DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-5 are pending and examined herein.
No claims are canceled.
Priority
As detailed on the 02 May 2023 filing receipt, the application claims priority as early as 08 April 2022 to provisional application 63/329,266. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
Information disclosure statement (IDS) was filed on 05 May 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other forms of browser-executable code (paragraphs [102 and 105]). 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 1 and 4-5 are objected to because of the following informalities: the claims contain periods other than at the ends of sentences. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation (37 CFR 1.75(i)). Parentheses are an option which may be used to overcome the objection rather than periods.
Appropriate correction is required.
Claim Interpretation
Claim 5 recites selecting an immune checkpoint blockade treatment if the assigned cell state is indicative of an immune-enriched tumor and selecting an active targeting of a molecular pathway specific to a signal if indicative of a less differentiated tumor. Therefore, if neither an immune enriched tumor nor a genomically less differentiated tumor is indicated, then a selecting step does not appear to be required. The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. MPEP 2111.04(II) pertains.
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 1-5 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements individually and in combination, are directed to a judicial exception at Step 2A, Prong 2, and the additional elements of the claims, considered individually and in combination, do not provide significantly more at Step 2B than the abstract idea of selecting a treatment based on cell state.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a method (claims 1-5), which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Claim 1 recites transforming the bulk RNA sequencing sample into a cell state fraction dataset comprising cell states and proportion of expression attributable to each cell state. This step is interpreted as a data transformation, where the data is reorganized, under a broadest reasonable interpretation, by mental and/or mathematical steps.
Claim 1 recites assigning a cell state to the patient based on the cell fraction dataset. Assigning data is a step of data evaluation and opinion and thus a step practically performed by the human mind.
Claims 1 and 5 recite selecting a treatment, where making a selection is a step practically performed by the human mind.
Claim 2 recites additional information about the data cells, which is considered data per se and thus abstract.
Claim 3 recites additional information about the data cells in the form of a predicted clinical outcome, which is additional data and thus abstract.
Claim 4 recites an additional data transformation step, data assigning step, and a data association step based on data interpretation regarding the clinical outcomes, and thus also directed to mental steps.
Thus, the claims recite abstract ideas and thus must be examined further to determine whether elements in addition to the abstract ideas integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Because the claims recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they recite elements in addition to the abstract ideas which integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(III)).
Additional elements that are not abstract ideas recited in the claims include: a computer (claim 1), receiving a scRNA-seq dataset and an RNA sequencing sample (claim 1), and receiving calibration sequencing data sets and clinical outcomes (claim 4).
Steps reciting receiving data are a data gathering step required for the abstract steps, and thus is interpreted as insignificant extra-solution activity (MPEP 2106.05(g)). The recitation of a computer in the form of a “computer-implemented method” is considered a generic computer performing the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Thus, the claims recite elements in addition to the abstract ideas which do not integrate the abstract ideas into a practical application, and must be examined further to determine whether elements in addition to the abstract ideas provide significantly more (MPEP 2106.05). [Step 2A Prong One: Yes]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Additional elements that are not abstract ideas recited in the claims include: a computer (claim 1), receiving a scRNA-seq dataset and an RNA sequencing sample (claim 1), and receiving calibration sequencing data sets and clinical outcomes (claim 4).
The courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 (storing and retrieving information in memory), as discussed in MPEP 2106.05(d)(II)(i)).
The claims recite a computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Storing data on a computer is a conventional computer function (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; MPEP 2106.05(d)).
Therefore, the recited additional elements, alone or in combination, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Regev (US 20210358573 A1; newly cited) in view of Peng (Cell Research 29: 725-738, 2019; previously cited on the 06 May 2025 IDS form) and Chu (bioRxiv 897900, 45 pgs., 2021; newly cited).
Claim 1 recites receiving, at a computing device, a single-cell RNA sequencing (scRNAseq)
dataset comprising at least one RNA expression signature and associated cell state and a bulk RNA sequencing sample derived from a tumor sample obtained from the patient and transforming, using the computing device, the bulk RNA sequencing sample into a cell state fraction dataset comprising a plurality of cell states and associated proportion of the expression of the scRNA-seq dataset attributable to each cell state.
