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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 1-14 are currently pending. Claims 1, 2, 6-11, 13 and 14 have been amended by Applicants’ amendment filed 07-21-2026. No claims have been added or canceled by Applicants’ amendment filed 07-21-2026.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 1-14 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed September 11, 2023, is a DIV of US Patent Application 17722081 (now US Patent 11752195), filed April 15, 2022, which claims the benefit of US Provisional Patent Application 63175263, filed April 15, 2021.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application 63/175263, filed April 15, 2021, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for; “a library of peptides having 15-18 amino acid residues in length” in line 2; and “selected from the group consisting of: L-alanine, D-alanine, D-aspartic acid…and D-tyrosine” in lines 3-8; and “a relative fluorescence unit that is at least 10 times the median signal of the fluorescence signal of the peptide microarray” in lines 16-17. Therefore, the priority date for the presently claimed invention is April 15, 2022, the filing date of US Patent Application 17/722,081.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claims 1-14 of the instant application.
Information Disclosure Statement
No information disclosure statement has been filed in the instant application. Applicants are reminded of their duty to disclose all information known to them to be material to the patentability as defined in 37 C.F.R. 1.56.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed July 21, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
Maintained Objections/Rejections
Claim Interpretation
The term “administering a candidate peptide selected from the peptides bound to the fluorescently labeled bacterial cells to a culture of bacterial cells” as recited in claim 1 to mean that the selected peptide can be administered to a culture of a bacterial cells in any form, such as administering a bound peptide directly from the array, administering a purified peptide, administering a synthesized or re-synthesized peptide, etc.
Claim Objections
The objection to claims 8 and 9 is maintained because of the following informalities: Claims 8 and 9 recite abbreviated terms including: “mm” where an abbreviation should be spelled out in the first encounter of the claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1-14 is maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the terms “measuring fluorescence emitted” and “fluorescence signal of the peptide microarray” such as recited in claim 1, lines 16 and 17 because claim 1 does not recite the emission of a fluorescence signal and/or when fluorescence is emitted (e.g., such as when bacterial cells bind a peptide on the microarray), such that it is unclear when fluorescence occurs, why fluorescence is emitted, and/or why a signal is generated and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “the peptide array” such as recited in claim 1, line 16. There is insufficient antecedent basis for the term “the peptide array” in the claim because claim 1, lines 14-15 recite the term “the peptide microarray”. The Examiner suggests that Applicant amend the claim to recite, for example, “emitted from the peptide microarray”.
Claim 1 is indefinite for the recitation of the term “calculate a median signal” such as recited in claim 1, line 16 because it is unclear whether a median signal is calculated given that a step of “calculating a median signal” is not positively recited in claim 1. Moreover, it is unclear what “median signal” is being calculated. It is unclear whether all fluorescently labeled bacterial cells spontaneously emit a fluorescent signal, such that a median of all the combined signals is calculated, whether only a portion of the fluorescently labeled bacterial cells spontaneously emit a fluorescent signal, such that the median signal is a median of some group, whether this median signal is compared to some reference signal, and/or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “identifying peptides that have a relative fluorescence unit that is at least 10 times the median signal” such as recited in claim 1, lines 18-20 because the peptides are not fluorescently labeled, such that the peptides of the microarray cannot have a relative fluorescence unit. Moreover, claim 1 does not recite that the peptides emit a fluorescence signal. Additionally, it is unclear as to the identity of a ‘relative fluorescence unit’, how a ‘relative fluorescence unit’ is calculated and/or how it is related to the median signal. Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993) and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the terms “thereby identifying peptides that bound to fluorescently labeled bacterial cells” and “the peptides bound to the fluorescently labeled bacterial cells” such as recited in claim 1, lines 21-23 because claim 1 does not positively recite a step wherein the peptides of the microarray bind to the fluorescently labeled bacterial cells; and/or the binding of peptides to fluorescently labeled bacterial cells and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “a candidate peptide selected from the peptides bound to the fluorescently labeled bacterial cells” such as recited in claim 1, lines 22-23 because claim 1 does not recite a step of “selecting a peptide”, and/or identifying a selected peptide as a “candidate peptide” and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “synthetic antimicrobial peptides” such as recited in claim 1, line 26 because it is unclear how any identified candidate peptide is considered a “synthetic antimicrobial peptide”. Amended claim 1 does not recite that the synthesis of any peptide, and it is unclear whether peptides comprising same structure that are not “synthesized”, would show the same activity in a cellular growth assay and, thus, the metes and bounds of the claim cannot be determined.
