequencing bulk nucleic acid sequences is a well-understood and routine activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 4: The additional elements of a single cell analysis system, obtaining variant validation data, the variant validation data comprising a plurality of variants from DNA sequencing data, and obtaining DNA sequencing data for the single cell sample do not rise to the level of significantly more than the judicial exception. The prior art to Liang et al. discloses numerous experiments generating single cell RNA and DNA sequence data (Table 1). As recited in the MPEP at 2106.05(d).II, with reference to Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, and University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), detecting variants in DNA sequence information is a well-understood and routine technique. Furthermore, with respect to the system, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 7: The additional element of pooled DNA sequencing data obtained from each of a plurality of single cells from the same sample does not rise to the level of significantly more than the judicial exception. The prior art to Liang et al. discloses numerous experiments generating single cell RNA and DNA sequence data (Table 1). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 8: The additional element of verified variants obtained from bulk DNA sequencing data does not rise to the level of significantly more than the judicial exception. As recited in the MPEP at 2106.05(d).II with reference to Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, and University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), detecting variants in bulk DNA sequence information is a well-understood and routine technique. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 9: The additional element of variant data obtained from a public or private database does not rise to the level of significantly more than the judicial exception. As recited in the MPEP at 2106.05(d).II with reference to Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, storing and retrieving information in memory is a well-understood and routine technique. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 12: The additional elements of a single cell analysis system and obtaining gene expression data for the single cell sample do not rise to the level of significantly more than the judicial exception. The prior art to Liang et al. discloses numerous experiments generating single cell RNA and DNA sequence data (Table 1). Furthermore, with respect to the system, as exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 13: The additional element of pooled gene expression obtained from each of a plurality of single cells from the same sample does not rise to the level of significantly more than the judicial exception. The prior art to Liang et al. discloses numerous experiments generating single cell RNA and DNA sequence data (Table 1). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 14: The additional element of a gene expression profile obtained from bulk RNA sequencing data does not rise to the level of significantly more than the judicial exception. With reference to University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), amplifying and sequencing bulk nucleic acid sequences is a well-understood and routine activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 15: The additional element of a plurality of gene expression profiles obtained from a public or private database does not rise to the level of significantly more than the judicial exception. As recited in the MPEP at 2106.05(d).II with reference to Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, storing and retrieving information in memory is a well-understood and routine technique. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
In combination, the collection or generation of the data, acted upon by the judicial exception, fail to rise to the level of significantly more. The data gathering steps provide the data for the judicial exception. No non-routine step or element has clearly been identified.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 6, 9-15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Newman et al. (WO 2019/018684 A1, published 24 January 2019, IDS reference).
Regarding claim 1, Newman et al. teaches a single cell analysis system (paragraph [0026]) configured to generate a variant profile and a gene expression profile from a single cell sample, comprising:
variant validation data comprising a plurality of variants from DNA sequencing data (paragraph [0150];
gene expression comparison data, comprising one or more gene expression profiles (paragraph [0007]);
single cell DNA sequencing data, utilized to identify a plurality of variants (paragraph [0007]);
single cell RNA sequencing data, utilized to generate a gene expression profile for the single cell sample (paragraph [0007]);
a processor (paragraph [0026]) configured to:
validate at least some of the plurality of identified variants using the variant validation data, comprising for each identified variant: comparing the identified variant to the validation data; and assigning a validated classification status to the variant if the variant corresponds to the validation data (Figure 6, A; paragraph [0260]; paragraph [0055]);
compare the obtained gene expression data to the obtained expression comparison data (paragraphs [0039]; [0043]); and
generate, based on the comparison and using a projection function (paragraph [0043]), a final gene expression profile for the single cell sample (Figure 1, (4)); and
a user interface configured to provide reports of identified variants assigned with a validated classification status and the generated final gene expression profile for the single cell sample through the generation of signature gene matric (paragraphs [0179]; [0206]).
Regarding claim 2, the claim is directed to the variant validation data comprising pooled DNA sequencing data obtained from each of a plurality of single cells from the same sample, verified variants obtained from bulk DNA sequencing data, and/or variant data obtained from a public or private database. Newman et al. teaches the system of claim 1. Newman et al. also teaches variant validation data comprising CEL data files pooled with variant data obtained from a public database (paragraph [0150]). Furthermore, Newman et al. teaches the variant data was obtained using bulk sequencing (paragraph [0259]).
Regarding claim 3, the claim is directed to the gene expression comparison data comprising pooled gene expression obtained from each of a plurality of single cells from the same sample, a gene expression profile obtained from bulk RNA sequencing data, and/or a plurality of gene expression profiles obtained from a public or private database. Newman et al. teaches the system of claim 1. Newman et al. teaches the gene expression comparison data comprising gene expression profiles obtained through pooled gene expression data obtained from a plurality of single cells from the sample (paragraph [0007]).
Regarding claim 4, Newman et al. teaches a method for characterizing a DNA sequence of a single cell sample using a single cell analysis system (paragraph [0026]), comprising:
obtaining variant validation data, the variant validation data comprising a plurality of variants from DNA sequencing data (paragraph [0260];
obtaining DNA sequencing data for the single cell sample (paragraphs [0007]; [0120]);
identifying, from DNA sequencing data, a plurality of variants in the DNA sequencing data (paragraph [0260]);
validating at least some of the plurality of identified variants using the obtained variant validation data, comprising for each identified variant: (i) comparing the identified variant to the validation data; and (ii) assigning a validated classification status to the variant if the variant corresponds to the validation data (Figure 6, A; paragraph [0260]; paragraph [0055]); and
compiling at least those identified variants assigned with a validated classification status to generate a report comprising characterized DNA sequence for the single cell sample, and providing the report (Figure 6, B).
