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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-4, 10-17, 19-22, 28, 29, 31, and 32) in the reply filed on 11/05/2025 is acknowledged.
Claims 5-9 and 23-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/05/2025.
Claim Status
Claims 1-5, 10-11, 13-17, 19-22, 28-29, and 31-32 are pending.
Claims 1-4, 10-11, 13-17, 19-22, 28-29, and 31-32 are examined on the merit.
Claim 5 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or liking claim.
Claims 6-9, 12, 18, 23-27, and 30 are canceled.
Priority
The instant application claims the benefit of a prior-filed application, U.S. Provisional App. No.62/852,800, filed 05/24/2019. In this action, all claims are examined as though they had an effective filing date of 05/24/2019. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/10/2021, 02/16/2022, 09/14/2023, 02/11/2025, and 08/28/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the list of cited references was considered in full by the examiner. A signed copy of the corresponding 1449 form has been included with this Office action.
Drawings
The drawings filed 11/10/2021 are accepted.
Specification
The amendments to the specification filed 11/10/2021 have been accepted.
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 1-4, 10-11, 13-17, 19-22, 28-29, and 31-32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim(s) 1-4, 10-11, and 13-17 being representative) is directed to a method, (claim(s) 19-22, 28-29, and 31-32 being representative) is directed to a system. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claims 1-4, 10-11, 13-17, 19-22, 28-29, and 31-32 recite the following steps which fall under the mathematical concepts, mental processes, and/or certain methods of organizing human activity groupings of abstract ideas:
Claims 1 and 19 recite generating a candidate disease list based on proximities of proteins associated with a plurality of diseases and proteins associated with a therapeutic chemical in a protein-protein interaction network; the limitation generating a list based on proximities involve mathematical formulas and mathematical calculations (as claimed in claims 2-4 and 20-22, as well as specification [0050]), and as such, falls into mathematical concepts groupings of abstract ideas.
Claims 1 and 19 further recite applying gene expression information associated with the therapeutic chemical to generate enrichment scores for diseases of the candidate disease list; the limitation applying information to generate a score is considered a mathematical calculation, as claimed in claims 10-11 and as disclosed in specification [0009-0011] “generating an enrichment score can include… performing a Gene Set Enrichment Analysis” (a computational method of determining gene sets).
Claims 1 and 19 further recite identifying at least one disease associated with the therapeutic chemical based on the determined enrichment scores; the limitation identifying, given the plain meaning of “identifying” can be practically performed in human mind (mental process) since human mind is capable of identifying information based on the result of an analysis.
Claims 2 and 20 recite generating the candidate disease list includes generating a proximity value for a disease and the therapeutic chemical (mathematical calculation/mathematical process).
Claims 3 and 21 recite that the proximity value is determined based on shortest path lengths between nodes representing proteins associated with the disease and nodes representing proteins associated with the therapeutic chemical (mathematical calculation/mathematical process).
Claims 4 and 22 recite the proximity value is a distance metric determined according to a mathematical formula (mathematical formulas/mathematical process).
Claims 10 and 28 recite that generating an enrichment score includes measuring an extent of gene expression perturbation by the therapeutic chemical for a disease (mathematical calculation/mathematical process).
Claims 11 and 29 recite that measuring the extent of gene expression perturbation includes performing a Gene Set Enrichment Analysis (mathematical calculation/mathematical process).
Claims 13 and 31 recite ranking the diseases of the candidate disease list based on the determined proximity and the determined enrichment scores (mathematical relationship/mathematical process).
Claims 14-17 and 32 provide further information about the protein network and therapeutic chemical.
The identified claims recite a law of nature, a natural phenomenon (product of nature) and/or fall into one of the groups of abstract ideas of mathematical concepts, mental processes, and/or certain methods of organizing human activity for the reasons set forth above. See MPEP 2106.04 (a)(2) III and MPEP 2106.04 (b) I. Therefore, claims are directed to one or more judicial exception(s) and require further analysis in Prong Two. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
The additional elements of claims 1-4, 10-11, 13-17, 19-22, 28-29, and 31-32 include the following.
Claim 19 recites a system comprising a processor.
