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 .
Applicant filed a response dated 9/19/2025 in which claims 1, 4, 24, 34, and 43 have been amended, claims 12 and 25-33 have been canceled. Thus, the claims 1-11, 13-24, and 34-51 are pending in the application.
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 1-11, 13-24, and 34-51 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of quantitative systems pharmacology without significantly more.
Examiner has identified claim 43 as the claim that represents the claimed invention presented in independent claims 1, 34, and 43.
Claim 43 is directed to a system, which is one of the statutory categories of invention (Step 1: YES).
The claim 43 describes a system, comprising: a singular microphysiological systems (MPS) platform comprising one or more disease models; and a computing device comprising at least one processor and a memory operably coupled to the at least one processor, wherein the memory has computer-executable instructions stored thereon that, when executed by the at least one processor, cause the at least one processor to: analyze RNA sequencing (RNA-seg) data for a plurality of patients having a disease, wherein the analysis identified a plurality of differentially expressed genes (DEGs) and a plurality of differentially enriched biological pathways; derive a plurality of gene expression signatures with each of a plurality of disease states of the disease using the DEGs and the differentials enriched biological pathways; identify a plurality of drugs predicted to reverse a particular gene expression signature associated with a particular disease state of the disease; and prioritize for further experimental testing the drugs predicted to normalize the particular gene expression signature and/or physiological characteristic associated with the particular disease state of the disease, wherein the MPS platform is configured for testing a drug or combination of drugs selected from the drugs predicted to normalize the particular gene expression signature associated with the particular disease state of the disease, wherein said testing comprises one or more of RNA sequencing and one or more of obtaining panels to measure physiologically relevant metrics to demonstrate the inhibition or reversal of disease state in the one or more disease models, or identification of one or more biomarkers for a disease state of the disease. These limitations (with the exception of italicized limitations), under their broadest reasonable interpretation, describe the abstract idea of quantitative systems pharmacology. Furthermore, if a claim limitation, under its broadest reasonable interpretation, covers interactions between people, then it falls within the “certain methods of organizing human activity” grouping of abstract ideas. The additional elements of a singular microphysiological systems (MPS) platform, a computing device, a processor, a memory, and computer-readable instructions do not necessarily restrict the claim from reciting an abstract idea. Thus, the claim 43 recites an abstract idea (Step 2A-Prong 1: YES).
This judicial exception is not integrated into a practical application because the additional elements of a singular microphysiological systems (MPS) platform, a computing device, a processor, a memory, and computer-readable instructions result in no more than simply applying the abstract idea using generic computer elements. The additional elements of a singular microphysiological systems (MPS) platform, a computing device, a processor, a memory, and computer-readable instructions are recited at a high level of generality, and under their broadest reasonable interpretation comprises a generic computing device. The presence of a generic computing device does nothing more than to implement the claimed invention (MPRP 2106.05(f)). The additional limitations of a singular microphysiological systems (MPS) platform, a computing device, a processor, a memory, and computer-readable instructions are no more than mere instructions to apply the exception using a generic computer element. Therefore, the recitations of additional elements do not meaningfully apply the abstract idea and hence do not integrate the abstract idea into a practical application. Thus, the claim 43 is directed to an abstract idea (Step 2A-Prong 2: NO).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of a singular microphysiological systems (MPS) platform, a computing device, a processor, a memory, and computer-readable instructions are recited at a high level of generality in that it result in no more than simply applying the abstract idea using generic computer elements. The additional elements when considered separately and as an ordered combination do not amount to add significantly more as these limitations provide nothing more than to simply apply the exception in a generic computer environment (Step 2B: NO). Thus, the claim 43 is not patent eligible.
Similar arguments can be extended to other independent claims 1 and 34 and hence the claims 1 and 34 are rejected on similar grounds as claim 43.