The rejection of claim 3 is maintained as being indefinite for the recitation of the term “wherein the method identifies synthetic antimicrobial peptides against a target bacterial species, the suspension of bacterial cells…the target bacterial species” such as recited in claim 3, lines 1-3 because claim 3 depends from instant claim 1, wherein claim 1 does not recite the presence of a “target bacterial species” (claim 1 recites “bacterial cells”). Moreover, claim 1 recites that the method comprises generating, attaching, providing, incubating, measuring, identifying, administering, measuring and identifying a candidate peptide, such that claim 3 cannot recite that the method, instead, comprises identifying synthetic antimicrobial peptides against a target bacterial species and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “sequesters metal ions” such as recited in claim 6, line 4 because amended claim 6 depends from amended claim 1, wherein instant claim 1 does not recite the presence of metal ions, such that it is unclear why a candidate peptide is administered with a chelator and, thus, the metes and bounds of the claim cannot be determined.
The rejection of claim 10 is maintained as being indefinite for the recitation of the term “target bacterial species” such as recited in claim 10, lines 1-2 because claim 10 depends from instant claim 1, wherein claim 1 does not recite the presence of target bacterial cells and/or target bacterial species and/or and, thus, the metes and bounds of the claim cannot be determined.
Claims 2, 4, 5, 7-9 and 11-14 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The rejection of claims 3, 6 and 10 is maintained under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 3 and 10 recite (in part): “target bacterial species” in claim 3, line 2 because claims 3 and 10 depend from instant claim 1, wherein claim 1 does not recite the presence of a target bacterial species. Moreover, claim 3 recites that the method comprises a different step than what is recited in instant claim 1. Thus, claims 3 and 10 are improper dependent claims for failing to further limit the subject matter of the claim upon which they depend, or for failing to include all the limitations of the claim upon which they depends.
Claim 6 recites (in part): “administering the candidate peptide together with a chelator that sequesters metal ions” in claim 6, lines 2-3 because claim 6 depends from instant claim 1, wherein claim 1 does not recite the presence of metal ions. Thus, claim 6 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Response to Arguments
Applicants’ arguments filed July 21, 2026 have been fully considered but they are not persuasive. Applicants essentially asserts: (a) regarding claim 3, it is noted that claim 3 introduces a conditional further limitation that restricts the scope of claim 1 (Applicant Remarks, pg. 7, paragraph B).
Regarding (a), regarding claim 3, the term “target bacterial species” has no basis in the claim from which it depends. Moreover, claim 3 recites:
“the method of claim 1, wherein the method identifies synthetic antimicrobial peptides against a target bacterial species”
wherein claim 3 recites that the method comprises something different than what it is recited to comprise in independent claim 1. Additionally, claim 3 depends from claim 1, wherein claim 1 does not recite the presence of a target bacterial species, such that claim 3 recites limitations that have no basis in the claim from which they depend. The Examiner suggests that Applicant amend claim 3 to recite, for example, “the method of claim 1, further comprising identifying a target bacterial species” or perhaps, “wherein the culture of bacterial cells is a mixture of target bacterial species”. The claims remain rejected.
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.
