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 1-18, 37, and 39 are pending. Priority This application is a CON of application no. 1 6/875, 848, filed 05/15/2020, which is a DIV of application no. 14/498, 864, filed 09/26/2014, which claims benefit of application no. 61/883,838, filed 09/27/2013. The instant application has the effective filing date of 27 September 2013. Information Disclosure Statement The two information disclosure statements (IDS) submitted on 11/04/2022 are in compliance with the provisions of 37 CFR 1.97 , but appear to be duplicates. Accordingly, one information disclosure statement h as been considered by the examiner. Drawings The drawings, submitted on 11 /0 2 / 2 0 22 , are accepted by the examiner. Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Browser executable code is found in the specification on pages 15, 48, 61 and 66 . Claim Rejections - 35 USC § 112 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. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claim s 1-18 and 39 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention for the following reasons. Claim 1-18 and 39 recite identifying “ energetically favorable poses ,” wherein “ energetically favorable ” is relative term , that is not defined within the specification. The dependent claims are rejected on similar grounds, as they also fail to remedy the indefiniteness of the limitation. Claim s 11-12 recite “at least about,” without a limiting definition in the specification. Such terminology is relative and indefinite per MPEP 2173.05(b). To overcome th e rejection s above , please provide some objective standards for measuring the scope of the recited limitations. 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 1-18, 37, and 39 are rejected under U.S.C 101 because the claimed invention is directed to abstract ideas without significantly more, as detailed in the analysis below. Eligibility Step 1: Subject matter eligibility evaluation in accordance with MPEP § 2106: Claims 1-1 8 and 39 are directed to a statutory category ( method ). Claim 37 is directed to a statutory category ( system ). Therefore, in accordance with MPEP § 2106.03 all claims have patent eligible subject matter. [Eligibility Step 1: YES] Eligibility Step 2A : This step determines whether a claim is directed to a judicial exception in accordance with MPEP § 2106. Eligibility Step 2A -- Prong One: Limitations are analyzed to determine if the claims recite any concepts that could equate to a judicial exception (i.e. abstract idea, law of nature, or natural phenomenon). Recitations of Judicial Exceptions: Claims 1 , 37 , and 39 : s creening a plurality of different enzyme /protein variants for activity with a substrate /ligand ; (ii) identifies energetically favorable poses of the substrate in the active site; (b) for each energetically favorable pose, determining whether the pose is active, wherein an active pose meets one or more constraints for the substrate to undergo catalysis in the active site; and (c) selecting at least one of the enzyme variants determined to have one or more active poses. Claim 3: wherein the computational representation of the substrate represents a species along the reaction coordinate for the enzyme activity, the species being selected from the substrate, a reaction intermediate of the substrate, or a transition state of the substrate. Claim 6: wherein the plurality of variants comprise one or more enzymes that can catalyze a chemical reaction selected from oxidoreduction, transferation , hydrolysis, isomerization, ligation, and chemical bond breaking by a reaction other than hydrolysis, oxidation or reduction. Claim 7: wherein the enzyme is selected from oxidoreductase, transferase, hydrolase, isomerase, ligase, and lyase. Claim 8: wherein the plurality of variants comprise one or more enzymes that can catalyze a chemical reaction selected from ketone reduction , transamination, oxidation, nitrile, hydrolysis, imine reduction, enone reduction, acyl hydrolysis, and halohydrin dehalogenation. Claim 9: wherein the enzyme is selected from ketone reductase, transaminase, cytochrome P450 , Baeyer- Villiger , monooxygenase, monoamine oxidase, ni tri lase , imine reductase, enone reductase, acylase, and halohydrin dehalogenase Claim 16: wherein the method is applied to screen a plurality of substrates Claim 17: further comprising identifying the constraints for the substrate to undergo the catalyzed chemical transformation by identifying one or more poses of a native substrate, a reaction intermediate of the native substrate, or a transition state of the native substrate when the native substrate undergoes the catalyzed chemical transformation by a wild-type enzyme Claim 18: wherein the constraints comprise one or more of the following: position, distance, angle, and torsion constraints. Step 2A – Prong One Analysis: E lements that recite s creening , selecting, and identifying portions of data represent analysis techniques that m ake determinations of data requiring no more than the human mind and pen/paper. As such, limitations that recite these processes fall under the mental process groupings of abstract ideas. Limitations that merely provide additional information specifying the data of these limitations (claim s 16, 18) fall under the same grouping. Therefore, claims within the application are found to recite judicial exceptions. [Eligibility Step 2A – Prong One : YES ] Eligibility