DETAILED ACTION
Applicant’s response, filed 25 Aug. 2026 has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 25 Aug. 2026 has been entered.
Status of Claims
Claims 1-38, 52, and 59 are cancelled.
Claims 39-51 and 53-58 are pending.
Claims 39-51 and 53-58 are rejected.
Priority
Applicant’s claim for the benefit of a prior-filed application, U.S. Provisional App. No. 62/865,033 filed 21 June 2019, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Accordingly, the effective filing date of the claimed invention is 21 June 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 26 Aug. 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the list of cited references was considered in full by the examiner.
Claim Interpretation
Claim 39 recites “providing single-cell ribonucleic acid (RNA) sequence data for a plurality of diseased cells and a plurality of normal cells of a cell type…”, which under the broadest reasonable interpretation of the claim, is interpreted to encompass inputting/providing already generated single-cell RNA sequence data (e.g. by a computer), but the claim does not require a step of physically sequencing a sample to generate the sequence data.
Claim 39 recites “wherein said plurality of diseased cells and said plurality of normal cells are differently differentiated from a same cell type such that…”. The limitation regarding how the diseased cells and normal cells were differently differentiated from a same cell type is interpreted to be a product by process limitation defining the process in which the diseased and normal cells were derived. See MPEP 2113 I.
Claim Interpretation-35 USC § 112(f)
The following interpretation is previously recited.
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitations are:
a genomic editing unit, used for editing one or more genomic regions in a cell in clam 39.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
Applicant’s specification at para. [0014] discloses the “genomic editing unit” is a CRISPR system, a CRISPRi system, a CRISPRa system, an RNAi system, or an shRNA system. Therefore the genomic editing unit will be interpreted to be one of these systems, including equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112(a)
The rejection of claims 39-59 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement in the Office action mailed 26 Feb. 2026 is withdrawn in view of Applicant’s claim amendments and cancellations received 25 Aug. 2026.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 44, 55, and 57 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. This rejection is newly recited after further consideration.
Claim 44 recites “wherein said same cell type is a precancerous cell type”, such that the diseased cells and normal cells are differently differentiated from the same “precancerous cell type”. Applicant’s specification at para. [0007] and [0018] discloses cell populations are derived from relevant tissues of healthy or diseased patients, or derived from primary cell lines, human organoids, animal models, or other appropriate model systems. Applicant’s specification at para. [0083] and [0086] also states the diseased cells and normal cells are “of a cell type”, the method re-programs the cell type between the first and second phenotypic state, and that the diseased cell types may be pancreatic cancer cells while the non-diseased cell types may be pancreatic cells such as pancreatic ductal or acinar cells (i.e. both are a pancreatic cell type). However, Applicant’s specification does not disclose the diseased cells and normal cells are differentially differentiated from a precancerous cell type.
Claims 55 and 57 recite “wherein the second phenotypic state is a senescent cell state” and “wherein said second phenotypic state is a precancerous cell state”, such that the normal cells comprise a senescent or precancerous cell state respectively. Applicant’s specification at para. [0038] and [0081] discloses the target state may be derived from healthy tissue or primary cell line, or alternatively, represent an intermediate state including senescent cells, stem cells, precancerous cells, or progenitor cells relevant to disease progression. Similarly, Applicant’s specification at para. [0083] discloses the second phenotypic state may be a non-diseased state (e.g. wild type or progenitor state), an earlier disease state (e.g. a precancerous state, an earlier-stage cancer state, or a precursor state), or an intermediate disease state. However, Applicant’s specification does not provide support for a plurality of normal cells that are precancerous or senescent (also see 112(b) rejection below).
For the reasons discussed above, the specification does not provide a sufficient disclosure of the limitations above recited in claims 44, 55, and 57 to demonstrate to one of ordinary skill in the art that the inventor possessed the invention at the time the application was filed. THIS IS A NEW MATTER REJECTION. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Response to Arguments
Applicant's arguments filed 25 Aug. 2026 regarding 35 U.S.C. 112(a) have been fully considered but they are not persuasive because they do not pertain to the new grounds of rejection set forth above.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 52 and 59 under 35 U.S.C. 112(b) in the Office action mailed 26 Feb. 2026 is withdrawn in view of the cancellation of these claims received 25 Aug. 2026
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.
Claims 39-51 and 53-58 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. This rejection is newly recited after further consideration of the claims.