The rejection of claims 1-14 is maintained under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. An analysis with respect to the claims as a whole reveals that they do not include additional elements that are sufficient to amount to significantly more than the judicial exception. See Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 110 U.S.P.Q.2d 1976 (2014); Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116, 106 U.S.P.Q.2d 1972 (2013); Mayo Collaborative Svcs. v. Prometheus Laboratories, Inc., 132 S. Ct. 1289, 101 U.S.P.Q.2d 1961 (2012). See also 2014 Interim Guidance on Patent Subject Matter Eligibility, available at http://www.gpo.gov/ fdsys/pkg/FR-2014-12-16/pdf/2014-29414.pdf (“2014 Interim Guidance”), and the Office’s examples to be considered in conjunction with the 2014 Interim Guidance in examination of nature-based products, available online at http://www.uspto.gov/patents/law/exam/mdc_examples_nature-based_products.pdf (“Nature-Based Products Examples”). This rejection is proper.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of three issues: (1) whether the claim is directed to one of the four categories recited in §101; (2) whether the claim recites or involves a judicial exception (i.e., abstract idea, a law of nature, natural phenomenon, or natural product); and (3) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. In this case, the claims as a whole are directed to an abstract idea. Therefore, they must each be considered to determine whether, given their broadest reasonable interpretation, they amount to significantly more than the judicial exception.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 1-14 do not recite something significantly different than the judicial exception. The rationale for this determination is explained below:
In the instant case, the claims broadly directed to a method of identifying synthetic antimicrobial peptides, the method comprising: (a) generating a library of peptides having 15-18 amino acid residues in length using amino acids selected from the group consisting of: L-alanine, D-alanine, L-aspartic acid, D-aspartic acid, L-glutamic acid, D glutamic acid, L-phenylalanine, D-phenylalanine, L-glycine, L-histidine, D-histidine, L-isoleucine, D isoleucine, L-lysine, D-lysine, L-leucine, D-leucine, L-methionine, D-methionine, L-asparagine, D asparagine, L-proline, D-proline, L-glutamine, D-glutamine, L-arginine, D-arginine, L-serine, D-serine, L-threonine, D-threonine, L-valine, D-valine, L-tryptophan, D-tryptophan, L-tyrosine, and D-tyrosine; (b) attaching the library of peptides on a silicon wafer, wherein the silicon wafer is coated with a photoresist and a photoacid generator to produce a peptide microarray; (c) providing a suspension of bacterial cells, wherein the bacterial cells are fluorescently labeled; (d) incubating the suspension of fluorescently labeled bacterial cells with the peptide microarray; (e) incubating the suspension of bacterial cells with the peptide microarray; (f) measuring fluorescence emitted from the peptide array to calculate a median signal from fluorescence signal of the peptide microarray; (g) identifying peptides that have a relative fluorescence unit that is at least 10 times the median signal of the fluorescence signal of the peptide microarray, thereby identifying peptides bound to fluorescently labeled bacterial cells; (h) administering a candidate peptide selected from the peptides bound to fluorescently labeled bacterial cells to a culture of bacterial cells; (i) measuring growth of the culture of bacterial cells; and (j) identifying the candidate peptide that inhibit the growth of the culture of bacterial cells as synthetic antimicrobial peptides
Beginning with Step I of the analysis, which asks whether the claimed invention falls within a statutory category, such that the instant claims are directed to a process, thus, the instant claims are directed to a statutory category. Step I: [YES].
Proceeding to revised Step IIA – Prong One of the analysis, which asks if the claimed invention is directed to a judicial exception, such that claims 1-14 are directed to a natural phenomenon in the form of a natural correlation between naturally occurring peptides, and the ability of peptides to inhibit the growth of bacterial cells; and to an abstract idea including: (a) mathematical concepts such as mathematical relationships, formulas or equations, and/or calculations in the form of measuring fluorescence; calculating median signal from the fluorescence signal of the peptide microarray, identifying peptides having a relative fluorescence unit at least 10x the median signal, measuring growth of the bacterial cell culture, etc.; as well as, (b) mental processes such as concepts performed in the human mind, such as observation, evaluation, judgement and opinion in the form of identifying peptides that have an RFU, identifying a candidate peptide bound to fluorescently labeled bacterial cells; identifying peptides that inhibit growth of a culture of bacterial cells, etc. The claims recite the judicial exception of a natural phenomenon, and an abstract idea that fall within the groupings of abstract ideas enumerated in the 2019 PEG including encompassing mathematical concepts, mental processes that can be carried out in the human mind, and/or by using a generic computer that performs routine and conventional functions including concepts including executing mathematical concepts, such as mathematical relationships, formula, equations, calculations. Thus, under the revised Step IIA analysis, the claims are directed to an abstract idea. Step IIA – Prong One [YES].
