DETAILED ACTION
The Applicant’s filing, received 13 April 2026, 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 13 April 2026 has been entered.
Status of the Claims
Claims 16-23 are pending.
Claims 16-23 are rejected.
Claim 20 is objected to.
Priority
This application is a 371 of PCT/EP2019/056354, filed 13 March 2019, which claims benefit of 62/642,877, filed 14 March 2018.
Claim Objections
Claim 20 is objected to because of the following informalities: The claim sets forth a plurality of elements or steps that are not separated by a line indentation (37 C.F.R. 1.75(i)) (see MPEP 608.01(i)).
Appropriate correction is required.
Claim Interpretation
The claim interpretation under 35 U.S.C. 112(f) in the Office action mailed 22 August 2024 has been withdrawn in view of the amendment received 13 April 2026.
The claim interpretation regarding claim 10 in the Office action mailed 22 August 2024 has been withdrawn in view of the amendment received 13 April 2026.
Claims 1-15 have been cancelled, and the newly provided claims do not provide limitations requiring analysis under 112f.
Claim Rejections - 35 USC § 112
The amendment received 13 April 2026 has been fully considered, however after further consideration, new grounds of rejection are raised under 35 U.S.C. 112(b) in view of the amendment.
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 16-23 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 16 recites the limitation "the plurality of gene sequences" in lines 9-10. There is insufficient antecedent basis for this limitation in the claim.
Claims 17-19 are indefinite for depending from claim 16 and for failing to remedy the indefiniteness of claim 16.
Claim 20 recites the limitation "the plurality of gene sequences" in line 15. There is insufficient antecedent basis for this limitation in the claim.
Claims 21-23 are indefinite for depending from claim 20 and for failing to remedy the indefiniteness of claim 20.
Claim Rejections - 35 USC § 101
The rejection of claims 1, 3, 4, 7-10, and 12-15 under 35 U.S.C. 101 in the Office action mailed 22 August 2024 has been withdrawn in view of the amendment received 13 April 2026.
The amendment received 13 April 2026 has been fully considered, however after further consideration, new grounds of rejection are raised under 35 U.S.C. 101 in view of the amendment.
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 16-23 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 16-19 are directed to a method for characterizing gene transcript expression levels (i.e., a process); and claims 20-23 are directed to a system for characterizing gene transcript expression levels (i.e., a machine or 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 16 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
extracting a plurality of distinct features from the plurality of gene transcripts (i.e., mental processes),
the plurality of distinct features resulting from varying splicing of genes from which the plurality of gene transcripts are transcribed, wherein the plurality of distinct features comprise one or more of a unique exon, a unique exon junction, a unique intron, a unique transcription start location, and/or a unique transcription stop location, and wherein a unique feature is unique to a subset of the plurality of gene sequences;
associating, in the distinct feature database, at least some of the extracted plurality of distinct features with annotation information identifying at least one of (i.e., mental processes)
a gene from which a respective distinct feature was extracted, a transcript from which the respective distinct feature was extracted, a genomic location of the respective distinct feature or associated transcript, an organism from which the respective distinct feature was extracted, and alternative splicing of the gene from which the respective distinct feature was extracted;
aligning the plurality of RNA sequencing reads to one or more of the extracted one or more distinct features stored in the distinct feature database (i.e., mental processes);
identifying, based on the aligning showing matching between an RNA sequencing reads and an extracted one or more distinct features stored in the distinct feature database, a gene transcript from which a respective RNA sequencing read was generated (i.e., mental processes);
obtaining, from the distinct feature database based on the identifying, annotation information associated with each matched distinct feature matching a respective one or more of the plurality of RNA sequencing reads (i.e., mental processes); and
compiling a summary of gene transcript expression levels in the obtained biological sample based on the identified gene transcripts (i.e., mental processes),
wherein the summary comprises the obtained annotation information from the distinct feature database associated with the identified gene transcripts and/or identified genes.
