DETAILED ACTION
Applicant's response, filed 08/11/2026, has been fully considered.
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 .
Priority
This application filed 01/17/2023 claims priority from Provisional Application 63299752, filed 01/14/2022. The claims are therefore examined as filed on 01/14/2022, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Election/Restrictions
Claims 11-13, 15-20, and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/11/2026.
Applicant’s election without traverse of claims 1-7, 10, and 29 in the reply filed on 08/11/2026 is acknowledged.
Claim Status
Claims 1-20, 22, and 29 are pending.
Claims 5-6 are objected to.
Claims 9, 11-13, 15-20, and 22 are withdrawn.
Claims 1-7, 10, and 29 are directed to the elected invention.
Claims 8, 21, 23-28, and 30-32 are cancelled.
Claims 1-7, 10, and 29 are examined.
Claims 1-7, 10, and 29 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 54-62). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 5-6 are objected to because of the following informalities:
Claim 5 should be formatted as it is in the specification [0009], and should be referred to as equation 1 instead of equation 2 to match the specification
Claim 6 should similarly be referred to as equation 2 instead of equation 3, as this is how it is referred to in the specification.
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.
Claim 6 is 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 6 is unclear as the terms of the equation in this claim are not defined. The Examiner recommends including definitions for the equation terms as they appear in [0009] of the specification (under equation 2).
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 1-7, 10, and 29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental processes and mathematical concepts, without significantly more.
The MPEP at MPEP 2106 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of matter?
(2A)(1) Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea?
(2A)(2) Do the claims recite additional elements that integrate the judicial exception into a practical application?
(2B) If the claims recite a judicial exception and do not integrate the judicial exception, do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?
With regard to step (1) (Are the claims directed to a process, machine, manufacture or composition of matter?): Yes. The claims are directed to one of the statutory classes. Claims 1-7 and 10 are directed to a process (a method), claim 29 are directed to a product (a system comprising a database and computer processors).
With regard to step (2A)(1) (Do the claims recite a judicially recognized exception?): Yes. The claims recite the abstract ideas of processing data using mental steps and mathematical concepts. Claims that recite nothing more than abstract ideas, natural phenomena, or laws of nature are not eligible for patent protection (see 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 (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include but are not limited to:
Computing a model for a plurality of cells based on scRNA-seq data using topic modeling (mental process/mathematical concept; the human mind is capable of computing/building a model based on data using topic modeling, and doing so is equivalent to performing a calculation to build a model; claim 1, 29)
Calculating at least one RNA velocity parameter (mental process/mathematical concept; the human mind is capable of calculating a parameter, and performing a calculation is a mathematical process; claim 1, 29)
Filtering the scRNA-seq data by removing genes that do not have spliced and unspliced transcripts in at least 20 cells of the plurality of cells (mental process; the human mind is capable of filtering data by removing data that do not fit a criteria; claim 2)
Applying a topic model to scRNA-seq data (mental process/mathematical concept; the human mind is capable of applying a model to data, and applying a model to data is a mathematical process; claim 3)
Calculating an optimal number of topics for the topic modeling (mental process/mathematical concept; the human mind is capable of calculating an optimal number of topics, and performing a calculation is a mathematical concept; claim 7)
Dependent claims 4-6 further limit the abstract ideas recited in the independent claims, and do not change their characterization as abstract ideas.
Therefore, the claims recite elements that constitute one or more judicial exceptions.
With regard to step (2A)(2) (Do the claims recite additional elements that integrate the judicial exception into a practical application?): No. Claim 1 and its dependents recite the additional element of receiving single cell RNA-sequencing data from each cell. Claim 29 also recites the additional element of a system comprising a database and computer processors coupled to the database for performing the steps of claim 1.
