CTNF 17/978,305 CTNF 100270 DETAILED ACTION Notice of AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. 07-06 AIA 15-10-15 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. Status of the Claims Claims 1-21 are pending. Claims 1, 6-11, and 16-19, and 21 are objected to. Claims 1-21 are rejected. Priority This US Application 17/978,305 (11/01/2022) and claims no priority herein, as reflected in the filing receipt mailed on 03/03/2023. The claims to the benefit of priority are acknowledged; and the effective filing date of claims 1-21 is 11/01/2022 . Information Disclosure Statement The information disclosure statements (IDS) submitted on 11/01/22 was considered. Claim objections Claims 1, 6-11, and 16-19, and 21 are objected to because of the following informalities related to inconsistent claim language. Appropriate correction is required. In claim 1 , the recited " each of the similarity criteria" (i.e. lines 12 and 26) should read " each of the similarity criteria of the plurality of similarity criteria". Claim 7 repeats the issue (i.e. line 20). Claim 8 repeats the issue (i.e. line 23). Claim 10 repeats the issue (i.e. line 12). Claim 11 repeats the issue above. (i.e. lines 20 and last line). Claim 17 repeats the issue (i.e. line 5). Claim 18 repeats the issue (i.e. line 8). Claim 19 repeats the issue (i.e. line 17). Claim 21 repeats the issue (i.e. lines 7 and 22). In claim 1 , the recited "plurality of secondary target protein " (i.e. lines 1, 9, and 15) should read "plurality of secondary target proteins ". Claims 6 and 16 repeat the issue above (i.e. last line). Claim 11 repeats the issue above (i.e. lines 1, 17, and 23). Claim 21 repeats the issue above (i.e. lines 1, 4, and 10). In claim 1 , the recited "one or more relevant secondary target protein " (i.e. lines 20 and 25) should read "one or more relevant secondary target proteins ." Claim 11 repeats the issue above (i.e. line 4 - "processing" step - and line 6 - second "determining" step). Claim 21 repeats the issue above (i.e. lines 16 and 19). In claim 7 , the recited “multi-criteria decision-making matrix” should read “ a multi-criteria decision-making matrix.” Claim 17 repeats the issue above. In claim 9 , the recited " connected said plurality of nodes" (i.e. line 4) should read " connected to said plurality of nodes". In claim 9 , the recited “each of the nodes" (i.e. line 5) should read “each of the nodes of the plurality of nodes.” In claim 9 , the recited the commas on lines 6 and 8 should be deleted. Claim Rejections - 35 USC § 112(b) The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. Claims 1-21 are rejected under 35 U.S.C. 112(b)as being indefinite for failing to particularly point out and distinctly claim the subject matter the invention. Dependent claims are rejected similarly, unless otherwise noted below. The following issues cause the respective claims to be rejected under 112(b) as indefinite: Claim 1 , lines 19-23, recites “process the plurality of clusters to identify one or more relevant clusters, wherein the one or more relevant clusters include the primary target protein and one or more relevant secondary target protein…”. However, there is no requirement that the primary target protein is included in the multi-relational directed network, as lines 14-15 recite “build a multi-relational directed network from the determined plurality of secondary target protein”. It is therefore not clear whether the claim should recite that the multi-relational directed network is built from the primary and secondary target proteins, or if the network is comprised only of the secondary target proteins such that it is not clear that a relevant cluster would exist. For compact examination, it is assumed that the primary target protein is included in the network when it is built. The rejection may be overcome by clarifying the metes and bounds of the network. Claims 11 and 21 repeat the issue above. In claim 5 , the term “the data that describes the primary target protein” lacks sufficient antecedent basis because there is no previous recitation of data that describes the primary target protein. It is noted that claim 1 recites “information associated with a primary target protein”. It is therefore not clear if claim 5 intended to refer to that information, which is assumed for compact examination, or some new type of data. The rejection may be overcome by clarifying the antecedent basis of the limitation. Claim 15 repeats the issue above. In claim 4 , the recited "the set of similarity criteria" lacks sufficient antecedent basis because there is no previous recitation of a set of similarity criteria in claim 1. Claims 10 and 20 repeat the issue above with " the edges." Claims 13-20 recite "The system of claim," ultimately depending on claim 11, which is directed to a method claim and not a system claim, rendering the claims indefinite. To overcome this rejection, the claims could be amended to "the method of". For compact prosecution, claims 13-20 are being interpreted as method claims. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-21 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas, natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). 101 background MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials. Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)? Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e ., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))? Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))? Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)? Analysis of instant claims Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)? The instant claims are directed to a system ( claims 1-10 and 13-20 ), a method ( claims 11-12 ), and a CRM ( claim 21 ); each of which falls within one of the categories of statutory subject matter. [Step 1: claims 1-21: Yes] Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))? Background With respect to Step 2A, Prong One , the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as: • mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations) (MPEP 2106.04(a)(2)(I)); • certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or • mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)). Analysis of instant claims Mathematical concepts recited in instant claims 1, 7-11, and 17-21 include the terms: • "build a multi-relational directed network from the determined plurality of secondary target protein" ( claims 1, 11, and 21 ); • "matrix analysis" ( claims 1, 11, and 21 ) • "analysis of multi-criteria decision-making matrix" ( claims 7 and 17 ); • "calculate/calculating priority scores associated with each of the similarity criteria" ( claims 8 and 18 ); • "calculate/calculating direct scores and/or indirect scores of the relevant secondary target protein" ( claims 10 and 20 ); • "perform a clustering operation on the multi-relational directed network via a clustering algorithm" ( claims 1, 11, and 21 ); • "process the plurality of clusters to identify one or more relevant clusters" ( claims 1, 11, and 21 ); and • "assign weights to each of the similarity criteria" ( claims 1, 7, 11, 17, and 21 ). Said terms are being identified as mathematical concepts. The claims in this application are given their broadest reasonable interpretation (BRI) using the plain meaning of the claim language in light of the specification as it would be understood by one having ordinary skill in the art. In this instant disclosure, [0017] describes the use of a clustering algorithm to build the multi- relational directed network; which indicates the use of math. In this instant disclosure, [0079] describes the claimed network using processor to perform clustering operations using mathematical algorithms; which indicates the use of math. In this instant disclosure, [0063] describes the use of matrices for the mathematical calculations of the claimed scores; which indicates the use of math. Thus, the recited terms correspond to verbal equivalents of mathematical concepts because they constitute actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). MPEP 2106.04(a)(2) pertains Mental processes , defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include: • "build a multi-relational directed network from the determined plurality of secondary target protein" ( claims 1, 11, and 21 ); • "matrix analysis" ( claims 1, 11, and 21 ) • "analysis of multi-criteria decision-making matrix" ( claims 7 and 17 ); • "calculate/calculating priority scores associated with each of the similarity criteria" ( claims 8 and 18 ); • "calculate/calculating direct scores and/or indirect scores of the relevant secondary target protein" ( claims 10 and 20 ); • "perform a clustering operation on the multi-relational directed network via a clustering algorithm" ( claims 1, 11, and 21 ); • "process the plurality of clusters to identify one or more relevant clusters" ( claims 1, 11, and 21 ); • "assign weights to each of the similarity criteria" ( claims 1, 7, 11, 17, and 21 ); • "determine a priority sequence of the … protein" ( claims 1, 11, and 21 ); • "validate/validating the received information associated with the primary target protein" ( claims 2 and 12 ) Under the BRI, the recited limitations are mental processes because a human mind is sufficiently capable of performing the mathematical calculations, validating information received and determining a protein sequence with a pen and paper. Dependent claims 4, 6, 14, and 16 recite further details about the "matrix" analysis. Dependent claims 7 and 17 recite further details about the "weights" assigned in the algorithm. Dependent claims 8, 10, 18, and 20 recite further details about the "priority scores" calculated. Dependent claims 9 and 19 recite further details about the "multi-relational directed network" structure. Dependent claims 3 and 13 recite further details about validating the information received. These dependent claims do not recite any additional non-abstract elements; all recite further aspects of the information being analyzed or the manner in which that analysis is performed. Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. The instant claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: claims 1-21: Yes] Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))? Background 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). Analysis of instant claims Instant claims 1-2, 7-8, 10-12, and 21 recite additional elements that are not abstract ideas: • "receive/receiving information associated with a primary target protein" ( claim, 1, 11, and 21 ); • computer-implemented ( claims 11-12 ); • "processor" ( claims 1-2, 7-8, and 10 ); and • "non-transitory computer readable storage medium, containing program instructions for execution on a computer system" ( claim 21 ). Dependent claims 5 and 15 recite further details about the receiving step. Considerations under Step 2A, Prong Two The recited limitations in claims 1-2, 7-8, 10-12, and 21 are interpreted as requiring the use of a computer. The use of a computer is broadly interpreted and not actually described in the claims or specification. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions or instructions to implement on a generic computer. Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Claims reciting "receive/receiving" read on receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321 - MPEP 2106.05(a) pertains; which constitutes just necessary data gathering and therefore correspond to insignificant extra-solution activity. The recited claims read on data gathering activities or the type of data being gathered; not amounting to a practical application. The type of data doesn’t change that it is mere data gathering or conventional computer receiving means. Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)). None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information. In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs). In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements . Additional elements are further discussed in Step 2B below. Here in Step 2A, Prong Two, 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 Two 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 first consideration at MPEP 2106.04(d)(1) , the record, including for example the specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field. The claims do not yet clearly result in such an improvement. [Step 2A Prong Two: claims 1-21: No] Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)? According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s). The instant claims recite a computer or computer functions, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions; which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). The computer-related elements or the general purpose computer and the multi-relational directed network do not rise to the level of significantly more than the judicial exception. The claims state a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (Alice Corp., 573 U.S. at225-26, 110 USPQ2d at 1984; see MPEP 2106.05(A)). Further, the courts have found that receiving data steps are well-understood, routine, and conventional functions of a computer when claimed in a generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versa ta Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(Il)(i)). When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h). [Step 2B: claims 1-21: No] Conclusion: Instant claims are directed to non-statutory subject matter For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 - 07-08-aia AIA (a)(l) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (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. 07-15 AIA Claim s 1-2, 4, 7-12, 14, and 17-21 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Li ("Identification of protein complexes from multi-relationship protein interaction networks." Human Genomics 10(2):17 (2016)), as cited on the attached Form PTO-892 . Li discloses a multi-relationship protein interaction network by integrating protein-protein interaction network topology with gene ontology annotation information. (pg. 61 para. 1). Bullet points indicate the teachings of the instant features over the prior art. Instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims. Claim 1 recites: wherein the system comprises: a database arrangement; and a processor communicably coupled via a data communication network to the database arrangement, wherein the processor is configured to: receive information associated with a primary target protein; determine the plurality of secondary target protein similar to the primary target protein based on a plurality of similarity criteria • Li teaches an algorithm (i.e. computer implemented method ) that predicts protein complexes based on multi-relationship protein interaction network (i.e. processor communicably coupled via a data communication network ) (pg. 61 para. 2) by using a gene ontology database organized by categories (i.e. database arrangement ) namely molecular function, biological process, and cellular component (i.e. similarity criteria ) (pg. 63 col. 1 para. 2); wherein a pair of proteins (i.e. primary and secondary protein targets) may be connected by more than one type of links (pg. 62 col 2 para. 4). perform a matrix