Step IIA - Prong Two asks whether the claim recites additional elements that integrate the exception into a practical application of the exception. In the instant case, the claims are directed to a judicial exception in the form of a natural phenomenon and an abstract idea. Claim 1 recites: “identifying synthetic antimicrobial peptides” in line 1; “incubating the suspension of fluorescently labeled bacterial cells with the peptide microarray” in lines 14-15; “measuring fluorescence emitted from the peptide array to calculate a median signal from fluorescence signal of the peptide microarray;” in line 16-17; “identifying peptides that have a relative fluorescence unit that is at least 10 times the median signal of the fluorescence signal of the peptide microarray, thereby identifying peptides bound to fluorescently labeled bacterial cells;” in lines 18-21; “administering a candidate peptide selected from the peptides bound to fluorescently labeled bacterial cells to a culture of bacterial cells; measuring growth of the culture of bacterial cells;” in lines 22-23; and “identifying the candidate peptide that inhibit the growth of the culture of bacterial cells as synthetic antimicrobial peptides;” in lines 25-26. These limitations simply describe a process of collecting and analyzing information, which is analogous to “obtaining and comparing intangible data” (i.e. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 99 U.S.P.Q.2d 1690 (Fed. Cir. 2011)); as well as, “collecting information, analyzing it, and displaying certain results of the collection analysis” (i.e. Electric Power Group, LLC, v. Alstom, 830 F.3d 1350, 119 U.S.P.Q.2d 1739 (Fed. Cir. 2016)). Moreover, many of Applicant’s process steps can be practiced as a mental process performed in the human mind, by pen and paper, or through the use of a generic computer, for example, “comparing information regarding a sample or test subject to a control or target data” (i.e. Univ. of Utah Research Found. v. Ambry Genetics Corp. (Also known as In re BRCA1– and BRCA2–Based Hereditary Cancer Test Patent Litigation), 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) or Association for Molecular Pathology v. USPTO (Also known as Myriad CAFC), 689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)). Additionally, the dependent limitations of claims 2-14 also suffer from the same issue. In other words, the dependent limitations do not rectify the rejection of the independent claim. By way of example, the limitations of claim 2 provides, “further comprising screening the candidate peptide for antimicrobial properties against other bacterial species, wherein the other bacterial species is different than the target bacterial species;” which clearly resembles “organizing information through mathematical correlations” (i.e. Digitech Image Techs., LLC v Electronics for Imaging, Inc., 758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)); and is analogous to “obtaining and comparing intangible data” (i.e. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 99 U.S.P.Q.2d 1690 (Fed. Cir. 2011)); “collecting information, analyzing it, and displaying certain results of the collection analysis” (i.e. Electric Power Group, LLC, v. Alstom, 830 F.3d 1350, 119 U.S.P.Q.2d 1739 (Fed. Cir. 2016)); and “comparing information regarding a sample or test subject to a control or target data” (i.e. Univ. of Utah Research Found. v. Ambry Genetics Corp. (Also known as In re BRCA1– and BRCA2–Based Hereditary Cancer Test Patent Litigation), 774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) or Association for Molecular Pathology v. USPTO (Also known as Myriad CAFC), 689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)). The claims do not provide other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment, e.g., an immunization step that integrates an abstract idea of data comparison into a specific process of immunizing that lowers the risk that immunized patients will later develop chronic immune-mediated diseases, as discussed in Classen Immunotherapies Inc. v. Biogen IDEC, 659 F.3d 1057, 1066-68, 100 USPQ2d 1492, 1499-1502 (Fed. Cir. 2011) (see MPEP § 2106.05(e)). Thus, the claims do not integrate the judicial exceptions into a practical application of the exceptions. Step IIA – Prong Two [NO].
Proceeding to Step IIB of the analysis: the question then becomes what element or what combination of elements is sufficient to amount to significantly more than the abstract idea?
The instant independent claim is recited at a high level of generality, such that substantially all practical applications of the judicial exception are covered. For instance, claim 1 is recited without any specificity as to the method of generating a library of peptides; the library of peptides generated; the specific number of amino acid residues; the number of peptides generated; the specific peptide structures; the method of attaching the peptides; the size of the silicon wafer; the coating; the photoacid generator, linkers, anchor groups, etc. attached to the wafer; the method of providing a suspension; the identity of the bacterial cells; the fluorescent label; the method of incubating; the specific cells; what the cells are suspended in; the method of identifying peptides bound to the fluorescently labeled bacterial cells; the fluorescently labeled bacterial cells; the relative fluorescence unit; the median signal of the peptide microarray; the method of administering peptides bound to the fluorescently labeled bacterial cells; the identity of the peptide and/or bacterial cells administered; the method of identifying peptides that inhibit growth of a culture of bacterial cells; the specific bacterial cells; the amount of inhibition in growth; the specific antimicrobial peptides, etc., wherein the steps of the method are well-known, purely conventional or routine in the art.
