DETAILED ACTION
In application filed on 06/23/2023, Claims 14-33 are pending. The claim set submitted on 07/31/2026 is considered because this is the most recent claim set. Claims 17-21 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/07/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group 1 (Claims 17-21) in the reply filed on 07/31/2026 is acknowledged.
Regarding the potential examination of Claim 22-33 (previously included with Claim 14- Group I) in conjunction with Claims 17-21, Examiner will consider a Rejoinder in pursuant to the procedures set forth in MPEP § 821.04, on Claims 22-23 with Claim 17, when allowable subject matter in Claim 17 is identified.
Claims 17-21 are considered in the current office action.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 17 is rejected under 35 U.S.C. 102 (a) (2) as being anticipated by Sances et al. (US20210130774A1).
Regarding Claim 17, Sances teaches a method comprising:
obtaining a microphysiological system (MPS) (See Abstract… a microphysiological system for models of disease.) comprising brain tissue (See Para 00077… human brain tissues) and blood brain barrier (BBB) tissue (See Para 0009… the blood brain barrier (BBB); See Para 0139…with cortical and endothelial cells to create a BBB allows for the innovative examination of how serum from FTLD-TDP patients may affect neuronal phenotypes in this human forebrain model; Examiner submits that tissues are made up of cells), wherein at least one of the brain tissue (See Para 0007… living human brain tissues; See Para 0008… The PD-Chip is a culture system that utilizes iPSC-derived tissues to create a “brain-on-chip” model) and the BBB tissue (See Para 0009… the blood brain barrier (BBB); See Para 0139…with cortical and endothelial cells to create a BBB allows for the innovative examination of how serum from FTLD-TDP patients may affect neuronal phenotypes in this human forebrain model; Examiner submits that tissues are made up of cells) comprises a disease (See Para 0008… The PD-Chip is a culture system that utilizes iPSC-derived tissues to create a “brain-on-chip” model that represents specifically the part of the brain that degenerates in Parkinson's disease; See Para 0077…a Parkinson's Disease (PD), PD-Chip is used to model PD in a perfusable system that enables a full array of cellular assays on living human brain tissues);
treating the brain tissue and the BBB tissue with a drug or a combination of drugs (See Para 0009…The fourth is the combination of an active blood brain barrier with the neural tissue to allow administration of drugs either to the brain side or the blood side, which would simulate the ability of the compound to cross the blood brain barrier.) to determine a phenotypic effect and a transcriptomic effect (See Abstract…A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue) of the drug (See Para 0129…Final candidates are validated using the full range of biomarkers to determine how well the phenotypic changes are reversed by each drug, in addition to metabolomic changes; See Para 0133…The primary outcome of this project is the establishment of reproducible disease specific phenotypes of both sporadic ALS and PD that will then be used as biomarkers to screen for novel phenotype-reducing drugs either to the brain side or the blood side, which would simulate the ability of the compound to cross the blood brain barrier.).
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.
Claims 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Sances et al. (US20210130774A1) in view of Fouladiha et al. ("Biomedical applications of cell-and tissue-specific metabolic network models." Journal of biomedical informatics 68 (2017): 35-49.)
Regarding Claim 19, Sances teaches the one or more therapeutic targets (See Para 0111… If needed due to low abundance of target proteins, the Inventors can concentrate the effluent or combine samples harvested from multiple MPS devices, thereby teaching “one or more therapeutic targets”).
Sances does not teach determining one or more therapeutic targets for treatment of a neurodegenerative disease based on context-specific genome-scale metabolic model (GEM).
In the analogous art of biomedical applications of cell- and tissue-specific metabolic network models, Fouladiha teaches determining one or more therapeutic targets for treatment of a neurodegenerative disease (See Page 38… The authors also proposed novel sets of biomarkers and drug targets for AD.) based on context-specific genome-scale metabolic model (GEM) (See Page 38… Another possible application of human GEMs is the mapping of omics data on the network [45], in order to understand the important activated or inactivated parts of cell metabolism.).
Fouladiha further teaches that Constraint-based analysis of both cell- and tissue specific metabolic network models have been proven to be useful in biomedical research, e.g., for predicting biomarkers and drug targets or studying metabolic pathways (Fig. 2) (See Page 39).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Sances to include “determining one or more therapeutic targets for treatment of a neurodegenerative disease based on context-specific genome-scale metabolic model (GEM)”, as taught by Fouladiha for the benefit of predicting biomarkers and drug targets or studying metabolic pathways (Fig. 2) (Fouladiha, See Page 39), allowing for the providing a method of how these models have been used in analyzing metabolic capabilities of different cells and tissues, in identifying disease-related metabolic pathways and biomarkers, and in understanding the human-microbe interaction (Fouladiha, Abstract).
Regarding Claim 21, the method of claim 19 is obvious over Sances in view of Fouladiha.
Sances teaches that the one or more therapeutic targets comprise one or more of an mRNA, a protein, and a metabolite (See Para 0111… If needed due to low abundance of target proteins, the Inventors can concentrate the effluent or combine samples harvested from multiple MPS devices, thereby teaching “target protein”).
Allowable Subject Matter
Claims 18 and 20 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding Claim 18, Sances teaches further comprising determining one or more phenotypic markers related to the disease (See Para 0162…the serum chosen will be from the FTLD-TDP patient (either C9orf72 or GRN) in which the Inventors observe the greatest enhancement or expression of disease phenotypes);
perturbing the brain tissue (See Para 00077… human brain tissues) and the BBB tissue (See Para 0009… the blood brain barrier (BBB); See Para 0139…with cortical and endothelial cells to create a BBB allows for the innovative examination of how serum from FTLD-TDP patients may affect neuronal phenotypes in this human forebrain model; Examiner submits that tissues are made up of cells) using the drug (See Para 0133… biomarkers to screen for novel phenotype-reducing drugs either to the brain side or the blood side, which would simulate the ability of the compound to cross the blood brain barrier);
optimizing (See Para 0007… determining blood brain barrier permeability, thereby teaching “optimizing”) at least one kinetic parameter (‘blood brain barrier permeability’) representing the brain tissue or the BBB tissue (See Para 0007…it can be used for the screening for novel drugs with the added benefit of determining blood brain barrier permeability; See Para 0041…).
Sances does not teach “relating the perturbation to the phenotypic effect and the transcriptomic effect based on the optimization”.
In the analogous art of biomedical applications of cell- and tissue-specific metabolic network models, Fouladiha teaches “using the same metabolic network model, showed that SNPs (Single-Nucleotide Polymorphisms) which are related to reactions with correlated fluxes are linked to the same phenotypes. The mentioned network was also helpful in identifying critical genes and reactions in hypoxia tolerance in the human heart (Page 40)
Further, Fouladiha teaches “Cancer advancement process in the body could be visualized through its effects on metabolic pathways. For example, Jerby et al. defined a score for each metabolic pathway, in order to predict metabolic phenotype, using CBM to find the optimum fit between transcriptome data and flux distribution of a human metabolic model” (Page 42).
However, the combination of Sances and Fouladiha neither teaches nor suggests “relating the perturbation to the phenotypic effect and the transcriptomic effect based on the optimization” (as claimed in Claim 18).
Regarding Claim 20, the method of claim 19 is obvious over Sances in view of Fouladiha (see Claim 19 rejection).
However, Neither Sances nor Fouladiha in combination or alone teaches “generating the GEM by: determining a tissue type represented in the MPS; preserving a gene-protein-reaction association based on tissue-specificity data; and performing a metabolic simulation including the gene-protein-reaction association to validate the GEM” 9 (as claimed in Claim 20).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
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