Dependent claims 2-11, 13-23, 35-42, and 44-51 further define the abstract idea that is present in their respective independent claims 1, 34, and 43 and thus correspond to Certain Methods of Organizing Human Activity and hence are abstract in nature for the reasons presented above. Dependent claims do not include any additional elements that integrate the abstract idea into a practical application or are sufficient to amount to significantly more than the judicial exception when considered both individually and as an ordered combination. Therefore, the claims 2-11, 13-23, 35-42, and 44-51 are directed to an abstract idea. Thus, the claims 1-11, 13-24, and 34-51 are not patent-eligible.
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 1-5, 23-24, 34-35, 42-44, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Cirit et al., US Patent Application No. 2021/0156846 in view of Ghiassian et al., US Patent Application No. 2024/0203555.
Regarding claim 43, Cirit discloses a quantitative systems pharmacology (QSP) system, comprising:
a singular microphysiological systems (MPS) platform comprising one or more disease models (abstract; [0045], [0127]); and
a computing device comprising at least one processor and a memory operably coupled to the at least one processor, wherein the memory has computer-executable instructions stored thereon that, when executed by the at least one processor, cause the at least one processor to ([0123], [0140], [0142]):
analyze RNA sequencing (RNA-seq) data for a plurality of patients having a disease, wherein the analysis identifies a plurality of differentially expressed genes (DEGs) and a plurality of differentially enriched biological pathways ([0064], [0043], [0091], [0097]);
derive a plurality of gene expression signatures associated with each of a plurality of disease states of the disease using the DEGs and the differentially enriched biological pathways ([0091]);
identify a plurality of drugs predicted to reverse a particular gene expression signature associated with a particular disease state of the disease ([0093], [0097]); and
prioritize for further experimental testing the drugs predicted to normalize the particular gene expression signature and/or physiological characteristic associated with the particular disease state of the disease, wherein the MPS platform is configured for testing a drug or combination of drugs selected from the drugs predicted to normalize the particular gene expression signature associated with the particular disease state of the disease ([0112], [0127]),
wherein said testing comprises one or more of RNA sequencing and one of more of obtaining panels to measure physiologically relevant metrics to ([0018], [0046]-[0047], [0064]) demonstrate the inhibition of reversal of disease state in the one or more disease models, or identification of one or more biomarkers for a disease state of the disease.
Cirit does not specifically disclose
demonstrate the inhibition of reversal of disease state in the one or more disease models, or identification of one or more biomarkers for a disease state of the disease.
However, Ghiassian discloses
demonstrate the inhibition of reversal of disease state in the one or more disease models, or identification of one or more biomarkers for a disease state of the disease ([0005]-[0006]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit with the above-noted disclosure of Ghiassian. The motivation for combining these references would have been to treat the disease.
Regarding claim 44, Cirit discloses wherein the step of analyzing the RNA-seq data comprises:
mapping a plurality of gene expression values to a plurality of biological pathway expression profiles ([0091]); and
associating the biological pathway expression profiles with the disease states of the disease ([0124], [0126]).
Regarding claim 2, Cirit discloses where the disease is metabolic dysfunction associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD) (abstract, [0123]).
Regarding claim 4, Cirit discloses testing, using a microphysiological systems (MPS) platform, a drug or combination of drugs selected from the drugs predicted to normalize the particular gene expression signature and/or physiological characteristic associated with the particular disease state of the disease (abstract, [0093]).
Regarding claim 5, Cirit discloses mapping a plurality of gene expression values to a plurality of biological pathway expression profiles; and
associating the biological pathway expression profiles with the disease states of the disease.
Regarding claim 12, Cirit discloses reverses or halts the progression of the disease ([0007]).
Regarding claim 24, Cirit discloses a method for treating non-alcoholic fatty liver disease (NAFLD) comprising administering one or more of the drugs predicted to normalize the particular gene expression signature and/or physiological characteristic associated with the particular disease state of the disease as identified by the method of claim 1 to a subject in need thereof in an effective amount to decrease or inhibit the disease ([0007], abstract, [0123], [0140]-[0142], [0043], [0064], [0091], [0093], [0097], [0112]).
Ghiassian discloses
an effective amount to decrease or inhibit the disease ([0005]-[0006]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit with the above-noted disclosure of Ghiassian. The motivation for combining these references would have been to treat the disease.