analysis to assign weights to each of the similarity criteria from the plurality of similarity criteria • Li teaches an algorithms that output a weighted multi-relationship protein interaction network (pg. 64 Fig. 2); wherein ECC matrices are used to calculate the weight of protein pairs (pg. 63 col. 2 para. 1). build a multi-relational directed network from the determined plurality of secondary target protein; • Li teaches that protein interactions in the network are weighed according to the number of common functions (i.e. multi-relational directed network ); wherein for a pair of proteins v i and v j (i.e. secondary protein target ), BP i and BP j are sets of biological processes of vi and vj, respectively and W_BP v i and v j is the strength of sharing biological processes (pg. 63 col. 2 para. 2). perform a clustering operation on the multi-relational directed network via a clustering algorithm, to group the multi-relational directed network into a plurality of clusters; process the plurality of clusters to identify one or more relevant clusters, wherein the one or more relevant clusters include the primary target protein and one or more relevant secondary target protein connected directly and/or indirectly with the primary target protein • Li teaches the identification of protein complexes (i.e. primary and secondary protein targets identification) through mining density subgraphs (i.e. the step of mining density subgraphs reads on a clustering operation because it executes the same function of identifying areas of higher density and separating those areas into subsets) from four networks (pg. 65 col. 1 para. 2) namely PPI network, biological processes (BP) network, molecular function (MF) network and cellular component (CC) network; wherein the decomposition of a multi-relationship protein interaction network depicted in density subgraphs (i.e. identify one or more relevant clusters ) (pg. 65 Fig. 3). determine a priority sequence of the one or more relevant secondary target protein connected to the primary target protein based on the assigned weights to each of the similarity criteria • Li teaches that the algorithm starts from a randomly chosen protein vertex (i.e. primary protein target ) and add protein vertices via a greedy procedure to form a candidate complex (i.e. complex comprising one or more secondary protein targets ) (pg. 65 col. 2 para. 2); wherein the growth process is repeated from all vertices to form non-redundant complex sets (pg. 66 col. 1 para. 1); wherein the algorithm identifies complexes according to the neighbors of all proteins in the network (pg. 66 col. 1 para. 2); wherein a new neighbor node is maintained if the weighed density of the candidate complex is more than a threshold (i.e. determining the priority sequence based on assigned weighs ) and removed if less than a threshold (pg. 66 col. 1 para. 2). Claim 2 recites: wherein the processor is configured to validate the received information associated with the primary target protein based on authentication and abstraction of data using one or more ontologies, wherein the data relates to the information associated with the primary target protein • Li teaches constructing a multi-relationship protein interaction network by integrating PPI network topology with gene ontology annotation information (pg. 62 col. 2 para. 1); wherein the gene ontology annotation helps increase of the number of protein complexes correctly matched and overcome issues with false negatives and false positive (i.e. authentication and abstraction of data using one or more ontologies ) (pg. 63 col. 1 para. 1). Claim 4 recites: wherein the set of similarity criteria comprises at least one of protein-protein interaction, molecular function similarity, protein sequence similarity, and disease target similarity • Li teaches an algorithm that predicts protein complexes based on multi-relationship protein interaction network (i.e. protein-protein integration ) (pg. 61 para. 2) . Claim 7 recites: wherein the processor is configured to assign weights to each of the similarity criteria based on an analysis of multi-criteria decision-making matrix • Li teaches an algorithm that outputs a weighted multi-relationship protein interaction network (i.e. a type of graph) (pg. 64 Fig. 2); wherein ECC matrices are used to calculate the weight of protein pairs (pg. 63 col. 2 para. 1) to apply weighting and filtering steps and weight PPI interactions based on the analysis of topological features of PPI networks and according to the number of common functions (including BP, MF, and CC) between two proteins (i.e. multi-criteria decision-making matrix ) (pg. 63 col. 2 para. 1). Claim 8 recites: wherein the processor is configured to calculate priority scores associated with each of the similarity criteria for calculating the weights to be assigned to each of the similarity criteria, wherein the priority scores determine the importance of a similarity criteria with respect to other similarity criteria • Li teaches that for a pair of proteins v i and v j , BP i and BP j are sets of biological processes