Regev teaches determining genetic signatures discovered by expression of single cells and determining cell state by applying the signature to bulk sequencing in a sample (paragraph [127]). Regev teaches clustering based on expression (paragraph [39]).
Claim 1 recites assigning, using the computing device, one tumor microenvironment (TME) cell state from a TME dataset to the patient based on the cell fraction dataset.
Regev teaches the signatures may be microenvironment specific to cell states (paragraph [127]) and obtaining a microenvironment (reference claim 1).
Claim 1 recites selecting a treatment for the patient based on the assigned TME cell state.
Regev recites the presence of specific cell types being susceptible to different treatments (paragraph [127]).
Regev does not teach a proportion of expression per cell as cell state fraction nor application to pancreatic adenocarcinoma; Regev teaches breast duct carcinoma (abstract).
Peng teaches application of single-cell RNA-seq to pancreatic adenocarcinoma (abstract).
Chu teaches cell type fraction or cell state among tumor types (Fig. 2).
Claim 2 recites TME cell state of the TME dataset comprises a unique distribution of cell fractions among the plurality of cell state categories.
Chu teaches cell type fractions differing among states (Fig. 5b).
Claim 3 recites each TME cell state further comprises a predicted clinical outcome associated with each TME cell state.
Chu teaches TME can be useful as biomarkers and as therapeutic targets (pg. 2, first paragraph) and clinical outcomes (abstract) as survival associated pathways as better or worse prognosis based on TME (Fig. 4), where cell type fraction is associated with TME.
Claim 4 recites producing a TME dataset by: receiving, at the computing site, a plurality of calibration single-cell RNA sequencing (scRNA-seq) datasets and associated clinical outcome measurements obtained from at least one PDAC patient population; transforming, using the computing device, each calibration scRNA-seq dataset into a calibration cell fraction dataset comprising a plurality of cell states and associated proportion of the expression of the scRNA-seq dataset attributable to each cell state; assigning, using the computing device, the plurality of calibration cell fraction datasets to a TME cell state of the TME dataset, wherein the TME cell state comprises a cell fraction distribution shared by all calibration cell fraction datasets assigned to the TME cell state, and associating, using the computing device, a clinical outcome to the TME cell state, the clinical outcome comprising the shared clinical outcome associated with all calibration cell fraction datasets assigned to the TME cell state.
Chu teaches an scRNA-seq reference (pg. 22, first paragraph) and reference corresponding tumor types and profiles by clustering based on heterogeneity, performing dimensionality reduction, and defining states (pg. 25, last paragraph; pg. 26, first paragraph). Chu teaches survival associated pathways as better or worse prognosis (Fig. 4).
Peng teaches application to PDAC and PDAC outcome (pg. 731, col. 1, second paragraph).
Claim 5 recites selecting a treatment for the patient based on the assigned TME cell state comprises: selecting an immune checkpoint blockade treatment if the assigned TME cell state is indicative of an immune-enriched tumors and selecting a treatment comprising administration of an active compound targeting a molecular pathway specific to an immature malignant cell state if the assigned TME cell state is indicative of a genomically less differentiated tumor.
Regev teaches treatments which block immune checkpoints (paragraph [196]) and an inhibitor for use against maturing or differentiating (paragraph [225]).
Combining Regev, Peng, and Chu
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of Regev, which is directed to molecular spatial maps for cancers using single cell RNA sequencing to determine subtypes for more effective therapy (abstract) with the work of Peng because Peng teaches specific application to pancreatic adenocarcinoma (abstract) whereas Regev teaches a different cancer, specifically types of breast cancer. Both Regev and Peng are directed to the shared field of endeavor of application of single-cell RNA sequencing and bulk RNA sequencing to tumor microenvironments and thus would be prima facie obvious to combine. Further combination with Chu, which teaches expression as related to cell type fractions, which would be desirable in combination because cell type fraction is associated with prognosis (Fig. 2). Chu is associated with the shared field of endeavor of associating expression patterns derived from scRNA-seq and bulk RNA-seq with tumor types, microenvironments, and clinical outcomes (abstract), and would also be prima facie obvious to combine with the works of Regev and Peng.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/Robert J. Kallal/Examiner, Art Unit 1685
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