Claim 39, and claims dependent therefrom, are indefinite for recitation of “a plurality of normal cells”. The term “normal” in claim 39 is a relative term which renders the claim indefinite. The term “normal” 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. In the instant case, the metes and bounds of what cells are intended to be considered “normal” are not clear, particularly since various dependent claims state the normal cells may be “precancerous” or “senescent”, suggesting “normal” does not merely mean healthy or non-diseased. Given one of ordinary skill in the art would not consider a precancerous or a senescent cell “normal”, this raises confusion regarding what Applicant intends to be “normal”. Applicant’s specification at para. [0083] discloses the second phenotypic state may be a non-diseased state, diseased state, or earlier disease state, suggesting “normal” is intended to refer to “non-diseased”. Clarification is requested via claim amendment. For purpose of applying prior art, the normal cells are interpreted to mean healthy cells, as suggested by Applicant’s specification, and a non-cancerous cells is interpreted to be precancerous given a non-cancerous cell does not have cancer.
Response to Arguments
Applicant's arguments filed 25 Aug. 2026 regarding 35 U.S.C. 112(b) have been fully considered but they are not persuasive because they do not pertain to the new grounds of rejection set forth above.
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.
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 39-40, 42-45, 48-51, 54, and 56-58 are rejected under 35 U.S.C. 103 as being unpatentable over Gong (2018) in view of Gross (2013) and Firas (2019). This rejection is newly recited and necessitated by claim amendment.
Cited references:
Gong et al., TCM visualizes trajectories and cell populations from single cell data, 2018, Nature Communications, pg. 1-8 (previously cited);
Gross et al. , Surprisal Analysis of Transcripts Expression Levels in the Presence of Noise: A Reliable Determination of the Onset of a Tumor Phenotype, 2013, PLOS ONE, 8(4), pg. 1-6 (newly cited); and
Firas, US 2019/0017032 A1; Pub. Date: 2019 Jan. 17 (newly cited).
Regarding claim 39, Gong discloses a method of analyzing expression trajectories between cell subpopulations (Abstract) comprising the following steps:
Gong discloses providing single-cell RNA (scRNA) sequencing data for a plurality of cell types derived from multiple lineages (i.e. cells differentiated from a same cell type given they are derived from a lineage) (pg. 2, col. 1, para. 1; pg. 3, col. 1, para. 2 to col. 2, para. 1, e.g. scRNA-seq datasets with cell types from multiple lineages; pg. 4, col. 2, para. 1, e.g. germline and somatic cells analyzed; Fig. 3; Fig. 4, e.g. iPSCs to cardiomyocyte differentiation).
Gong discloses mapping the scRNA sequencing data into a latent space (Fig. 3-4).
Gong discloses constructing developmental trajectories following the differentiation of the cells from one type to another cell types, wherein the trajectories define changes in gene expression patterns during differentiation (Fig. 2-3; pg. 3, col. 1, para. 3; pg. 5, col. 1, para. 3 to col. 2, para. 1).
Gong further discloses identifying genes (i.e. one or more genomic regions) with increased or decreased expression along the trajectory to characterize particular cell populations (pg. 4, col. 2, para. 2; pg. 5, col. 1, para. 3 to col. 1, para. 1). The limitation “for therapeutic targeting” is considered an intended use of the identified genomic regions.
Gong does not disclose the following limitations:
Regarding claim 39, Gong does not disclose the cell types comprise a plurality of diseased cells, that the trajectory is between the first phenotype state of the diseased cells and the second phenotypic state of normal cells.
However, Gross discloses a method of analyzing transcript expression levels of mRNA over time for the identification of the onset in time of a cancer phenotype (Abstract), which includes obtaining expression levels measured at different points in time and spanning many cell divisions and then analyzing the ongoing changes ( pg. 1, col. 1, para. 1). Gross discloses analyzing the expression changes over time when the cells are normal, progress to tumor cells, and then metastasize to identify transcriptional patterns indicative of the onset of cancer (Figures 3-4; pg. 4, col. 2, para. 3 to pg. 5, col. 1, para. 1; pg. 5, col. 2, para. 3). Gross discloses identifying transcription patterns that account for healthy cell pathways, such as apoptosis, that need to be switched off in cancer cells, and further discloses the method allows a determination of the presence of a cancer forewarning (Abstract; pg. 2, col. 1, para. 2).