Regarding claim 3, Cirit discloses entirely normal and steatosis, predominantly lobular inflammation, and predominantly fibrosis ([0093]).
Regarding claim 23, Cirit discloses identify a common thread for further experimental testing ([0005]).
Claims 1 and 34 are similar to claim 43 and hence rejected on similar grounds.
Claim 35 is substantially similar to claim 5 and hence rejected on similar grounds.
Claims 42 and 51 are substantially similar to claim 23 and hence rejected on similar grounds.
Claims 6-11, 13, 36-41, and 45-50 are rejected under 35 U.S.C. 103 as being unpatentable over Cirit in view of Ghiassian in view of Dammen et al., US Patent No. 2023/0220470.
Regarding claim 6, Daamen discloses using a gene set variation analysis (GSVA) algorithm ([0039]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Daamen. The motivation for combining these references would have been to treat the disease.
Regarding claim 7, Daamen discloses wherein the step of associating the biological pathway expression profiles with the disease states of the disease comprises using a clustering algorithm ([0129]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Daamen. The motivation for combining these references would have been to treat the disease.
Regarding claim 8, Daamen discloses wherein the step of identifying the drugs predicted to reverse the particular gene expression signature and/or physiological characteristic associated with the particular disease state of the disease comprises using a connectivity map (CMap) ([0360]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Daamen. The motivation for combining these references would have been to treat the disease.
Regarding claim 10, Daamen discloses using a network mapping algorithm ([0236]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Daamen. The motivation for combining these references would have been to treat the disease.
Regarding claim 11, Daamen discloses wherein the network mapping algorithm considers best scores or percentile scores ([0014]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Daamen. The motivation for combining these references would have been to treat the disease.
Claims 36-38, 45-47, 40-41, and 49-50 are substantially similar to claims 6-8 and 10-11 and hence rejected on similar grounds.
Claims 9, 39, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Cirit in view of Ghiassian in view of Popov, US Patent No. 9,727,893.
Regarding claim 9, Popov discloses using a signature frequency ranking algorithm (claim 14).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Popov. The motivation for combining these references would have been to treat the disease.
Claims 39 and 48 are substantially similar to claim 9 and hence rejected on similar grounds.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Cirit in view of Ghiassian in view of Lee et al., US Patent Application No. 2021/0145879.
Regarding claim 13, Lee discloses a modulator directly acting on one or more targets with or without downstream pleiotropic effects to correct the particular disease state of the disease ([0005]).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the above-noted disclosure of Cirit and Ghiassian with the above-noted disclosure of Lee. The motivation for combining these references would have been to treat the disease.
Response to Arguments
Examiner withdraws 35 U.S.C. 112 (pre-AIA ), second paragraph rejection of claims 24 in view of the amendment/argument.
Applicant's arguments filed dated 9/19/2025 have been fully considered but they are not persuasive due to the following reasons:
With respect to the rejection of claims 1-23 and 34-51 under 35 U.S.C. 101, Applicant states that the claims are now directed to a practical application as claim 1, (as well as independent claims 34 and 43) now recite the practical (and non-abstract) application.
Examiner respectfully disagrees and notes that the additional elements are recited at a high level of generality in that it amounts to simply applying the abstract idea. There is no technical improvements or technical solution to a technical problem. The specification does not identify any technical problem to which a technical solution is sought. In the absence of any technical improvement, the additional elements do not integrate the abstract idea into a practical application. Thus, these arguments are not persuasive.
With respect to the rejection of claims 1-5, 12, 24, 34-45, and 43-44 under 35 U.S.C. 102(a)(2), Applicant’s arguments are moot in view of the new grounds of rejection presented above in this office action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJESH KHATTAR whose telephone number is (571)272-7981. The examiner can normally be reached M-F 8AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Shahid Merchant can be reached at 571-270-1360. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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RAJESH KHATTAR
Primary Examiner
Art Unit 3684
/RAJESH KHATTAR/Primary Examiner, Art Unit 3684