of vi and vj, respectively and W_BP v i and v j is the score for the strength of sharing biological processes (pg. 63 col. 2 para. 2); wherein in a similar way, W_MF (v i , v j ) and W_CC (v i , v j ) denote the scores for the strengths of sharing molecular functions and cellular components of vi and vj, respectively (i.e. priority scores associated with each of the similarity criteria for calculating the weights to be assigned to each of the similarity criteria ) (pg. 63 col. 2 para. 3); Claim 9 recites: wherein the multi-relational directed network defines a plurality of nodes and one or more edges connected said plurality of nodes, wherein each of the nodes in the multi-relational directed network, corresponds to the plurality of secondary target proteins, further wherein the one or more edges in the multi-relational directed network, corresponds to each of the similarity criteria and the weights assigned therewith • Li teaches a multi-relationship protein interaction network where vertices are proteins and edges are PPIs (pg. 61 col. 2 para. 2) and more than one connection between two nodes and each of them has its own property (pg. 62 col. 2 para. 2); wherein a typical multi-relationship network shows proteins A and B connected by physical interaction, co-expression, and co-annotation between nodes (pg. 63 Fig. 1); wherein weighting and filtering steps are applied to weight and filter PPI interactions based on the analysis of topological features of PPI networks and according to the number of common functions (including BP, MF, and CC) between two proteins (i.e. similarity criteria and the weights assigned) (pg. 63 col. 2 para. 1). Claim 10 recites: wherein the processor is configured to calculate direct scores and/or indirect scores of the relevant secondary target protein based on the weights of the similarity criteria assigned to each of the edges defined in the multi-relational directed network • Li teaches that the calculated W_MF (v i , v j ) and W_CC (v i , v j ) denote the scores for the strengths of sharing molecular functions and cellular components of vi and vj, respectively (i.e. similarity criteria ) (pg. 63 col. 2 para. 3); wherein the growth process is repeated from all vertices to form non-redundant complex sets (pg. 66 col. 1 para. 1); wherein the algorithm identifies complexes according to the neighbors of all proteins in the network (pg. 66 col. 1 para. 2); wherein a new neighbor node is maintained if the weighed density of the candidate complex is more than a threshold and removed if less than a threshold (i.e. the scores will consequently change based on the determined protein sequences built based on assigned weights )(pg. 66 col. 1 para. 2). Claim 11-12 recite a computer-implemented method that performs the steps recited in claims 1-2, respectively . Li teaches claims 11-12 above as applied for claims 1-2, respectively . Claims 14, 17-20 are being interpreted as method claims (see 112b rejection above), reciting a computer-implemented method that performs the steps recited in claims 4 and 7-10, respectively . Li teaches claims 14, 17-20 above as applied for claims 4 and 7-10, respectively. Claim 21 recites a non-transitory computer readable storage medium related to the steps recited in claim 1 . Li teaches claim 21 as applied for claim 1 ; wherein data output is computationally stored in files (i.e. non-transitory computer readable storage medium ) (pg. 64 Fig. 2). Claim Rejections - 35 USC § 103 07-20-fti The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-fti The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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. A. Claims 3, 5, 13 and 15 are rejected under 35 U.S.C. 103(a) as being unpatentable over Li as applied to claims 1 and 11 in the 102 rejection above further in view of Mansheng ("The protein-protein interaction ontology: for better representing and capturing the biological context of protein interaction." BMC genomics 22(5):544 (2021)), as cited on the attached Form PTO-892. Claim 3 recites: wherein the one or more ontologies correspond to at least a protein ontology and a gene ontology • Li teaches constructing a multi-relationship protein interaction network by integrating PPI network topology with gene ontology annotation information (pg. 62 col. 2 para. 1). Li does not teach " a protein ontology ." However, Mansheng teaches a protein-protein interaction ontology describing PPIs (pg. 2 col. 1 para. 3) and the integration of appropriate terms from the corresponding vocabularies/ontologies, e.g., Gene Ontology, Protein Ontology (pg. 1 para. 2). Claim 5 recites: wherein the data that describes the primary target protein comprises at least sequence information, function classification information, metabolic pathway information, interaction profile, and Gene Ontology functional annotation of the primary target protein • Li teaches the prediction of protein complexes (i.e. comprising the primary target protein ) by using a gene ontology database (i.e. Gene Ontology functional annotation ) organized by MF (i.e. function classification information ), BP (i.e. metabolic pathway information ), and CC (pg. 63 col. 1 para. 2); wherein the multi-relationship network represents the interaction type (i.e. interaction profile ) for the set of proteins being investigated (pg. 62 col. 2 para. 3). Li does not teach "sequence information." However, Mansheng teaches a protein-protein interaction ontology describing PPIs (pg. 2 col. 1 para. 3); wherein sequence information is included in the protein ontology description (pg. 3 Table 1). Claims 13 and 15 are being interpreted as method claims (see 112b rejection above), reciting a computer-implemented method that performs the steps recited in claims 3 and 5, respectively . Li and Mansheng teach claims 13 and 15 above as applied for claims 3 and 5, respectively. Rationale for combining (MPEP §2142-2143) Regarding claims 3, 5, 13, and 15 , 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 combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Li in view of Mansheng because all references disclose methods for the investigation of the biological context of protein interaction. The motivation would have been to incorporate a PPI annotation, which involves temporal-spatial information of PPI at the cellular level (pg. 8 col. 2 para. 2 Mansheng ); Therefore it would have been obvious to one of ordinary skill in the art to substitute the allelic imbalance analysis method of Li to the methods by Mansheng because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of the biological context of protein interaction. B. Claims 6 and 16 are rejected under 35 U.S.C. 103(a) as being unpatentable over Li as applied to claims 1 and 11 in the 102 rejection above further in view of Ashtiani ("A systematic survey of centrality measures for protein-protein interaction networks." BMC systems biology 12(1):80 (2018)), as cited on the attached Form PTO-892. Claim 6 recites: wherein the protein-protein interaction is based on closeness centrality of the primary target protein with respect to the plurality of secondary target protein • Li does not teach the limitation above. However, Ashtiani teaches a systematic investigation of PPI network wherein closeness centrality measures demonstrated a high level contribution to characterize and assort influential nodes of the networks (pg. 1 para 2). Claim 16 is being interpreted as method claims (see 112b rejection above), reciting a computer-implemented method that performs the steps recited in claim 6 . Li and Ashtiani teach claim 16 above as applied for claim 6. Rationale for combining (MPEP §2142-2143) Regarding claims 6 and 16 , 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 combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Li in view of Ashtiani because all references disclose methods for the investigation of the biological context of protein interaction. The motivation would have been to incorporate a suitable set of centrality measures for inferring important functional properties of a PPI network (pg. 1 para. 3 Ashtiani ); Therefore it would have been obvious to one of ordinary skill in the art to substitute the allelic imbalance analysis method of Li to the methods by Ashtiani because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of the biological context of protein interaction. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET. 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, Olivia Wise can be reached at (571) 272-2249. 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. /F.F.L./Examiner, Art Unit 1685 /JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685 Application/Control Number: 17/978,305 Page 2 Art Unit: 1685 Application/Control Number: 17/978,305 Page 3 Art Unit: 1685 Application/Control Number: 17/978,305 Page 4 Art Unit: 1685 Application/Control Number: 17/978,305 Page 5 Art Unit: 1685 Application/Control Number: 17/978,305 Page 6 Art Unit: 1685 Application/Control Number: 17/978,305 Page 7 Art Unit: 1685 Application/Control Number: 17/978,305 Page 8 Art Unit: 1685 Application/Control Number: 17/978,305 Page 9 Art Unit: 1685 Application/Control Number: 17/978,305 Page 10 Art Unit: 1685 Application/Control Number: 17/978,305 Page 11 Art Unit: 1685 Application/Control Number: 17/978,305 Page 12 Art Unit: 1685 Application/Control Number: 17/978,305 Page 13 Art Unit: 1685 Application/Control Number: 17/978,305 Page 14 Art Unit: 1685 Application/Control Number: 17/978,305 Page 15 Art Unit: 1685 Application/Control Number: 17/978,305 Page 16 Art Unit: 1685 Application/Control Number: 17/978,305 Page 17 Art Unit: 1685 Application/Control Number: 17/978,305 Page 18 Art Unit: 1685 Application/Control Number: 17/978,305 Page 19 Art Unit: 1685 Application/Control Number: 17/978,305 Page 20 Art Unit: 1685 Application/Control Number: 17/978,305 Page 21 Art Unit: 1685 Application/Control Number: 17/978,305 Page 22 Art Unit: 1685 Application/Control Number: 17/978,305 Page 23 Art Unit: 1685 Application/Control Number: 17/978,305 Page 24 Art Unit: 1685 Application/Control Number: 17/978,305 Page 25 Art Unit: 1685 Application/Control Number: 17/978,305 Page 26 Art Unit: 1685