While the claims recite the additional element of receiving data, such steps that only amount to necessary data gathering for an analysis, without any technical details of how the data is obtained/output that integrate the judicial exception, are insignificant extrasolution activities that do not add a meaningful limitation to the claims (see MPEP 2106.05(g)). As a result, the judicial exception is not integrated into a practical application. In addition, while the claims recite additional elements related to the use of computers, they do not provide any specific details by which the computer, database or processor performs or carries out the judicial exception listed in step (2A)(1), nor do they provide any details of how specific structures of the computer are used to implement these functions. The judicial exception is therefore not integrated into a practical application because the generically recited computer elements do not add a meaningful limitation to the abstract idea, as they amount to simply implementing the abstract idea on a computer (see MPEP 2106.05(f)). Because the claims do not recite any additional elements that integrate the judicial exception into a practical application, the claims as a whole are directed to an abstract idea.
With regard to step (2B) (Do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?): No. The claims recite an abstract idea with additional elements; however, these additional elements are general computer elements added to abstract ideas, and non-particular instructions to apply the abstract idea by linking it to a field of use or extrasolution activity (see MPEP 2106.05(f-h)). General computer elements used to perform an abstract idea do not provide an inventive concept, and similarly, non-particular instructions to gather or produce data for analysis do not provide an inventive concept. Non-particular instructions to gather or receive data are also considered well-understood, routine and conventional activities (see MPEP 2106.05(d), which indicates that limitations such as “Receiving or transmitting data over a network” from Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362, “Storing and retrieving information in memory” from Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, and “Amplifying and sequencing nucleic acid sequences”, from University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014) are recognized as conventional activities). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As a result, the claims as a whole do not provide an inventive concept.
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.
Claim Rejection
Claims 1, 3 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by DANI 2021 “A cellular and spatial map of the choroid plexus across brain ventricles and ages.”
Claim Interpretation and Scope and Contents of Prior Art
Claim 1 recites a method of building a model of cellular trajectory in a plurality of cells, the method comprising receiving single cell RNA-sequencing (scRNA-seq) data from each cell in the plurality of cells; and computing the model for the plurality of cells based on the scRNA-seq data using topic modeling and calculating at least one RNA velocity parameter.
With respect to these limitations, DANI teaches modeling cell trajectory in the choroid plexus (Abstract, pg 3060) comprising receiving scRNA-seq data from single cells (3058 col 2, Fig 1) and building the model using topic modeling based on the scRNA data (pg 3062). DANI further teaches using RNA velocity analysis to calculate RNA velocity parameters (pg e7 last par and e8 par 1, Fig S2).
Claim 3 recites the limitation wherein the topic modeling comprises applying a topic model to the scRNA-seq data. With respect to this limitation, DANI teaches applying a topic model to the scRNA data (pg 3062).
Claim 29 recites a system for building a model of cellular trajectory in a plurality of cells, comprising: a database storing single cell RNA-sequencing (scRNA-seq) data; and
one or more computer processors operatively couple to said database wherein said one or
more computer processors are individually or collectively programmed to perform the steps of
claim 1. With respect to these limitations, DANI teaches that scRNA-seq data is stored in a database and its method performed using general computer elements (pg e3, e6-e8).
Claim Rejections - 35 USC § 103
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.
Claim Rejection
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over DANI 2021 as applied to claims 1, 3 and 29 in the 102 rejection above, in view of LA MANNO 2018 “RNA velocity of single cells” (as cited on the IDS filed 05/22/2023) and LUECKEN 2019 “Current best practices in single-cell RNA-seq analysis: a tutorial.”
Claim Interpretation and Scope and Contents of Prior Art
DANI teaches the limitations of claims 1, 3 and 29 in the 102 rejection above.
Claim 2 recites the limitation wherein the scRNA-seq data is filtered by removing genes that do not have spliced and unspliced transcripts in at least 20 cells of the plurality of cells. DANI does not teach this limitation, however LA MANNO teaches filtering scRNA-seq data by removing genes that do not have a certain amount of spliced and unspliced molecules and clusters with less than 120 cells (pg 11 par 2, pg12 par 1) and LUECKEN teaches that pre-processing of scRNA-sec data teaches using a minimum cell cluster size threshold that scales with the number of cells in the dataset and intended downstream analysis, which can involve filtering out genes expressed in fewer than 20 cells as an example (pg 3 last par, p4 par 1).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in processing scRNA-sec data for RNA velocity analysis would have been motivated to combine the teachings of DANI with the teachings of LA MANNO and LUECKEN, in order to achieve the claimed invention, because RNA velocity can be directly estimated by distinguishing unspliced and spliced mRNAs (LA MANNO Abstract) and because setting a minimum cell cluster size threshold is important for quality control (LUECKEN pg 3 last par). A person of ordinary skill would reasonably expect success from combining these teachings, as DANI, LA MANNO and LUECKEN teach single-cell RNA-seq analysis, and the preprocessing steps of LA MANNO and LUECKEN can be added to the analysis steps of DANI to produce high quality data specifically for determining RNA velocity. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over DANI 2021 as applied to claims 1, 3 and 29 in the 102 rejection above, in view of WU 2021 “Penalized Latent Dirichlet Allocation Model in Single‑Cell RNA Sequencing.”