For example, peptide arrays that bind cells including bacterial cells, where specific binding can be defined as a binding strength (e.g., fluorescence intensity) more than three standard deviations greater than background represented by the mean binding strength of empty control areas in an array; and signals on the array varied over 3 logs of fluorescence intensity; and comparison of the relative fluorescence intensities of recognized peptides to the profile identified peptides whose intensities over time matched the defined profile with a Pearson correlation of greater than 0.9. Profile analysis was similarly used to identify sets of peptides whose recognition was increased after immunization but diminished after challenge and those that were initially recognized at day 0 but were no longer recognized following immunization were known in the art as evidenced by Johnston (US20120190574; Abstract, paragraphs [0007]; [0033]; [0073]; [0075]; [0096]; and [0107]); the production of peptide arrays comprising about 5 to 20 amino acids was known in the art including synthesizing peptide arrays on a silicon wafer using photoacid or photobase generators, wherein the pattern of the array is defined using a photomask as evidenced by Rajasekaran (WO2014078606; paragraph [0006]; [0055]; [0059]; and [00167]). Additionally, natural peptide antibiotics having amino acid lengths of 15-18 residues are known in the art including temporins, which are peptides found in amphibian skin (first isolated from the skin secretions of specimens of the European red frog Rana temporaria), which constitute the largest family of AMPs, with more than 100 isoform, wherein temporins are among the smallest AMPs (10-14 residues long) as evidenced by Mangoni (Journal of Medicinal Chemistry; pg. 1298, col 2, last partial paragraph; and pg. 1299; Table 1); as well as, protegrins (PG) are cathelicidins from porcine white blood cells (WBCs) that are arginine and cysteine-rich cationic AMPs of 16–18 amino acids with a b-hairpin structure containing two disulfide bonds, wherein the protegrin family consists of five members (PG1–5), such that PG1, the most thoroughly investigated protegrin, is active against E. coli, P. aeruginosa, E. faecalis, and S. aureus (MRSA), while PG4 is active against B. subtilis; and bactenecins are AMPs rich in arginine that have been isolated from bovine, ovine, and caprine neutrophilic granules, wherein their activity is primarily directed against Gram negative bacteria and they are cytotoxic for rat embryonic neurons, fetal rat astrocytes, and human glioblastoma cells; such that bacterial killing results from membrane permeabilization and blockage of RNA synthesis as evidenced by Hafeez (International Journal of molecular Science; pg. 11, last partial paragraph). Moreover, the methods of identifying peptides are known in the art including wherein (1) whole bacteria are screened against the 10,000 random-sequence peptides microarray; (2) pathogen specific peptides with binding or lytic action are identified from a microarray functional screening assay and (3) combining binding and lytic peptides produces synbodies with activity against a particular pathogen (Figure 1A), such that by screening whole bacteria, we have the ability to profile any possible pathogen without selecting specific surface components, such as lipoteichoic acids, proteins and peptidoglycans for Gram-positive bacteria or lipopolysaccharides (LPS) for Gram-negative bacteria, wherein the microarray based functional assay distinguishes between peptides with antimicrobial activity and those that bind without affecting growth providing a large source of pathogen specific peptides that can be identified in a rapid manner including using a diverse set of bacteria to test the general applicability of this approach and screened Gram-negative bacteria, Escherichia coli O111:B4 (EC) and Pseudomonas aeruginosa (PA); and Gram-positive bacteria Streptococcus mutans (SM), Staphylococcus aureus (SA) and Bacillus subtilis (BS) against the 10,000 peptide library as evidenced by Domenyuk (PLoS One; pg. 1, col 2, last partial paragraph; pg. 2, col 1; and pg. 2, col 2); and where it is known that a range of pathogens (10 viruses and 11 bacteria) can be screened against a library of 10,000 peptides to identify shared and specific pathogen binding peptides, wherein a total of 275 peptides were selected for secondary binding screening and down-selected for cellular toxicity, such that peptides with confirmed binding and minimal toxicity were selected for inclusion into the pathogen binding peptide microarray; and (B) workflow for discovery of antimicrobial synbodies, wherein new or unknown pathogen is fluorescently labeled and screened against the pathogen binding 100-peptide microarray, such that peptides that bind the pathogen are selected and conjugated to a synbody scaffold to produce a synbody library for activity and toxicity testing in a series of in vitro functional assays to select antimicrobial synbodies for additional development; as well as, determining bacterial growth inhibition using an adapted version of the broth microdilution method in which peptides or synbodies to bacterial suspensions of ~106 CFU/mL in Mueller-Hinton Broth (MHB) in 96-well polypropylene plate as evidenced by Johnston (Scientific Reports; pg. 2, Figure 1; and pg. 10, MIC Assay). Furthermore, it was known that an array of random peptide ligands including on a silicon wafer can be treated with bacterial cells and fluorescent signals measured as evidenced by Kodadek (paragraphs [0011]; [0012]; [0020]; [0054]; [0090]; [0096]; and [0100]); and it was known that antimicrobial peptides with activity against S. aureus were tested against a bacterial suspension, wherein the AMP prevented visible growth, and minimal inhibitory concentrations were measured as evidenced by Dangel (Abstract, and pg. 4477, col 2, Microorganisms & Antimicrobial Assay). Thus, the claims as a whole simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality to the judicial exception, wherein the steps are well-understood, routine and conventional activities previously known to the industry, as discussed in Alice Corp., 134 S. Ct. at 2359-60, 110 USPQ2d at 1984 (see MPEP § 2106.05(d)). Step IIA [YES].