Independent claim 20 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
a plurality of gene transcripts comprising an entire transcriptome of an organism (i.e., mental processes);
a distinct feature database configured to store an extracted plurality of distinct features, and further configured to store annotation information associated with the extracted plurality of distinct features (i.e., mental processes);
extract a plurality of distinct features from the plurality of gene transcripts (i.e., mental processes),
the plurality of distinct features resulting from varying splicing of genes from which the plurality of gene transcripts are transcribed, wherein the plurality of distinct features comprise one or more of a unique exon, a unique exon junction, a unique intron, a unique transcription start location, and/or a unique transcription stop location, and wherein a unique feature is unique to a subset of the plurality of gene sequences;
associate, in the distinct feature database, at least some of the extracted plurality of distinct features with annotation information identifying at least one of (i.e., mental processes)
a gene from which a respective distinct feature was extracted, a transcript from which the respective distinct feature was extracted, a genomic location of the respective distinct feature or associated transcript, an organism from which the respective distinct feature was extracted, and alternative splicing of the gene from which the respective distinct feature was extracted;
align the plurality of RNA sequencing reads to one or more of the extracted one or more distinct features stored in the distinct feature database (i.e., mental processes);
identify, based on the aligning showing matching between an RNA sequencing reads and an extracted one or more distinct features stored in the distinct feature database, a gene transcript from which a respective RNA sequencing read was generated (i.e., mental processes);
obtain, from the unique feature database based on the identifying, annotation information associated with each matched distinct feature matching a respective one or more of the plurality of RNA sequencing reads (i.e., mental processes); and
compile a summary of gene transcript expression levels in the obtained biological sample based on the identified gene transcripts, wherein the summary comprises the obtained annotation information from the unique feature database associated with the identified gene transcripts and/or identified genes (i.e., mental processes).
Dependent claims 17-19 and 21-23 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claim 17 further recites:
identifying a gene transcript from which a respective RNA sequencing read was generated comprises a probability that the identified gene transcript is the transcript from which the respective RNA sequencing read was generated (i.e., mental processes and mathematical concepts).
Dependent claim 18 further recites:
a respective RNA sequencing read matches an extracted unique feature from two different gene transcripts (i.e., mental processes), and
said identifying step comprises identifying two or more gene transcripts from which the respective RNA sequencing read was generated or might have been generated (i.e., mental processes).
Dependent claim 19 further recites:
compiling a summary of gene transcript expression levels in the obtained biological sample based on the identified gene transcripts comprises summarizing the gene transcript expression levels as fragments per kilobase of transcript per million mapped reads values (i.e., mental processes).
Dependent claim 21 further recites:
identifying a gene transcript from which a respective RNA sequencing read was generated comprises a probability that the identified gene transcript is the transcript from which the respective RNA sequencing read was generated (i.e., mental processes and mathematical concepts).
Dependent claim 22 further recites:
a respective RNA sequencing read matches an extracted unique feature from two different gene transcripts (i.e., mental processes), and
said identifying step comprises identifying two or more gene transcripts from which the respective RNA sequencing read was generated or might have been generated (i.e., mental processes).
Dependent claim 23 further recites:
compiling a summary of gene transcript expression levels in the obtained biological sample based on the identified gene transcripts comprises summarizing the gene transcript expression levels as fragments per kilobase of transcript per million mapped reads values (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., extracting a plurality of distinct features from the plurality of gene transcripts), 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., identifying a gene transcript from which a respective RNA sequencing read was generated comprises a probability that the identified gene transcript is the transcript from which the respective RNA sequencing read was generated) are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Therefore, claims 16-23 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.
Dependent claims 17-19 and 21-23 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 16 include:
obtaining a plurality of gene transcripts comprising an entire transcriptome of an organism (i.e., obtaining data);
storing the extracted plurality of distinct features in a distinct feature database (i.e., storing data);
obtaining a biological sample for ribonucleic acid extraction and analysis;
extracting ribonucleic acid molecules from the biological sample for sequencing; and
sequencing, using a sequencing platform, the extracted ribonucleic acid molecules to generate a plurality of RNA sequencing reads representing an entire transcriptome of the biological sample.