Claim Interpretation and Scope and Contents of Prior Art
DANI teaches the limitations of claims 1, 3 and 29 in the 102 rejection above.
Claim 4 recites the limitation wherein the topic model comprises a multinomial topic model. With respect to this limitation, DANI teaches performed topic modeling using Latent Dirichlet Allocation (LDA) (pg e7 par 2) but does not teach that this is multinomial. However, WU teaches an LDA model for scRNA-seq data that is a multinomial topic model (pg 547).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in multinomial topic models would have been motivated to combine the teachings of DANI with the teachings of WU, in order to achieve the claimed invention, because LDA topic models can be multinomial, and can be applied to scRNA-seq data for cell analysis (pg 547). A person of ordinary skill would reasonably expect success from combining these teachings, as both DANI and WU teach methods of using LDA models for analysis of scRNA-seq data, and the multinomial model of WU can be used in place of or alongside the unspecified LDA model of DANI. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over DANI 2021 as applied to claims 1, 3 and 29 in the 102 rejection above, in view of GAN 2021 “Selection of the Optimal Number of Topics for LDA Topic Model—Taking Patent Policy Analysis as an Example.”
Claim Interpretation and Scope and Contents of Prior Art
DANI teaches the limitations of claims 1, 3 and 29 in the 102 rejection above.
Claim 7 recites the limitation wherein an optimal number of topics is calculated for the topic modeling. DANI does not teach this limitation; however, GAN teaches methods for determining the optimal number of topics for an LDA topic model (Abstract), which DANI uses.
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in using LDA topic models for analysis would have been motivated to combine the teachings of DANI with the teachings of GAN, in order to achieve the claimed invention, because selecting the optimal number of topics results in several improvements to the model/analysis, including good predictive ability, high isolation between topics, no duplicate topics, and repeatability for the model (Abstract). A person of ordinary skill would reasonably expect success from combining these teachings, as both DANI and GAN teach using LDA topic models for analysis, and because the selection process of GAN can be applied to the LDA topic model of DANI for model improvement. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over DANI 2021 as applied to claims 1, 3 and 29 in the 102 rejection above, in view of GORIN 2020 “Special function methods for bursty models of transcription.”
Claim Interpretation and Scope and Contents of Prior Art
DANI teaches the limitations of claims 1, 3 and 29 in the 102 rejection above.
Claim 10 recites the limitation wherein calculating at least one RNA velocity parameter comprises an RNA velocity parameter estimation by a geometric burst model. DANI does not teach this limitation, however GORIN teaches RNA velocity parameter estimation using a geometric burst model (pg 2-4).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in RNA velocity parameter estimation would have been motivated to combine the teachings of DANI with the teachings of GORIN, in order to achieve the claimed invention, because GORIN’s method of RNA velocity parameter estimation using a geometric burst model demonstrates effective control of precision and runtime in addition to parameter inference (Abstract). A person of ordinary skill would reasonably expect success from combining these teachings, as both DANI and GORIN teach methods of RNA velocity parameter estimation, such that the methods of GORIN can be substituted or used alongside the methods of DANI to produce an accurate result. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claims Without an Art Rejection
No art rejection is applied to claims 5-6. Close art, for example WU 2021 (as cited on the 892 and referred to above), while teaching LDA models and equations, does not teach the specific equations of claims 5-6, and no combinable art before the effective filing date could be found to render the claims as obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R. Skowronek can be reached at (571) 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY C LEVERETT/ Examiner, Art Unit 1687