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 of Gong to have analyzed a transcription trajectory between diseased and normal cells, as shown by Gross above. One of ordinary skill in the art would have been motivated to combine the methods of Gong and Gross in order to facilitate the identification of pathways required to be switched off in cancer cells, thus providing a forewarning to cancer, as shown by Gross (Abstract; pg. 2, col. 1, para. 2). This modification would have had a reasonable expectation of success because both Gong and Gross analyze transcriptional trajectories between cell types, and thus the method of Gong could be applied to the healthy and diseased cells of Gross.
Further regarding claim 39, Gong in view of Gross does not disclose performing a genetic screening for therapeutic targeting, wherein said genetic screening comprises editing, using a genomic editing unit, said one or more genomic regions in a cell comprising said first phenotypic state.
However, Firas discloses a method for reprogramming a diseased source cell to a normal target cell based on determining transcription factors required for conversion for cell-based regenerative therapy (Abstract; [0347]; [0357 and Table 4)), which comprises determining differential expression of genes in the source and target cell types and identifying a set of transcription factors for conversion of the diseased cell to normal cell, based on the differential gene expression (claim 1; [0013]). Firas further discloses screening candidate agents for an ability to increase the required transcription factors for conversion, and using an agent to reprogram the diseased source cell by delivering genetic material encoding relevant transcription factors required for the conversion into the diseased source cells, wherein each transcription factor is introduced into the diseased source cells as a polynucleotide transgene encoding the transcription factors to increase protein expression ([0364 and [0366]]; [0379]-[0380]). Firas further discloses the agent for reprogramming may be RNAi agent (as interpreted under 35 U.S.C. 112(f) above) ([0305]; claim 14). Firas discloses the target cells may be used to treat a medical condition in an individual ([0368]).
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 of Gong in view of Gross to have performed a genetic screening by editing a differentially expressed gene of a diseased cell, as shown by Firas above. One of ordinary skill in the art would have been motivated to combine the methods of Gong and Firas in order to shift diseased cells to a normal state, thus treating or preventing a medication condition in an individual, as shown by Firas ([0368]), given Gross discloses identifying transcription patterns that must be turned off in healthy cells for disease progression (Abstract). This modification would have had a reasonable expectation of success because Gong identifies genes with increased or decreased expression (i.e. differentially expressed genes) along a trajectory to characterize particular cell populations (pg. 4, col. 2, para. 2; pg. 5, col. 1, para. 3 to col. 1, para. 1), which are applicable to the method of Firas which uses differentially expressed genes to identify transcription factors for reprogramming.
Regarding the dependent claims:
Regarding claim 40, Gong further discloses the mapping comprises using dimensionality reduction (pg. 2, col. 1, para. 2 and col. 2, para. 1-2).
Regarding claims 42-43, Gong discloses the cells may be derived from cell lines generated from induced pluripotent stem cells (pg. 5, col. 1, para. 3 to col. 2, para. 1).
Regarding claim 44¸ Gong in view of Gross and Firas make obvious the normal and diseased cells as applied to claim 39 above. Gross discloses the diseased cells are cancer cells, and analyzes transcription throughout a precancerous state (Figures 3-4; pg. 4, col. 1, para. 3), such that the different cell types derived from a lineage of Gong in view of Gross and Firas necessarily include a precancerous cell (i.e. along the trajectory of normal to cancerous cell).
Regarding claim 45, Gong discloses the various cell types may be derived from induced pluripotent stem cells (pg. 5, col. 1, para. 3 to col. 2, para. 1). Given the normal and diseased cells along a trajectory of Gong in view of Gross and Firas are differentiated, the cell types are necessarily derived from a common progenitor.
Further regarding claims 42-45, it is noted the limitations only serve to define the process in which the diseased cells and normal cells were previously derived from a same cell type. Gong in view of Gross and Firas discloses the normal and diseased cells derived from the same cell type along a trajectory as applied to claim 39 above, and therefore the product of Gong in view of Gross and Firas is the same as those in the claims, regardless of whether the cells were derived from a cell line, stem cell type, precancerous cell type, or progenitor cell type, particularly given Gong discloses the different cell types are of a lineage.
Regarding claim 48, Gong discloses identifying genes (i.e. genomic regions) with increased or decreased expression along the trajectory to characterize particular cell populations (pg. 4, col. 2, para. 2; pg. 5, col. 1, para. 3 to col. 1, para. 1), such that the editing of Gong in view of Gross and Firas, as applied to claim 39, would be performed for multiple genes. It is noted that Firas also discloses determining multiple genes for reprogramming (claims 1 and 11).
