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 5/18/2026 in which claims 1, 34, and 43 have been amended, claim 12 and 24-33 have been canceled. Thus, the claims 1-11, 13-23, and 34-51 are pending in the application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/18/2026 has been entered.
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, 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; and
wherein the drug or the 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 are administered 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]).
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; and
administered to a subject in need thereof in an effective amount to decrease or inhibit 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]-[0007]); and
administered to a subject in need thereof in an effective amount to decrease or inhibit the disease ([0005]-[0007]).
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 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. 101 rejection of claims 1-11, 13-24, and 34-51 in view of the amendment/argument.
Applicant's arguments filed dated 5/18/2026 have been fully considered but they are not persuasive due to the following reasons:
With respect to the rejection of claims 1-5, 23-24, 34-35, 42-44, and 61 under 35 U.S.C. 103, Applicant states that Cirit only teaches applying the drug to the microphysiological systems (MPS) platform, not to a subject.
Examiner respectfully disagrees and notes that the rejection presented above relies on Ghiassian for disclosing applying the drug to a subject. Thus, these arguments are moot.
Conclusion
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
RAJESH KHATTAR
Primary Examiner
Art Unit 3684
/RAJESH KHATTAR/Primary Examiner, Art Unit 3684
Prosecution Insights