The additional elements in independent claim 20 include:
a sequencing platform configured to generate, from extracted ribonucleic acid molecules, a plurality of RNA sequencing reads representing an entire transcriptome of a biological sample;
a processor;
store the extracted plurality of distinct features in the distinct feature database (i.e., store data); and
receive a plurality of RNA sequencing reads from the sequencing platform, the plurality of RNA sequencing reads obtained from extracted ribonucleic acid molecules and representing an entire transcriptome of a biological sample.
The additional element of a processor (claim 20); invokes a computer and/or computer-related components merely as a tool for use in the claimed process, and therefore is not an improvement to computer functionality itself, or an improvement to any other technology or technical field, and thus, does not integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(1)).
The additional element of obtaining a plurality of gene transcripts comprising an entire transcriptome of an organism (i.e., obtaining data) (claim 16); is 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)).
The additional elements of storing the extracted plurality of distinct features in a distinct feature database (i.e., storing data) (claim 16); and store the extracted plurality of distinct features in the distinct feature database (i.e., store data) (claim 20); are merely a pre-solution and/or a post-solution activity of saving 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)).
The additional elements of obtaining a biological sample for ribonucleic acid extraction and analysis (claim 16); extracting ribonucleic acid molecules from the biological sample for sequencing (claim 16); sequencing, using a sequencing platform, the extracted ribonucleic acid molecules to generate a plurality of RNA sequencing reads representing an entire transcriptome of the biological sample (claim 16); a sequencing platform configured to generate, from extracted ribonucleic acid molecules, a plurality of RNA sequencing reads representing an entire transcriptome of a biological sample (claim 20); and receive a plurality of RNA sequencing reads from the sequencing platform, the plurality of RNA sequencing reads obtained from extracted ribonucleic acid molecules and representing an entire transcriptome of a biological sample (claim 20); are pre-solution activities that are part of the gathering of data for use in the claimed process – nominal or tangential additions to the claims that do not meaningfully limit the claims, and therefore do 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 16-23 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 16-23 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 17-19 and 21-23 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 16 and 20 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 processor (claim 20); obtaining data (claim 16); and storing/store data (claims 16 and 20); 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).
The additional elements of obtaining a biological sample for ribonucleic acid extraction and analysis (claim 16); extracting ribonucleic acid molecules from the biological sample for sequencing (claim 16); sequencing, using a sequencing platform, the extracted ribonucleic acid molecules to generate a plurality of RNA sequencing reads representing an entire transcriptome of the biological sample (claim 16); a sequencing platform configured to generate, from extracted ribonucleic acid molecules, a plurality of RNA sequencing reads representing an entire transcriptome of a biological sample (claim 20); and receive a plurality of RNA sequencing reads from the sequencing platform, the plurality of RNA sequencing reads obtained from extracted ribonucleic acid molecules and representing an entire transcriptome of a biological sample (claim 20); are conventional. Evidence of conventionality is shown by:
Mutz et al. (“Transcriptome analysis using next-generation sequencing.” Current Opinion in Biotechnology, 2013, vol. 24, pp. 22-30, as cited in the Office action mailed 28 February 2024);
Jiang et al. (“Whole transcriptome analysis with sequencing: methods, challenges and potential solutions.” Cellular and Molecular Life Sciences, 2015, vol. 72, pp. 3425-3439); and
Ali et al. (“Current nucleic acid extraction methods and their implications to point-of-care diagnostics.” BioMed Research International, 2017, Article ID 930656, pp. 1-13).
Mutz et al. reviews transcriptome analysis using next-generation sequencing (Title; and Abstract) and shows that next-generation sequencing (NGS) technologies have been successfully applied to gene expression profiling and that NGS enables the absolute quantification of transcripts which helps to detect changes of gene expression levels under different biological conditions or between different cell types or tissues (page 26, column 2, para. 6).
Jiang et al. reviews transcriptome analysis methods and technologies that have been used to conduct whole transcriptome shotgun sequencing or whole transcriptome tag/target sequencing analyses (Abstract; and throughout).