Regarding claim 49¸ Gong discloses gene expressions of the genes vary over time according to non-temporal factors, ranging from 0% to 100% variance in expression not associated with time a (Figure 1). This demonstrates the non-linear nature of the gene interactions given some gene expressions increase more or less than would be expected based on expression over time. Gone further discloses the genes interact with each other temporally (i.e. hierarchically/in order) (Fig. 1).
Regarding claim 50, Gong in view of Gross and Firas make obvious the normal and diseased cells as applied to claim 39 above. Gross discloses the diseased cells are cancerous cells (Figures 3-4) and the normal cells are healthy (i.e. wild-type) (pg. 2, col. 1, para. 2; Figures 3-4).
Regarding claim 51, Gong in view of Gross and Firas disclose the genomic editing unit is an RNAi system, as applied to claim 39 above.
Regarding claim 54, Gong further discloses generating the scRNA sequencing data for the cell types by simulating the scRNA sequencing data (pg. 3, col. 1, para. 2).
Regarding claim 56, Gong in view of Gross and Firas make obvious the normal and diseased cells as applied to claim 39 above. Firas further discloses the target cell (i.e. normal cells) may be stem cells ([0049]).
Regarding claim 57, Gong in view of Gross and Firas make obvious the normal and diseased cells as applied to claim 39 above. Given the cells are normal, or non-diseased, they are considered precancerous as discussed in the 112(b) rejection above ([0049]).
Regarding claim 58, Gong in view of Gross and Firas make obvious the normal and diseased cells as applied to claim 39 above. Firas further discloses the target cell (i.e. normal cells) may be a precursor cell (i.e. progenitor cell) ([0049]).
Claims 41, 46-47, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Gong in view of Gross and Firas, as applied to claim 39-40 above, and further in view of Lotfollahi (2018). This rejection is newly recited and necessitated by claim amendment.
Cited reference: Lotfollahi et al., Generative modeling and latent space arithmetics predict single-cell perturbation response across cell types, studies and species, 2018, bioRxiv, pg. 1-27 (newly cited).
Regarding claims 41, 46-47, and 53, Gong in view of Gross and Firas disclose the method of claims 39-40, as applied above.
Regarding claims 41 and 46-47, Gong in view of Gross and Firas, as applied to claims 39-40 above, does not disclose the dimensionality reduction algorithm for the mapping comprises a UMAP algorithm, or that the mapping is performed using a neural network comprising an autoencoder.
Regarding claim 53, Gong in view of Gross and Firas, as applied to claim 39 above, does not disclose measuring, using an anomaly detection algorithm, a quantify of a shift in said latent space responsive to said editing.
However, regarding claims 41 and 46-47, Lotfollahi discloses a method for predicting single-cell perturbation responses across cell types (Abstract), which includes using an autoencoder to map single-cell transcriptomics data of different cell types to a latent space (Figure 1; pg. 2, para. 2) and visualizing the latent space using a UMAP algorithm (Figure 2; Suppl. Figure 4).
Regarding claim 53, Lotfollahi further discloses estimating perturbations (i.e. shifts) in the latent space in perturbed cells relative to unperturbed cells (Figure 1), wherein the perturbed cells comprise knock-out of genes (i.e. gene editing) (pg. 1, para. 2). Lotfollahi discloses a group of cell perturbation responses may result in expression-level changes that are shred across all cell types or unique to only one, and inferring both types is essential for understanding mechanisms involved in disease progression (pg. 5, para. 4).
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 mapping of single-cell transcription data to a latent space of Gong in view of Gross and Firas to have utilized an autencoder and UMAP algorithm, as shown by Lotfollahi above. One of ordinary skill in the art would have been motivated to combine the methods of Gong in view of Gross and Firas with Lotfollahi based on the simple substitution of the dimensionality reduction algorithm of Gong, as applied to claim 40, with the dimensional reduction method using an autoencoder and UMAP algorithm of Lotfollahi. One of ordinary skill in the art would recognize the autoencoder and UMAP algorithm of Lotfollahi would have been used in the method of Gong and obtained predictable results, given both Gong and Lotfollahi utilize dimensionality reduction algorithms and visualize to analyze single cell transcriptomics data of a plurality of cell types, and furthermore, because Gong explores using a plurality of different dimensionality reduction algorithms (Fig. 4, e.g. see different methods for producing latent space).
