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 .
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 merits.
Claim 5 was withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or liking claim.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 were previously 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 04/28/2026 and 06/08/2026 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.
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 17 recites administering a therapeutic chemical, wherein the disease is a disease identified by the method of claim 1 as being associated with the therapeutic chemical.
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).
Furthermore, the additional element of administering a therapeutic chemical is not particular and is merely an intended use of the claimed invention or a field of use limitation, and it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration. See MPEP 2106.04(d)(2) and 2106.05(h).
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
In Step 2A, Prong 1 above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In Step 2B below, any remaining steps and/or elements are therefore in addition to the identified JE(s). Any such additional steps and additional elements are further discussed in Step 2B.
Here in Step 2A, Prong 2, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
At this point in examination, it is not yet the case that any of the Step 2A, Prong 2 considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of 1. an improvement, 2. treatment, 3. a particular machine or 4. a transformation is clear in the record.
For example, regarding the second consideration at MPEP 2106.04(d)(2), the record, does not yet clearly disclose an explanation of a particular treatment or prophylaxis for a disease or medical condition. The claims do not yet clearly result in such particular treatment or prophylaxis (e.g. specification: [0031-0033]).
Therefore, the additionally recited elements amount to generic computer components and field of use, 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 17 recites administering a therapeutic chemical, wherein the disease is a disease identified by the method of claim 1 as being associated with the therapeutic chemical.
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).
Furthermore, the additional element of administering a therapeutic chemical is not particular and is merely an intended use of the claimed invention or a field of use limitation, which the courts have found not to be enough to qualify as "significantly more" when recited in a claim with a judicial exception. See MPEP 2106.05(a).
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.
Response to Arguments
Applicant's arguments filed 04/28/2026 have been fully considered but they are not persuasive. Applicant states:
Applicant's independent Claims 1 and 19 recite a specific set of rules
that improves a technological process (i.e., identifying a disease associated with a therapeutic chemical). Conventional methods of evaluating chemical-disease relations involve evaluation of structural properties of chemical compounds. Applicant's claimed approach can advantageously omit such analysis by accounting for how a chemical interacts with various proteins and how those proteins interact with each other and with associated disease processes through a protein- protein interaction network.
Applicant's claimed approach recites a specific set of rules that does not require knowledge of a specific type of interactions (e.g., activation, inhibition) between
a chemical and its protein targets. See Specification, page 9, paragraph [0055].
This improvement constitutes a technical advancement to the field of identifying a disease associated with a therapeutic chemical.
The above-noted elements recite specific rules for execution. When those rules are carried out (e.g., by a computer processor), the improvements described above are realized.
Such benefits are not provided by prior-art methods. Thus, Applicant's independent Claims 1 and 19 recite specific rules that improve a technological process and, as a result, are not directed to an abstract idea.
Claim 17 recites (emphasis added) "[a] method of treating a subject having a disease, the method comprising administering a therapeutic chemical, wherein the disease is a disease identified by the method of claim 1 as being associated with the therapeutic chemical." As such, Applicant is unable to determine how the Office intended to reject Claim 17 under 35 U.S.C. 101 since Claim 17 recites more than "further information about the protein network and therapeutic chemical." Applicant respectfully submits that the above- noted elements are directed to statutory subject matter.
Applicant remarks are directed to Step 2A Prong Two of 101 analysis, specifically whether the additional elements integrate the recited judicial exception into a practical application of the exception.
With regards to Applicant stating improve a technological process, Examiner submits that an improvement in the abstract idea itself (e.g. identifying a disease associated with a therapeutic chemical) is not an improvement in technology. It is not yet clear what is an improvement to the technology field amounting to a practical application.
Taken as a whole, the instant claims are directed to judicial exception of identifying a disease associated with a therapeutic chemical. It is important to note, the judicial exception alone cannot provide the improvement (See MPEP 2106.04(d) III). The improvement must be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II, below. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. See MPEP § 2106.04(d) (discussing Finjan, Inc. v. Blue Coat Sys., Inc., 879 F.3d 1299, 1303-04, 125 USPQ2d 1282, 1285-87 (Fed. Cir. 2018)). The additional element of a system comprising a processor amounts to simply adding a general-purpose computer or computer components after the fact to an abstract idea and does not integrate a judicial exception into a practical application. See MPEP 2106.05(f). Furthermore, the additionally recited element of administering a therapeutic chemical is not particular and is merely an intended use of the claimed invention or a field of use limitation that does not integrate a judicial exception into a practical application.