Ali et al. reviews each of the most common nucleic acid extraction methods, overviewing their advantages and disadvantages, as well as their potential for integration into point-of-care diagnostics (Abstract; and throughout).
Therefore, when taken alone, all additional elements in claims 16-23 do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as a combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 16-23 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]
Response to Arguments
The Applicant’s arguments/remarks received 13 April 2026 have been fully considered, but are not persuasive.
The Applicant provides a brief summary of Step 2A, Prong One of the eligibility analysis on page 7 (para. 1) of the Remarks, and provides a passage from the Office action mailed 22 August 2024 regarding now canceled claim 1 (Remarks, para. 2) and states (para. 3) that rather than being directed to a mental process, the claims are directed to a specific system and method for characterizing gene transcript expression levels using a very specific process and/or system, and further states that the claims comprise, for example, a process that cannot be completed in the human mind alone, and that, for example, the human mind cannot store the extracted plurality of distinct features in a distinct feature database or associate, in the distinct feature database, at least some of the extracted plurality of distinct features with annotation information, or extract ribonucleic acid molecules from the biological sample for sequencing, or sequence, using a sequencing platform, the extracted ribonucleic acid molecules to generate a plurality of RNA sequencing reads representing an entire transcriptome of the biological sample, or align the plurality of RNA sequencing reads to one or more of the extracted one or more distinct features stored in the distinct feature database. The Applicant further states (Remarks, page 8, para. 2) that most or all of these steps are much more than simple pre- or post-solution activity, or generic data gathering activity, and that, e.g., the steps of associating, in the distinct feature database, at least some of the extracted plurality of distinct features with annotation information and sequencing, using a sequencing platform, the extracted ribonucleic acid molecules to generate a plurality of RNA sequencing reads representing an entire transcriptome of the biological sample, and aligning the plurality of RNA sequencing reads to one or more of the extracted one or more distinct features stored in the distinct feature database are fundamental aspects of the claimed method and system, not simply pre- or post-solution activity, or generic data gathering activity.
These arguments are not persuasive, because first, regarding the limitations mentioned in the foregoing argument, the above rejection identifies the limitations reciting “store the extracted plurality of distinct features in the distinct feature database;” “extracting ribonucleic acid molecules from the biological sample for sequencing;” and “sequencing, using a sequencing platform, the extracted ribonucleic acid molecules to generate a plurality of RNA sequencing reads representing an entire transcriptome of the biological sample;” as additional elements at Step 2A Prong Two (i.e., not judicial exceptions). Second, regarding the limitations mentioned in the foregoing argument, the above rejection identifies the limitations reciting “associating, in the distinct feature database, at least some of the extracted plurality of distinct features with annotation information;” and “aligning the plurality of RNA sequencing reads to one or more of the extracted one or more distinct features stored in the distinct feature database;” as mental processes at Step 2A Prong One (i.e., judicial exceptions), because they set forth and/or describe data processing steps that can practically be performed in the human mind with or without pen and paper. Third, as noted and discussed at MPEP 2106.05(g), an example of pre-solution activity is a step of gathering data for use in a claimed process.
The Applicant provides a brief summary of Step 2A, Prong Two of the eligibility analysis on page 8 (para. 4) of the Remarks, and states (para. 5) that the claims are not directed to a judicial exception, and that the claims do indeed incorporate any judicial exception into a practical application. The Applicant further states that even assuming, arguendo, that the claims are directed to an abstract idea, the elements of the independent claims, individually and in combination, integrate the exception into a practical application, and further states (para. 6) that the independent claims are directed to the practical application of characterizing gene transcript expression levels, and as such, the presently claimed invention focuses on a specific improvement to the technical field of analyzing gene transcripts. The Applicant further states (para. 7, and page 9, para. 1) that the claims also comprise a practical application because the invention applies and uses the alleged abstract idea in a particular technological environment, and that the claims recite a combination of elements encompassing a very specific physical system for characterizing gene transcript expression levels, comprising at least a database of unique features extracted from each of a plurality of gene transcripts, as well as a plurality of sequences generated from gene transcripts, and compiled information about gene transcript expression levels based on said identified gene transcripts, and accordingly, (para. 2) the claims do indeed incorporate any judicial exception into a practical application.