It would have been further prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have modified the method of Gong in view of Gross and Firas, as applied to claim 39 above, further to have measured a quantify of a shift in the latent space responsive to editing, as shown by Lotfollahi above. One of ordinary skill in the art would have been motivated to combine the methods of Gong in view of Firas with Lotfollahi in order to facilitate the understanding of mechanisms involved in disease progression, as shown by Lotfollahi (pg. 5, para. 4), given Gong in view of Firas relate to analyzing transcriptomic trajectories from a diseased cell to a normal cell. There would have been a reasonable expectation of success given both Gong and Lotfollahi analyze single-cell transcriptomics data in a latent space.
Therefore the invention is prima facie obvious.
Claim 55 is rejected under 35 U.S.C. 103 as being unpatentable over Gong in view of Gross and Firas, as applied to claim 39 above, and further in view of Saab (2011). This rejection is newly recited and necessitated by claim amendment.
Cited reference: Saab, Senescence and pre-malignancy: How do tumors progress?, 2011, 21, pg. 385-391 (newly cited).
Regarding claim 55, Gong in view of Gross and Firas disclose the method of claim 39 above.
Gong in view of Gross and Firas, as applied to claim 39 above, does not disclose the second phenotypic state is a senescent cell state. However, as discussed above with respect to claim 39, Gong in view of Gross disclose analyzing the transition from normal cells to precancerous to cancerous cells and metastatic cells.
Furthermore, Saab overviews the role of senescence in pre-malignancy and tumor progression (Abstract), and discloses that premalignant lesions may progress to cancer by a version from a senescent cell state, and that under oncogenic stress a cell may successfully undergo cell cycle exit and activate a senescence response, but may later escape from the established senescent state through disruption of pathways responsible for maintenance of senescence (Figure 1; pg. 388, col. 1, para. 2; pg. 389, col. 1, para. 3 to col. 2, para. 1). Saab further discloses understanding the molecular pathways underlying the senescence phenotype holds promise for better identification of those most likely to progression into cancer and development of therapies for inducing or maintaining senescence (pg. 389, col. 2, para. 3-4).
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 transcription trajectory between a diseased and normal cell type of Gong in view of Gross and Firas, to have analyzed the transition between the diseased cell type and a senescent cell type, as shown by Saab above. One of ordinary skill in the art would have been motivated to combine the methods of Gong in view of Gross and Firas with Saab in order to identify pathways responsible for maintenance of senescence to avoid tumor progression, as shown by Saab (Figure 1; pg. 388, col. 1, para. 2; pg. 389, col. 1, para. 3 to col. 2, para. 1), thus aiding in the determination of the presence of a cancer forewarning as shown by Gross (Abstract; pg. 2, col. 1, para. 2). This modification would have had a reasonable expectation of success because Gong in view of Gross similarly discloses identifying transcription patterns that account for healthy cell pathways, such as apoptosis, that need to be switched off in cancer cells (Gross: Abstract; pg. 2, col. 1, para. 2), and thus the method of Gong could be applied to analyze transcription trajectories between cancerous and senescent cells.
Therefore, the invention is prima facie obvious.
Double Patenting
The provisional rejection of claims 39-41 50-54, and 59 on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of copending Application No. 18/206,981 (reference application) in the Office action mailed 26 Feb. 2026 has been withdrawn in view of the terminal disclaimer filed 25 Aug. 2026 and accepted 02 Sept. 2026.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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The following rejections are newly recited after further consideration of the claims.
Claims 39-51, 53-54, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. US 11,710,536 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because
Reference claim 1 discloses the limitations of instant claim 39. It is noted that reference claim 1 is narrower than instant claim 39 and therefore anticipates instant claim 39.
Reference claims 2-4 disclose the limitations of instant claims 40-41
Regarding instant claims 42-45, the limitations only serve to define the process in which the diseased cells and normal cells were previously derived from a same cell type. The reference claims discloses the normal and diseased cells derived from the same cell type along a trajectory as applied to claim 39 above, and therefore the product of the reference claims is the same as those in the claims, regardless of whether the cells were derived from a cell line, stem cell type, precancerous cell type, or progenitor cell type.
Regarding instant claims 46, reference claim 14 discloses the use of a neural network.
Regarding instant claim 47, reference claim 1 discloses the sequence data is mapped to a latent space, while reference claim 14 discloses this is done by a neural network, which makes obvious the use of an autoencoder for mapping data to a latent space.
Regarding instant claim 48, reference claim 1 discloses identifying one or more regions based on expression data, which makes obvious identifying a plurality of genes.