With regards to Applicant stating that benefits realized by the claimed invention are not provided by prior-art methods, Examiner submits that that the "‘novelty’ of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claim falls within the § 101 categories of possibly patentable subject matter." Intellectual Ventures I v. Symantec Corp., 838 F.3d 1307, 1315, 120 USPQ2d 1353, 1358 (Fed. Cir. 2016) (quoting Diamond v. Diehr, 450 U.S. at 188–89, 209 USPQ at 9). See also Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151, 120 USPQ2d 1473, 1483 (Fed. Cir. 2016) ("a claim for a new abstract idea is still an abstract idea. The search for a § 101 inventive concept is thus distinct from demonstrating § 102 novelty."). In addition, the search for an inventive concept is different from an obviousness analysis under 35 U.S.C. 103. See, e.g., BASCOM Global Internet v. AT&T Mobility LLC, 827 F.3d 1341, 1350, 119 USPQ2d 1236, 1242 (Fed. Cir. 2016). See MPEP 2106.05 I.
With regards to Applicant referring to claim 17, the 101 rejection is revised to further explain the rejection. As stated in the above rejection, the additionally recites step of administering a therapeutic chemical is not considered as a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2). The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). The additional element of administering a therapeutic chemical is not particular and is merely an intended use of the claimed invention or a field of use limitation, which the courts have found not to be enough to integrate the judicial exception into a “practical application” in Step 2A Prong Two, and does not qualify as "significantly more" in Step 2B, when recited in a claim with a judicial exception.
As such, the rejection of claims under U.S.C. 101 rejection is maintained.
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 generating a distribution of expected reachability values by 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). Guney further discloses examining the enrichment of known drug-disease associations among significantly proximal (that is, zc≦−2) drug-disease pairs and observe a significant increase in the ratio of known drug-disease pairs compared with unknown pairs (odds ratio=5.2, P=2.6×10−27) [0062] (for example, generating a list). Guney further discloses using protein-protein interaction (PPI) network [0088]; 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 that similarity-based methods are powerful in discriminating known drug-disease pairs from unknown drug-disease pairs, they have two main drawbacks: (i) these methods rely on the existing knowledge of drug and disease information, making them prone to overfitting and (ii) they fail to provide insights on the drug mechanism of action. Gene expression profile consistency-based approaches aim to overcome these limitations by investigating correlations between the expression signatures of drug perturbations and the expression profiles in diseases. We use the drug and disease signatures in drug versus disease (DvD) resource and calculate a Kolomgorov-Smirnov statistic-based enrichment score for the 1,980 (95 known, 1,885 unknown) drug-disease pairs that are in the DvD data set. We show that, proximity yields better accuracy than expression correlation-based prediction of drug-disease associations [0057]. Guney further discloses comparing proximity to gene expression-based repurposing. To identify drugs that can potentially account for the gene expression changes induced by diseases, recent studies proposed using correlation of gene expression between the disease state and after treatment with drug. The premise of these studies is to find drugs whose perturbation profiles are anti-correlated with the genes perturbed in the disease such that the treatment with the drug can revert the expression changes in the disease state; We test this hypothesis using Drug versus Disease (DvD) R package to correlate drug and disease gene expression profiles from public microarray repositories. DvD provides the precalculated reference ranked gene lists based on differential expression from disease states in Gene Expression Omnibus… The 200 significantly differentially expressed genes (top and bottom 100 genes in the ranked lists) are used to calculate an enrichment score based on Kolomgorov-Smirnov statistic (i.e., calculateES function in the R package), corresponding to the strength of the anti-correlation of drug and disease profiles. 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]; reading on limitations of applying gene expression information associated with the therapeutic chemical to generate enrichment scores for diseases of the candidate disease list.
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). Guney further discloses identifying the disease pairs that have substantial portion of their genes in common [0138]; reading on limitations of identifying at least one disease associated with the therapeutic chemical based on the determined enrichment scores.
Further regarding claims 1 and 19, 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
media_image1.png
44
207
media_image1.png
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.
Response to Arguments
Applicant's arguments filed 04/28/2026 have been fully considered but they are not persuasive. Applicant states:
Applicant respectfully submits that the cited hypothetical combination does not disclose at least:
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;
applying gene expression information associated with the therapeutic chemical to generate enrichment scores for diseases of the candidate disease list;
and identifying at least one disease associated with the therapeutic chemical based on the determined enrichment scores, as recited, similarly in part, in Applicant's independent Claim 1.
Applicant argues that one or more limitations are not taught by the cited art. As stated in the above rejections, Guney discloses 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 (drug-disease pairs [0021] [0138]); applying gene expression information associated with the therapeutic chemical to generate enrichment scores for diseases of the candidate disease list (using correlation of gene expression between the disease state and after treatment with drug [0130]); and identifying at least one disease associated with the therapeutic chemical based on the determined enrichment scores (identifying the disease pairs that have substantial portion of their genes in common [0138] [0035-0036]). In the same field of research, Chen also provides disease-specific pathway models based on their gene expression profiles and mapping drug-protein interaction (abstract; claim1).
As such, the rejection of instant claims under U.S.C. 103 rejections are maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 GHAZAL SABOUR whose telephone number is (703)756-1289. The examiner can normally be reached M-F 7:30-5:00.
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, 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.
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.
/G.S./ Examiner, Art Unit 1686
/G. STEVEN VANNI/ Primary patents examiner, Art Unit 1686
Prosecution Insights