These arguments are not persuasive, because first, with regard to the Applicant’s argument that the elements of the independent claims, individually and in combination, integrate the exception into a practical application, it is noted that when all limitations in claims 16-23 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, because the claims do not recite any additional elements that apply, rely on, or use the judicial exception(s) in a manner that imposes a meaningful limit on the judicial exception(s). Second, with regard to the Applicant’s argument that the independent claims are directed to the practical application of characterizing gene transcript expression levels, and as such, the presently claimed invention focuses on a specific improvement to the technical field of analyzing gene transcripts, it is noted that characterizing gene transcript expression levels (i.e., analyzing data) comprises the abstract idea of analyzing genomic data, and because a judicial exception alone is not eligible subject matter, integration into a practical application is evaluated by: (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception(s); and (2) evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application, using one or more of the considerations introduced in subsection I at 2106.04(d) of the MPEP, and discussed in more detail in MPEP §§ 2106.04(d)(1), 2106.04(d)(2), 2106.05(a) through (c) and 2106.05(e) through (h). Third, with regard to the Applicant’s argument that the claims also comprise a practical application because the invention applies and uses the alleged abstract idea in a particular technological environment, and that the claims recite a combination of elements encompassing a very specific physical system for characterizing gene transcript expression levels, it is important to note, the judicial exception (i.e., characterizing gene transcript expression levels) alone cannot provide the improvement. The improvement can be provided by one or more additional elements, and as noted and discussed in the above rejection and also in the foregoing responses to arguments, the claims do not recite any additional elements that apply, rely on, or use the judicial exception(s) in a manner that imposes a meaningful limit on the judicial exception(s), and therefore the instant claims are directed to the abstract idea(s), as noted in the above rejection.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3, 4, 7-10, and 12-15 under 35 U.S.C. 103 as being unpatentable over Cloonan et al. in view of Vickers et al. in view of Li et al. in the Office action mailed 22 August 2024 has been withdrawn in view of these claims having been cancelled in the amendment received 13 April 2026.
The Applicant’s amendment received 13 April 2026 has been fully considered, however after further consideration, new grounds of rejection are raised under 35 U.S.C 103 in view of the amendment.
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 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 16-23 are rejected under 35 U.S.C. 103 as being unpatentable over Cloonan et al. (Nature Methods, 2008, Vol. 5, No. 7, pp. 613-619; and Supplementary Figures and Text, pp. 1-89, cited as two separate documents in the Information Disclosure Statement (IDS), received 09 September 2020) in view of Vickers et al. (PLoS ONE, 2014, Vol. 9(10), pp. 1-12, as cited in the Office action mailed 08 May 2023) in view of Li et al. (EMBO Reports, 2016, Vol. 17, No. 2, pp. 178-187, as cited in the Office action mailed 08 May 2023) in view of Trapnell et al. (“Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks.” Nature Protocols, 2012, vol. 7(3), pp. 562-578, newly cited).
Independent claims 16 and 20 are broadly directed to a method and system for characterizing gene transcript expression levels from ribonucleic acid molecules, comprising extracting distinct features from gene transcripts, and associating the extracted distinct features with annotation information stored in a database in order to identify characteristics associated with the extracted distinct feature, e.g., the gene and/or the transcript from which the distinct feature was extracted from; and aligning RNA sequence reads generated from a biological sample to at least one of the extracted distinct features and identifying, based on the alignment, a gene transcript from which the RNA sequence read was generated, and compiling a summary of gene expression levels, wherein the summary comprises annotation information from the database that is associated with the identified gene and/or transcript.
Dependent claims 17-19 and 21-23 further define the method of characterizing, e.g., identifying a gene transcript based on a probability; identifying at least two gene transcripts from which a respective RNA sequence read was generated or might have been generated; and summarizing the gene expression levels as fragments per kilobase of transcript per million mapped reads values.