Step 2A – Prong Two: A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. If the claim contains no additional claim elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)). Additional Elements: Claims 1 , 37 , and 39 : f or each enzyme variant, docking, by the computer system, a computational representation of the substrate to a computational representation of an active site of the enzyme variant, wherein docking ( i ) generates a plurality of poses of the substrate in the active site, and (ii) identifies energetically favorable poses of the substrate in the active site; Claim 2: screening the at least one enzyme variant selected in (c) against the substrate by producing a chemical reaction Claim 4: wherein the plurality of enzyme variants comprise a panel of enzymes that can turn over multiple substrates and wherein the members of the panel possess at least one mutation relative to a reference sequence Claim 5: wherein the at least one mutation is a single-residue mutation in the active site of the enzyme Claim 10: wherein the plurality of variants comprises members of library produced by one or more rounds of directed evolution in vitro and/or in silico Claim 11: wherein the plurality of variants comprises at least about ten different variants Claim 12: wherein the plurality of variants comprises at least about a thousand different variants Claim 13: wherein the computational representations of active sites are provided from 3-D homology models for a plurality of variants. Claim 14: the method of claim 13, further comprising producing said 3-D homology models for the plurality of variant Claim 15: wherein the computational representation of the substrate is a 3-D model of the substrate Claims 1, 37, and 39: methods or systems implemented or comprising a computer that includes one or more processors and memory (computer components) Step 2A – Prong Two Analysis: Generating 3D representations of molecules for downstream analysis represent a data gathering activity necessary to carry out the processes of the claimed invention. The transformation does not qualify as a particular transformation per MPEP 2106.05(c). The generic computer components and implementations of a method onto a generic computing environment merely provide instructions to carry out the judicial exceptions per Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. When evaluated separately , and in the context of a whole claimed invention, the additional elements do not integrate the judicial exceptions into practical application. [Eligibility Step 2A – Prong Two: NO ] Eligibility Step 2B : Claim elements are probed for inventive concept equating to significantly more than the judicial exception (MPEP 2106.04(II)). Step 2B Analysis: Molecular docking of enzymes and proteins is found to be well-understood, routine, and conventional within the art per Sousa et al. (Proteins: Structure, Function, and Bioin .; 2006), which reviews the topic. Elements that represent generic computer components are considered well-understood, routine, and conventional per Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-9 3 for storing and retrieving information in memory. As such, the additional elements are further found to lack inventive concept. [Eligibility Step 2B : NO] Therefore claims 1-18, 37, and 39 are directed to judicial exceptions without significantly more and are rejected under 35 U.S.C 101. Claim Rejections - 35 USC § 102 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis ( 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim s 1-7 , 10, 15-18, 37, and 39 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Hermann et al. ( J. Am. Chem. Soc. Vol. 128; no. 49; 200 6 ) . Hermann et al. describes docking high-energy intermediates to enzyme structures. Claims 1 and 37 are directed to methods and systems that perform the following steps: generate multiple poses of a substrate in the active site of an enzyme variant; identif y energetically favorable poses of the substrate in the active site; determin e whether each energetically favorable pose is active if it meets one or more constraints for the substrate to undergo catalysis in the active site ; and select s at least one enzyme variants with one or more active poses . Hermann et al. teaches 21 docking predictions of enantioselectivity were made for the 24 possible mutant/substrate pairs (page 15890, column 1) , where substrates are docked into the monovalent enzyme active site s (page 15889, column 1). Hermann et al. further teaches t he best scoring pose was rigid-body minimized and scored for electrostatic and van der Waals interactions (page 15885, column 2). Hermann et al. further teaches set ting t he dielectric of a defined region in the active site potentially occupied by substrate atoms to 2 in order to account for the effect of substrate binding (page 15885, column 2); and filter ing a ll docked poses for consistency with our model of catalysis (page 15885, column 2). Hermann et al. further teaches indicating the absolute stereochemistry of the enantiomer preferred by the wild type and G60A mutant forms of phosphotriesterase (page 15890, table 2) of the 21 catalytically competent docking predictions (page 15890, column 1) . Claim 2 is directed to producing a chemical reaction to screen the enzyme variant against the substrat es. Hermann et al. teaches synthesizing (page 15889, column 2) , and hydrolyzing (15890, column 1) four compound s/ eight