In sum, when the relevant factors are analyzed, the claims as a whole do NOT recite additional elements that amount to significantly more than the judicial exception itself. Accordingly, claim 1 DOES NOT qualify as eligible subject matter.
Dependent claims 2-14 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 101 because they do not add anything that makes the natural phenomenon in claim 1, significantly different. For example, claim 13 encompasses the method of claim 1, wherein screening the peptides bound to the fluorescently labeled bacterial cells for antimicrobial properties against other bacterial species comprises administering the peptides bound to the fluorescently labeled bacterial cells to a second culture of bacterial cells, but it does not add anything that makes the natural phenomenon and abstract idea in claim 1 significantly different. In light of the above consideration and the new guidance, claims 1-14 are non-statutory. This rejection is newly recited as necessitated by the new Guidance set forth in the Memorandum of July 30, 2015 updating the June 25, 2014 guidance (see June 25, 2014 memorandum from Deputy Commissioner for Patent Examination Policy Andrew Hirshfeld titled Preliminary Examination Instructions in view of the Supreme Court Decision in Alice Corporation Pty. Ltd. v. CLS Bank International, et al. (Alice Corp. Preliminary Examination Instructions) and the Revised Patent Subject Matter Eligibility Guidance (See, Federal Register, vol. 84, No. 4, January 7, 2019).
Response to Arguments
Applicants’ arguments filed July 21, 2026 have been fully considered but they are not persuasive. Applicants essentially asserts: (a) claim 1 does not merely collect information or state a natural correlation, claim 1 requires the steps of generating a library of peptides using amino acids, attaching peptides to a wafer, providing a suspension of bacterial cells, incubating the microarray with fluorescently labeled bacterial cells; applying the recited RFU threshold to select a candidate peptide; administering that physical candidate peptide to a bacterial culture; measuring culture growth; and identifying the candidate as antimicrobial based on the measured inhibition, wherein these laboratory operations cannot, as a practical matter, be performed in the human mind (Applicant Remarks, pg. 8, first full paragraph); (b) claim 1 integrates that concept into a practical application under Step 2A, Prong Two, the selected candidate peptide is then administered to a bacterial culture, culture growth is measured, and antimicrobial activity is determined (Applicant Remarks, pg. 8, second full paragraph); and (c) the ordered combination of steps recites significantly more than the judicial exception; none of the cited references shows routine use of the claimed threshold to select a physical candidate peptide from a synthetic peptide library lacking a known positive binder and then validate antimicrobial function in a growth assay, such that the claims recite significantly more than the judicial exception (Applicant Remarks, pg. 8, last partial paragraph through pg. 9, first partial paragraph).
Regarding (a), the Examiner notes that the steps recited in instant claim 1 are well known, purely conventional or routine in the art. For example, the cited references teach:
Producing peptide arrays that bind cells including bacterial cells; and identifying sets of peptides whose recognition was increased after immunization but diminished after challenge and those that were initially recognized at day 0 but were no longer recognized following immunization were known in the art as evidenced by Johnston.
Synthesizing peptide arrays on a silicon wafer using photoacid or photobase generators, wherein the pattern of the array is defined using a photomask as evidenced by Rajasekaran.
Identifying bactenecins, which are AMPs rich in arginine that have been isolated from bovine, ovine, and caprine neutrophilic granules, wherein their activity is primarily directed against Gram negative bacteria and they are cytotoxic for rat embryonic neurons, fetal rat astrocytes, and human glioblastoma cells; such that bacterial killing results from membrane permeabilization and blockage of RNA synthesis as evidenced by Hafeez.