Cloonan et al. is directed to a massive-scale RNA sequencing protocol called SQRL (i.e., short quantitative random RNA libraries) to survey the complexity, dynamics and sequence content of transcriptomes in order to capture the genomic landscape of expression, state-specific expression, single-nucleotide polymorphisms (SNPs), the transcriptional activity of repeat elements, and both known and new alternative splicing events.
Vickers et al. is directed to a strategy for analyzing the human transcriptome and identifying unique repeated sequences of 16 or more nucleotides in length within genes.
Li et al. is directed to the use of single-cell RNA-seq to establish a transcriptional dataset and a comprehensive transcriptome database.
Trapnell et al. is directed to software tools for gene discovery and comprehensive expression analysis of high-throughput mRNA sequencing (RNA-seq) data that allow biologists to identify new genes and new splice variants of known ones, as well as compare gene and transcript expression under two or more conditions.
Regarding independent claims 16 and 20, Cloonan et al. shows a system and method for characterizing transcription in exons of known genes (page 615, column 2, para. 2); a database for storing unique exon-junction sequences in contrast to complete transcripts (page 614, column 1, para. 1); comparison of ‘short quantitative random RNA libraries’ (SQRL) tags with diagnostic sequence annotations (page 615, column 1, para. 1); quantifying transcripts (page 615, column 1, para. 1); combining all tag maps with existing genome and transcriptome annotations available in the UCSC Genome Browser (page 614, column 2, para. 2); using a probability algorithm to assign (i.e., identify) SQRL gene expression tags that are multiple mappers (MuMs) of different gene transcripts to their most likely source (Supplementary Figure 2); single-mapping alignments to identify junctions excluded from original junction set because their sequence occurred in multiple genes (page 615, column 2, para. 3); and compiling a summary of all transcriptional data (page 616, column 2, para. 3; and Table 1).
Regarding independent claims 16 and 20, Cloonan et al. does not explicitly show: extracting distinct features from a plurality of gene transcripts; obtaining a biological sample for ribonucleic acid extraction and analysis; or compiling a summary of gene transcript expression levels in the obtained biological sample based on the identified gene transcripts, wherein the summary comprises the obtained annotation information from the distinct feature database associated with the identified gene transcripts and/or identified genes.
Regarding independent claims 16 and 20, Vickers et al. shows that a significant fraction of the transcriptome contains repeated sequences present in only on target RNA (page 2, column 1, para. 3) and a software program for extracting these unique sequences from primary and processed transcripts and determining their locations in the genome (page 2, column 1, Material and Methods: para. 1) in order to target antisense oligonucleotides (ASOs) to the unique sequences to generate increased specificity of therapeutics (page 2, column 1, para. 3).
Regarding independent claims 16 and 20, Li et al. shows a workflow for obtaining and analyzing single-cell RNA-seq data from human pancreatic islets (Figure 1(A), page 179 (bottom) and page 180); and obtaining human islet cells for culturing (page 184, col. 1, para. 4) and for RNA-seq sample and sequencing library preparation (page 184, col. 2, para. 2).
Regarding independent claims 16 and 20, Trapnell et al. shows merging transfrags (i.e., transcript fragments) with annotated reference transcripts into a merged file assembly to produce a single annotation file for use in downstream differential analyses (page 5, para. 4; and Figure 3); Trapnell et al. further shows that reads are independently mapped to a reference genome, and then the mapped reads are assembled into a file of transfrags and subsequently merged with the reference transcriptome annotation resulting in a unified annotation that can be used for further analysis, i.e., quantification, which produces expression data in a set of indexed tabular files which can be visualized to facilitate exploration of genes identified as differentially expressed, spliced, or transcriptionally regulated genes (page 26, Figure 2). Trapnell et al. further shows that whenever possible, a reference annotation should be included in a merged transcriptome assembly file (page 17, para. 2 and Table 4). Trapnell et al. further shows an example of a bioinformatics analytical procedure (pages 12-16, PROCEDURE: Steps 1-18) beginning at the mapping step (i.e., Step 1) and at Step 15 produces a number of output files and statistics, e.g., a simple table for each assembly that lists how many transcripts in each assembly are complete matches to known transcripts, how many are partial matches, and so on.