Regarding instant claim 49¸ reference claim 1 discloses reconstructing a nonlinear cell trajectory using the expression data.
Regarding instant claim 50, reference claim 8 discloses this limitation.
Regarding instant claim 51, reference claim 10 discloses this limitation.
Regarding instant claim 53, reference claims 16-17 disclose this limitation.
Regarding instant claim 54, reference claim 19 discloses this limitation.
Regarding instant claim 57, reference claim 21 discloses the cells include an intermediate phenotypic state, and reference claim 8 discloses the states are a cancer and a wild-type state, demonstrating an intermediate state is a precancerous state.
Claim 55 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. US 11,710,536 B2, as applied to claim 39 above, further in view of Saab (2011)
Cited reference: Saab, Senescence and pre-malignancy: How do tumors progress?, 2011, 21, pg. 385-391 (newly cited).
Regarding instant claim 55, the reference claims disclose method of claim 39 above.
The reference claims do not disclose the second phenotypic state is a senescent cell state. However, as discussed above with respect to claim 39, the reference claims disclose analyzing a transition from a wild type to cancerous cell state.
Furthermore, Saab overviews the role of senescence in pre-malignancy and tumor progression (Abstract), and discloses that premalignant lesions may progress to cancer by a version from a senescent cell state, and that under oncogenic stress a cell may successfully undergo cell cycle exit and activate a senescence response, but may later escape from the established senescent state through disruption of pathways responsible for maintenance of senescence (Figure 1; pg. 388, col. 1, para. 2; pg. 389, col. 1, para. 3 to col. 2, para. 1). Saab further discloses understanding the molecular pathways underlying the senescence phenotype holds promise for better identification of those most likely to progression into cancer and development of therapies for inducing or maintaining senescence (pg. 389, col. 2, para. 3-4).
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 of the reference claims to have analyzed the pathways for converting a senescent cell state to a diseased state, a shown by Saab above. One of ordinary skill in the art would have been motivated to combine the methods of the reference claims with Saab in order to better identify of those most likely to progression into cancer and therapies for inducing or maintaining senescence, as shown by Saab(pg. 389, col. 2, para. 3-4). This modification would have had a reasonable expectation of success given the reference claims also analyze genomic regions leading to a disease cell state.
Claims 56 and 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. US 11,710,536 B2, as applied to claim 39 above, further in view of Firas (2019).
Cited reference: Firas, US 2019/0017032 A1; Pub. Date: 2019 Jan. 17 (newly cited).
The reference claims disclose the method of claim 39 as applied above.
Regarding claims 55-56 and 68, the reference claims do not disclose the second phenotypic state is a stem cell state or a progenitor cell state.
However, Firas discloses a method for reprogramming a diseased source cell to a normal target cell based on determining transcription factors required for conversion for cell-based regenerative therapy (Abstract; [0347]; [0357 and Table 4)), which comprises determining differential expression of genes in the source and target cell types and identifying a set of transcription factors for conversion of the diseased cell to normal cell, based on the differential gene expression (claim 1; [0013]). Firas further discloses screening candidate agents for an ability to increase the required transcription factors for conversion, and using an agent to reprogram the diseased source cell by delivering genetic material encoding relevant transcription factors required for the conversion into the diseased source cells, wherein each transcription factor is introduced into the diseased source cells as a polynucleotide transgene encoding the transcription factors to increase protein expression ([0364 and [0366]]; [0379]-[0380]). Firas discloses the target cells may be stem cells or precursor (progenitor) cells ([0049]).
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 of the reference claims to have analyzed differentially expressed genes between a diseased cell and a stem cell or precursor cell, as shown by Firas above. One of ordinary skill in the art would have been motivated to combine the methods of the reference claims in order to shift diseased cells to stem cell or progenitor (non-diseased) state, thus treating or preventing a medication condition in an individual, as shown by Firas ([0368]), given the reference claims also reprogram cells. This modification would have had a reasonable expectation of success because the reference claims identify regions along a transcription trajectory for cell reprogramming, which are applicable to the method of Firas which uses differentially expressed genes to identify transcription factors for reprogramming.
Response to Arguments
Applicant's arguments filed 25 Aug. 2026 regarding double patenting have been fully considered but they are not persuasive because they do not pertain to the new grounds of rejection set forth above.
Conclusion
No claims are allowed.
Claims 39-51 and 53-58 are patent eligible for the reasons discussed in the Office action mailed 11 June 2025.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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