Regarding claim 6, the claim is directed to the classification status comprising a validation confidence level. Newman et al. teaches the method of claim 4. Newman et al. also teaches the classifying of variants comprising a validation statistical confidence level in the differential expression of the variants (paragraph [0254]).
Regarding claim 9, the claim is directed to the variant validation data comprising variant data obtained from a public or private database. Newman et al. teaches the method of claim 4. Newman et al. also teaches variant validation data comprising CEL data files pooled with variant data obtained from a public database (paragraph [0150]).
Regarding claim 10, the claim is directed to the step of identifying a plurality of variants in the DNA sequencing data comprising guided variant calling using the variant validation data. Newman et al. teaches the method of claim 4. Newman et al. teaches reference guided variant calling in a DNA sequence (paragraphs [0124]; [0260]).
Regarding claim 11, the claim is directed to the single cell analysis system comprising a machine learning algorithm configured to validate variants identified in the DNA sequencing data, wherein the machine learning algorithm is trained using the variant validation data. Newman et al. teaches the method of claim 4. Newman et al. also teaches deriving signature matrices using machine learning trained on variant validation data (paragraphs [0143]; [0154]; [0215]).
Regarding claim 12, Newman et al. teaches a method for generating a gene expression profile from a single cell sample using a single cell analysis system (paragraph [0026]), comprising:
obtaining gene expression comparison data comprising a gene expression profile (Figure 3, A, bulk expression profiles);
obtaining gene expression data for the single cell sample (Figure 3, A, scRNA-seq);
comparing the obtained gene expression data to the obtained expression comparison data (Figure 3, A);
generating, based on the comparison and using a projection function, a final gene expression profile for the single cell sample (paragraph [0037]; paragraph [0043]; Figure 3, A); and
generating and providing a report comprising the generated gene expression profile for the single cell sample (Figure 3, F and G).
Regarding claim 13, the claim is directed to the gene expression comparison data comprising pooled gene expression obtained from each of a plurality of single cells from the same sample. Newman et al. teaches the method of claim 12. Newman et al. also teaches the comparison data comprising pooled gene expression obtained from a plurality of single cells from a sample (paragraph [0043], (7f)).
Regarding claim 14, the claim is directed to the gene expression comparison data comprising a gene expression profile obtained from bulk RNA sequencing data. Newman et al. teaches the method of claim 12. Newman et al. teaches gene expression comparison data comprising bulk tissue RNA profiles (paragraph [0037]).
Regarding claim 15, the claim is directed to the gene expression comparison data comprising a plurality of gene expression profiles obtained from a public or private database. Newman et al. teaches . the method of claim 12. Newman et al. also teaches the gene expression comparison data comprising gene expression profiles obtained from a publicly available database (paragraph [0123]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 5, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Newman et al., as applied to claims 1-4, 6, 9-15 in the 102 rejection above.
Regarding claim 5, the claim is directed to assigning an unvalidated classification status to the variant if the variant does not correspond to the validation data, and wherein the report comprises one or more unvalidated variants. Newman et al. teaches the method of claim 4. Newman et al. teaches validating expressed genes between the bulk sequence set and the single cell set (Figure 18C)
Although Newman et al. does not explicitly teach the claim element of assigning an unvalidated classification status, 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 assigned an unvalidated status to variations not found within the validation data as Newman et al. teaches validating the genes present in the validation data.
Regarding claim 7, the claim is directed to the variant validation data comprising pooled DNA sequencing data obtained from each of a plurality of single cells from the same sample. Newman et al. teaches the method of claim 4. Newman et al. teaches variant validation data comprising pooled RNA sequencing data from a plurality of single cells from a sample (paragraph [0042], single cell validation data; Figure 19A, mean scRNA-Seq). Furthermore, Newman et al. teaches measuring cell genotypes using DNA sequencing (paragraph [0120]).
Although Newman et al. does not explicitly teach the claim element of the validation data comprising pooled DNA sequencing data, it would have been prima facie obvious toe one of ordinary skill in the art before the effective filing date of the claimed invention to have used pooled DNA sequences of single cells as validation data because Newman et al. teaches using single cell data as validation data, and teaches measuring cell genotypes using DNA sequencing, and thus it would be obvious to try using pooled single cell DNA sequences.
Regarding claim 8, the claim is directed to the variant validation data comprising verified variants obtained from bulk DNA sequencing data. Newman et al. teaches the method of claim 4. Newman et al. teaches the variant validation data was obtained using bulk sequencing (paragraph [0259]). Furthermore, Newman et al. teaches measuring cell genotypes using DNA sequencing (paragraph [0120]).
Although Newman et al. does not explicitly teach the claim element of bulk DNA sequencing, it would have been prima facie obvious toe one of ordinary skill in the art before the effective filing date of the claimed invention to have obtained the variants using bulk DNA sequencing as Newman et al. teaches bulk sequencing data and teaches measuring cell genotypes and features using DNA sequencing, and thus it would be obvious to try using bulk DNA sequencing.
Conclusion
No claims are allowed.
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/E.A.S./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686