Regarding dependent claims 17, 18, 21, and 22, Cloonan et al. shows potential transcript variants for genes, with genes that have evidence for more than one transcript differentiated from genes that have evidence for expression of only one transcript (Figure 4); and genome mappings are sorted into single-mappers (SiMs) or multi-mappers (MuMs) (Supplementary Figure 1) and MuMs are assigned to their most likely source probabilistically (Supplementary Figure 2).
Regarding dependent claims 19 and 23, Cloonan et al. does not explicitly show summarizing the gene transcript expression levels as fragments per kilobase of transcript per million mapped reads values.
Regarding dependent claims 19 and 23, Trapnell et al. further shows examples of exploring expression data and creating publication-ready plots of differentially expressed and regulated genes based on fragments per kilobase of transcript per million fragments mapped (FPKM) (e.g., Figure 5 on page 29).
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 Cloonan et al. by incorporating methods for extracting distinct features from transcripts, as shown by Vickers et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Cloonan et al. with the methods of Vickers et al., because Vickers et al. shows a method for the extraction of 16-mer sequences from processed transcripts that are often found as repeats but are unique to a particular gene. This modification would have had a reasonable expectation of success given that Cloonan et al. discloses methods for calculating locus activity by counting the numbers of tags mapping to exons (i.e., coding regions) of genes and identifying potential transcript variants for the genes based on evidence of at least 2 tags, and Vickers et al. discloses methods for identifying and extracting repeat sequences from transcripts that are unique to single genes in the human transcriptome by evaluating repeated sequences in both exons and introns.
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 Cloonan et al. by incorporating methods for obtaining and processing a biological sample for ribonucleic acid extraction and analysis, as shown by Li et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Cloonan et al. with the methods of Li et al., because Li et al. shows obtaining a biological sample and performing RNA-seq to establish a comprehensive transcriptome database for specific cell types for downstream data analyses. This modification would have had a reasonable expectation of success given that both Cloonan et al. and Li et al. disclose methods for profiling the human transcriptome.
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 Cloonan et al. by incorporating methods for using software tools specifically developed for differential gene and transcript expression analyses for profiling transcriptomes, as shown by Trapnell et al. and discussed above. One of ordinary skill in the art would have been motivated to combine the methods of Cloonan et al. with the methods of Trapnell et al., because Trapnell et al. shows a software-based protocol that begins with raw sequencing reads and produces a transcriptome assembly, lists of differentially expressed and regulated genes and transcripts, and publication-quality visualizations and analysis results. This modification would have had a reasonable expectation of success given that both Cloonan et al. and Trapnell et al. disclose methods for profiling the human transcriptome.
Response to Arguments
The Applicant’s arguments received 13 April 2026 have been fully considered, but are not persuasive.
The Applicant states on page 9 (para. 4) of the Remarks that regarding new claims 16-23, Cloonan in view of Vickers and Li fails to suggest or render obvious a method or system for characterizing gene transcript expression levels from ribonucleic acid molecules in a biological sample from an organism, comprising the limitations recited by independent claim 16. The Applicant further states on page 10 (para. 2) that, e.g., the Patent Office asserts that Cloonan discloses compiling a summary, specifically, that Cloonan teaches “compiling a summary of all transcriptional data,” however, Cloonan (alone or in combination with Vickers and Li) fails to disclose or suggest “compiling a summary of gene transcript expression levels in a biological sample based on the identified gene transcripts, wherein the summary comprises the obtained annotation information from the distinct feature database associated with the identified gene transcripts and/or identified genes.” The Applicant further states (para. 3) that in addition, Cloonan in view of Vickers and Li fails to suggest or render obvious several other elements of the claimed method and system.
These arguments are not persuasive, because the new grounds of rejection in view of the amendment relies on a new combination of references to show the limitation reciting “compiling a summary of gene transcript expression levels in a biological sample based on the identified gene transcripts, wherein the summary comprises the obtained annotation information from the distinct feature database associated with the identified gene transcripts and/or identified genes,” as noted in the above rejection.
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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