The additional elements of a system comprising a processor is generic computer components and/or processes. There are no limitations that indicate that the processor, input module, processing module, or output module in the computer-implemented system require anything other than generic computing systems. The courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general-purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application. See MPEP 2106.05(f).
Therefore, the additionally recited elements amount to generic computer components, as such, the claims as a whole do no integrate the abstract idea into practical application. See MPEP 2106.05(g). Thus, claims 1-4, 10-11, 13-17, 19-22, 28-29, and 31-32 are directed to an abstract idea. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. An inventive concept cannot be furnished by an abstract idea itself. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
The additional elements of claims 1-4, 10-11, 13-17, 19-22, 28-29, and 31-32 include the following.
Claim 19 recites a system comprising a processor.
The additional elements of a system comprising a processor is conventional computer components and/or processes. The courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general-purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TU Communications LLC v. AV Auto, LLC, 823 F.3d 607,613,118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit).
Therefore, the additional element is not sufficient to amount to significantly more than the judicial exception.
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-4, 13-15, 17, 19-22, and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Guney et al. (US20170270254A1) in view of Chen et al. (US20130144887A1).
Regarding claims 1 and 19, Guney discloses a method of determining whether a drug is therapeutically beneficial to a disease (claim 4, [0004] [0033] [0036]); reading on limitations of a method of identifying a disease associated with a therapeutic chemical.
Guney further discloses determining a reachability value between a first node group (including representations of drug targets) and a second node group (including representations of disease proteins) [0034-0036] (FIGs. 1, 3, 14-17); reading on limitations of generating a candidate disease list based on proximities of proteins associated with a plurality of diseases and proteins associated with a therapeutic chemical in a protein-protein interaction network.
Guney further discloses identifying whether a drug is therapeutically beneficial to or is effective for palliative treatment of a disease [0035] and determining a new application for a drug corresponding to the first node group for a disease corresponding to the second node group [0036] (FIG. 3); reading on limitations of identifying at least one disease associated with the therapeutic chemical based on the determined enrichment scores.
Guney further discloses that their proximity method provides an alternative to the drug similarity and gene expression based repurposing approaches that can offer an interactome-based explanation towards the drug's effect on a disease. Guney further discloses that the combination of proximity and gene expression-based repurposing could offer increased predictive power, given the orthogonal nature of the information the two classes of methods use [0057]. Guney further compares proximity to gene expression-based repurposing and discloses using drug and disease gene expression profiles to calculate an enrichment score based on Kolomgorov-Smirnov statistic (i.e., calculate ES function in the R package), corresponding to the strength of the anti-correlation of drug and disease profiles. Guney further discloses that DvD had information for 72 drugs and 14 diseases in our data set covering 95 out of 402 known drug-disease pairs and 1,885 out of 18,162 unknown pairs [0130].
Further regarding claims 1 and 19, Guney does not expressly disclose applying gene expression information associated with the therapeutic chemical to generate enrichment scores for diseases of the candidate disease list.
Chen discloses an integrative pathway modeling approach and ranking/evaluating algorithms based on disease-specific pathway models can predict drug efficacy for patients based on their gene expression profiles. Chen further discloses determining compounds for the treatment of a particular disease, said method comprising: generating a list of proteins related to the particular disease; selecting a plurality of drug pathways from a pathway database based on the list of proteins; annotating each of the plurality of drug pathways; mapping each drug-protein interaction on each of the plurality of drug pathways including identifying effector proteins; translating the mapped plurality of drug pathways into a weighted network; and calculating a ranking of the drugs associated with the plurality of drug pathways based on the effector proteins in each of the plurality of drug pathways and providing a ranking of drugs associated with the pathways for treatment of the particular disease (claim 1). Chen further discloses that the mapping step includes mapping a expression profile onto identified effector proteins (claim 2).
Regarding claims 2 and 20, Guney discloses proximity between the first node group and the second node group is determined based on (i) the reachability value between the first node group and the second node group, (ii) the mean of the distribution of expected reachability values, and (iii) the standard deviation of the distribution of expected reachability values [0036] FIG. 3; reading on limitations of generating the candidate disease list includes generating a proximity value for a disease and the therapeutic chemical.