stereoisomers that were tested as substrates , to determine the stereoselectivity of the enzymes ( page 15889, column 2 ). Claim 3 is directed to the computational substrate representation being one of the following species reaction coordinates: substrate, a reaction intermediate of the substrate, or a transition state of the substrate . Hermann et al. teaches docking high-energy intermediate forms of the potential substrates (page 15882, abstract) . Claim 4 is directed to the enzyme variants being capable turning over substrates and hav ing at least one mutation relative to a reference sequence. Claim 5 is directed to the mutation being a single-residue mutation in the active site of the enzyme. Hermann et al . teaches reject ing molecules docked in catalytically nonproductive configuration s (page 15885, column 2) . Hermann et al. further teaches t he mutant enzymes differed from the wild type by only one to three active-site residues (page 15885, column 1 ). Claim 6 is directed to the variants being capable of catalyzing one of the following chemical reactions: oxidoreduction, transferation , hydrolysis, isomerization, ligation , or chemical bond breaking by a reaction other than hydrolysis, oxidation or reduction. Hermann et al. teaches predicting the enantioselectivities of the amidohydrolase phosphotriesterase and five of its mutant enzymes ( page 15883, column 2 ) , where a lmost all of the structurally characterized enzymes in this superfamily catalyze hydrolytic reactions ( page 15884, column 1 ) , except uronate isomerase, which catalyzes an aldose/ketose isomerization ( page 15884, column 1 ) . Claim 7 is directed to the enzyme being classified as one of the following : oxidoreductase, transferase, hydrolase, isomerase, ligase, or lyase . Hermann et al. teaches limit ing the study to amidohydrolases (page 15883, column 1). Claim 10 is directed to the variants including members of library, produced by one or more rounds of directed evolution in vitro and/or in silico . Hermann et al. teaches that since a crystal structure of a related phosphotriesterase mutant differs from the wild-type protein by only 0.47 Å RMSD in the α-carbons and had no major backbone movements, the mutant enzymes were modeled by simple modifications of the side chains of the wild-type structure (15885, column 1) . Therefore , Hermann et al. teaches producing enzyme variant s via artificially mutating one or more biomolecule sequences, in accordance with the specification. Claim 15 is directed to the computational representation of a substrate being a 3D model. Hermann et al. teaches a ll structures were converted from isomeric SMILES to 3D structures (page 15884, column 2). Claim 16 is directed to using the method of claim one for screening two or more substrates. Hermann et al. teaches b y only modeling metabolites and related molecules, the possible number of substrates was reduced from the googol levels quoted for chemical space to about 4000 (15890, column 2). Claim 17 is directed to identifying one of more poses of native substrate, reaction intermediate of the native substrate, or transition state of the native substrate when the substrate undergoes a catalyzed chemical transformation via a wild type enzyme; and using the process to identify the constraint for the substrate to undergo the catalyzed chemical transformation. Hermann et al. teaches docking high-energy intermediate forms of the potential substrates (page 15882, column 1); and filtering a ll docked poses for consistency with our model of catalysis … by insisting that reactive substructures be within 3.5 Å of the catalytic nucleophile (page 15885, column 2) . Claim 18 is directed to the constraints including one or more of the following: position, distance, angle, or torsion. Hermann et al. teaches the distance tolerance for matching a receptor and a ligand sphere was set to 1.5 Å. (page 15885, column 2). Claim 39 is directed to docking ligand s into the active sit e of protein variants , using an otherwise identical method of claim one . Hermann et al. teaches penaliz ing c onfigurations for desolvation using the precalculated AMSOL ligand desolvation energies, weighted for the degree of burial of each substrate atom by the protein (page 15885, column 2). Therefore Hermann et al. teaches the enzyme variant -substrate docking method described , as a species of protein variant -ligand docking . Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis ( i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim s 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Hermann et al. ( J. Am. Chem. Soc. Vol. 128; no. 49; 2006 ) as applied to claims 1-7 , 10, 15-18, 37, and 39 above , in view of Liaw et al . (Journal of Biological Chemistry; Vol. 278 (7); 2003) . Hermann et al. teaches a method of screening wild type and mutant amidohydrolase enzymes via molecular docking , as described above . Hermann et al. further teaches the a pplication of this structure-based approach for substrate prediction to enzymes of unknown function merits further study (page 15891, column 2). Hermann et al. does not teach screening enzyme variants capable of catalyzing one of: ketone reduction, transamination, oxidation, nitrile hydrolysis, imine reduction, enone reduction, acyl hydrolysis, or halohydrin dehalogenation ( claim 8 ); nor to the enzymes being classified as one of the following : ketone reductase, transaminase, cytochrome P450 , Baeyer- Villiger , monooxygenase, monoamine oxidase, nitrilase , imine reductase, enone reductase, acylase , or halohydrin dehalogenase ( claim 9 ). Liaw et al. describes the structure and mechanisms of D- aminoacylase . Liaw et al. teaches D- aminoacylase is an attractive candidate for commercial production of D-amino acids through its catalysis in the hydrolysis of N -acyl-d-amino acids (page 4957, column 1). Liaw et al. further teaches the enzyme structure shares significant similarity to the α/β-barrel amidohydrolase superfamily (page 4957, column 1 ) . Therefore Hermann et al. teaches performing a method of screening mutant amidohydrolases enzymes and provides sufficient motivation for one of ordinary skill in the art to apply the method on alternative enzymes. Liaw et al. teaches an acylase, D- aminoacylase , catalyzes an acyl hydrolysis reaction and is closely related to enzymes with in the amidohydrolase family. Therefore, it would be obvious for one of ordinary skill in the art to apply the enzyme screening method of Hermann et al. to D- aminoacylase variants with a reasonable expectation of success . Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hermann et al. ( J. Am. Chem. Soc. Vol. 128; no. 49; 2006 ) , as applied to claim s 1-7 , 10, 15-18, 37, and 39 previously, in view of Reetz ( J. Org Chem; Vol. 74; 2009 ) . Hermann et al. teaches a method of scree n ing five different mutant enzymes for enantioselectivity via molecular docking, as described previously . Hermann et al. does not teach screening at least 10 ( claim 11 ) or at least 1000 ( claim 12 ) different variants. Reetz describes the directed evolution of enantioselective enzymes. Reetz teaches a method that includes screening libraries of mutant enzymes, that can range from a few hundred to millions, for a given protein property, and subject ing the gene of the best mutant (hit) to further mutagenesis/screening (page 5768, column 1) . Reetz further teaches one of the main challenge s of this scheme is developing high-throughput screening systems for the rapid evaluation of the enantiomeric purity of thousands of samples (page 5768, column 2) . Reetz further teaches analyzing the results of docking the substrate into the WT and mutant enzymes (page 5775, fig. 11), not only illuminates the source of enhanced enantioselectivity on a molecular level but also deepens our understanding of the details of how the enzyme functions (page 5775, column 2) . Therefore Hermann et al. teaches a method of screening five different mutants via molecular docking for enantiosel ecti vi ty . Reetz teaches a method of screening a large library of mutants which utilizes molecular docking technique as a key component. Therefore, it would be obvious for one of ordinary skill in the art would to combine the docking technique, as taught by Hermann et al., within the directed evolution-based screening technique of Reetz , with a reasonable expectation of success. Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hermann et al. ( J. Am. Chem. Soc. Vol. 128; no. 49; 2006 ) , as applied to claims 1-7 , 10, 15-18, 37, and 39 previously, in view of Cavasotto et al. ( Drug Discovery Today; Vol. 14 ; no. 13/14; 2009) . Hermann et al. teaches a method of screening wild type and mutant enzymes via molecular docking, as described previously. Hermann et al. further teaches convert ing a ll structures from isomeric SMILES to 3D structures using CORINA (page 15884, column 2); and that the structures of many proteins are available through comparative modeling of close homologues (page 15882, column 1). Hermann et al. does not explicitly teach obtaining computational active site representations via 3D homology models ( claim 13 ), nor producing 3D homology models ( claim 14 ). Cavasotto et al. revie w s trends and applications of homology modeling in drug discovery. Cavasotto et al. teaches the process of homology and comparative modeling of proteins consists of: (1) identification of known 3D structure(s) of a related protein that can serve as template , (2) sequence alignment of target and template proteins , and (3) model building for the target based on the 3D structure of the template and the alignmen t (page 677, column 1). Cavasotto et al. further teaches use s of homology m odels include generating d ocking and scoring protocol s for the enolase family to rank the known substrates of enolase family members ( page 678, column 2 ) and conduct ing mutagenesis experiments on the active site residues (page 680, column 1). Therefore, Hermann et al. obtains 3D representations of enzyme structures and provides sufficient motivation for one of ordinary skill in the art to utilize homology modelling in order to gain additional information on the enzyme structures . Cavasotto et al. teaches a method of producing homology models to complete the same function within molecular docking experiment s . Therefore, it would be obvious to one of ordinary skill in the art to apply the method of Cavasotto et al. to produce active site homology models , based on the teachings of Hermann et al. Conclusion No claims are currently allowed. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to Milana Thompson whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8740 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday, 9:00-6:00 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. / M.K.T ./ Examiner, Art Unit 1687 /Karlheinz R. Skowronek/ Supervisory Patent Examiner, Art Unit 1687