Regarding claims 3 and 21, Guney discloses that the reachability value is determined by averaging a shortest path length from each node in the first node group to a closest node in the second node group [0036] FIG. 3; reading on limitations of the proximity value is determined based on shortest path lengths between nodes representing proteins associated with the disease and nodes representing proteins associated with the therapeutic chemical.
Regarding claims 4 and 22, Guney discloses use of closest measure, dc, representing the average shortest path length between the drug's targets and the nearest disease protein [0049][0091], formula (1); reading on limitations of the proximity value is a distance metric dc(S,T) determined according to:
PNG
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44
207
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Greyscale
where Sis a set of proteins associated with the disease, Tis a set of proteins associated with the therapeutic chemical, s is a node representing a protein in set S, t is a node representing a protein in set T, and d (s,t) is a shortest path length between nodes .s and t in the protein network.
Regarding claims 13 and 31 Guney discloses ranking all the pathways with respect to their proximity to a given drug [0104]. Chen discloses calculating a ranking of the drugs associated with the plurality of drug pathways based on the effector proteins in each of the plurality of drug pathways and providing a ranking of drugs associated with the pathways for treatment of the particular disease (claim 1). Chen further discloses pathway/network model-based drug ranking algorithm is developed to evaluate the pharmacological effects of drugs on the target proteins [0056]; reading on limitations of ranking the diseases of the candidate disease list based on the determined proximity and the determined enrichment scores.
Regarding claims 14 and 32, Guney discloses that the protein-protein interaction network is human interactome [0134]; reading on limitations of the protein- protein interaction network is a human interactome.
Regarding claims 15 and 17, Guney discloses that in order to demonstrate the utility of the relative proximity, FIG. 8b shows the shortest paths between drug targets and disease proteins for two known drug-disease associations: Gliclazide-type 2 diabetes (T2D) and daunorubicin-acute myeloid leukemia (AML). Gliclazide binds to ATP-binding cassette sub-family C member 8 (ABCC8) and vascular endothelial growth factor A and stimulates pancreatic beta-islet cells to release insulin. ABCC8 is a known T2D gene (MIM:600509) and there is at least one protein associated with T2D within two steps of vascular endothelial growth factor A's neighborhood corresponding to an average distance of dc=1.0 between the drug and the disease using the closest measure. The relative proximity between the drug and the disease is zc=−3.3, suggesting that the targets of gliclazide are closer to the T2D proteins than expected by chance (see FIG. 8c ). Similarly, the relative proximity of daunorubicin, an anthracycline aminoglycoside inhibiting the DNA topoisomerase II (TOP2A and TOP2B), to AML is zc=−1.6, offering network-based support for daunorubicin's therapeutic effect in AML [0050]; reading on limitations of proteins associated with a therapeutic chemical are proteins to which the therapeutic chemical binds and administering a therapeutic chemical, wherein the disease is a disease identified by the method of claim 1 as being associated with the therapeutic chemical.
In KSR Int 'l v. Teleflex, the Supreme Court, in rejecting the rigid application of the teaching, suggestion, and motivation test by the Federal Circuit, indicated that “The principles underlying [earlier] cases are instructive when the question is whether a patent claiming the combination of elements of prior art is obvious. When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR Int'l v. Teleflex lnc., 127 S. Ct. 1727, 1740 (2007).
Applying the KSR standard to Guney and Chen, examiner concludes that the combination of Guney and Chen represents the use of known techniques to improve similar methods. Both Guney and Dean are directed to therapeutic chemicals and disease interactions. Guney only disclosed generating a candidate disease list based on proximities of proteins and identifying disease associated with the therapeutic chemical. Guney disclosed that applying gene expression information associated with the therapeutic chemical to generate enrichment scores in known in the art and used it while comparing his proximity method to the gene expression-based repurposing. In the same field of research, Chen predicted drug efficacy for patients based on their gene expression profiles. Combining the proximity method of Guney with gene expression analysis of Chen would have allowed for integrating functional activity with molecular connectivity. One ordinary skilled in the art before he effective filing data of the claimed invention would have had a reasonable expectation of success at combining the method of Guney and Chen. This combination would have been expected to have provided a more accurate identification of a disease associated with a therapeutic chemical. Therefore, the invention would have been prima facie obvious to one of skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Claims 10-11 and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Guney et al. (US20170270254A1) in view of Chen et al. (US20130144887A1)as applied to claims 1-4, 13-15, 17, 19-22, and 31-32 above, and further in view of Dean et al. (Application of Gene Set Enrichment Analysis for Identification of Chemically Induced, Biologically Relevant Transcriptomic Networks and Potential Utilization in Human Health Risk Assessment, January 25, 2017, TOXICOLOGICAL SCIENCES, 157(1), 2017, 85–99).
Claims 10-11 and 28-29 depend on claims 1, 2, 7, and 19. Limitations of said claims has been taught in the above rejections.
Regarding claims 10-11 and 28-29, Chen discloses that in order to detect a specific state of a condition or disease to facilitates selection of treatments Gene Set Enrichment Analysis (GSEA) and similar methods can be employed [0026].
Dean discloses transcriptomics and the application of gene expression analysis to characterize biological responses to chemical exposures. Dean further discloses employing GSEA to identify significantly enriched transcriptional events following repeated-dose chemical exposure and evaluated the manner in which dose and time affects the enrichment of various biologically relevant gene groups/signaling pathways for potential application in qualitative and quantitative human health risk assessments.
Dean further discloses Median transcriptional BMD values were calculated for the most sensitive enriched pathway as well as the overall median BMD value for key gene members of significantly enriched pathways, and both were observed to be good estimates of the most sensitive apical endpoint BMD value (abstract).
Dean discloses employing gene set enrichment analysis (GSEA) to evaluate tissue-specific, dose-response gene expression data (abstract); reading on limitations of generating an enrichment score includes measuring an extent of gene expression perturbation by the therapeutic chemical for a disease includes performing a Gene Set Enrichment Analysis.
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 Guney and Chen to have used the known gene expression information/gene set enrichment analysis of Dean to better characterize biological responses to chemical exposure. One ordinary skilled in the art could have applies the known “improvement” of Dean in the same way to the base method of Guney and Chen and the results would have been predictable to one ordinary skilled in the art.
Claims 10-11 and 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Guney et al. (US20170270254A1) in view of Chen et al. (US20130144887A1), as applied to claims 1-4, 13-15, 17, 19-22, and 31-32 above, and further in view of Lacroix et al. (A computationally driven analysis of the polyphenol-protein interactome, published: 02 February 2018, Scientific Reports volume 8, Article number: 2232, pages 1-13) ("previously cited on the 02/16/2022 IDS form").
Claim 16 depends on claim 1. Limitations of claim 1has been taught in the above rejections.
Regarding claim 16, Guney discloses gliclazide binding to ATP-binding cassette sub-family C member 8 (ABCC8) and vascular endothelial growth factor A.
Further regarding claim 16, Guney and Dean do not disclose that the therapeutic chemical is a polyphenol and the proteins associated with the therapeutic chemical are binding targets of the polyphenol.
Lacroix discloses identifying proteins that interact with or metabolize polyphenols, mapping these proteins to pathways and networks, and annotating functions enriched within the resulting polyphenol-protein interactome. Lacroix further discloses identifying a broad coverage of significant pathways of low specificity to particular polyphenol (sub)classes using Pathway enrichment analysis using the KEGG repository.
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 Guney and Chen to have used the known therapeutic chemical of Lacroix (Abstract) based on the finding that at the time of the invention, there had been a recognized need in the art to map the polyphenol-protein interactome given its wide range of effects on human health and diseases. One ordinary skilled in the art would have had reason to try polyphenol and its associated proteins in method of Guney and Chen with the reasonable expectation of success. Therefore, the method is not of innovation but of ordinary skill and common sense.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GHAZAL SABOUR whose telephone number is (703)756-1289. The examiner can normally be reached M-F 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs can be reached at (571) 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.S./ Examiner, Art Unit 1686
/LARRY D RIGGS II/ Supervisory Patent Examiner, Art Unit 1686