The use of microarray based functional assay distinguishes between peptides with antimicrobial activity and those that bind without affecting growth providing a large source of pathogen specific peptides that can be identified in a rapid manner including using a diverse set of bacteria to test the general applicability of this approach and screened Gram-negative bacteria, Escherichia coli O111:B4 (EC) and Pseudomonas aeruginosa (PA); and Gram-positive bacteria Streptococcus mutans (SM), Staphylococcus aureus (SA) and Bacillus subtilis (BS) against the 10,000 peptide library as evidenced by Domenyuk.
Determining the relative fluorescence units (RFU) for each peptide from binding of pdm09 H1N1 peptides; and carrying out bacterial and viral screening against 10,000 peptide microarrays identifies common and specific pathogen binding peptides, creating a heat map of peptides (x-axis) that bound pathogens (y-axis), wherein positive peptides were defined as those with median normalized signal >2x background or >1.5x higher than the detection antibody control, such that for bacteria screened with the IC and CW labeling assay, wherein peptides that bind the pathogen are selected and conjugated to a synbody scaffold to produce a synbody library for activity and toxicity testing in a series of in vitro functional assays to select antimicrobial synbodies for additional development; as well as, determining bacterial growth inhibition using an adapted version of the broth microdilution method in which peptides or synbodies to bacterial suspensions of ~106 CFU/mL in Mueller-Hinton Broth (MHB) in 96-well polypropylene plate as evidenced by Johnston.
An array of random peptide ligands including on a silicon wafer can be treated with bacterial cells and fluorescent signals measured as evidenced by Kodadek.
Antimicrobial peptides with activity against S. aureus were tested against a bacterial suspension, wherein the AMP prevented visible growth, and minimal inhibitory concentrations were measured as evidenced by Dangel.
The claims as a whole recite judicial exceptions and steps that are well known, purely conventional or routine in the art. Thus, the claims remain rejected.
Regarding (b), Applicant’s assertion that the instant claims do not integrate the judicial exception into a practical application of the exception, is not found persuasive. As an initial matter, the claims are very broadly recited and there are clearly steps missing from the process as recited in instant claim 1. One of ordinary skill in the art before the effective filing date of the claimed invention could not practically apply the invention based on the steps as recited in the instant claims (e.g., identify one or more specific peptides as having an MIC activity of <1 mM against S. aureus). In addition to missing steps (e.g., binding peptides to bacterial cells, fluorescence mission and detection, etc.), instant claim 1 does not recite a specific method of generating the library of peptides; does not provide the identity, structure, length, and/or number of peptides on the microarray; the claims do not recite the specific structure, composition, coating, features, etc. of the silicon wafer; does not recite how the library of peptides are attached to the silicon wafer; the claims do not recite the identity of the coating on the wafer and/or how it is applied; the specific photoacid generator; the identity of the suspension of cells; what they are suspended in; where the identity and location of the fluorescent labels on the bacterial cells; the method of providing a suspension; the method and/or conditions for incubating; there is no step of binding the peptides to the bacterial cells; there are no specific bacterial cells used; there is no specific level of fluorescence that is indicative of potential growth inhibition; there is no specific method of detecting fluorescence; the claims do not identify the specific method of administering; the identify candidate peptides; the amount of growth inhibition observed; whether the process comprises a reference peptide and/or reference bacterial cells; the claims do not identify the specific bacterial cells and/or the culture conditions; and/or what level of inhibition of growth of one or more bacterial cells of any genus or species is necessary to determine that a peptide is an antimicrobial peptide. For example, one of ordinary skill in the art could not immediately carry out the process as recited in instant claim 1, such that it can be determined that the peptide HfAMP has both bacteriostatic and bactericidal activity against methicillin-resistant Staphylococcus aureus at an MIC of 4mg/ml in a culture of Mueller-Hinton Broth as evidenced by Lin (entire reference). Additionally, the steps as recited in the instant claims are well known, purely conventional or routine in the art including with regard to the amino acids used, the method of producing a peptide microarray on a silicon wafer, measuring fluorescence, calculating a median signal, identifying peptides having the specific RFU, administering a candidate peptide to an array of bacterial cells, and measuring inhibition of growth of the bacterial cells. The claims as recited are merely an invitation to experiment. Thus, the claims remain rejected.
Regarding (c), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments. Applicant’s assertion that the ordered combination of steps are not well understood, routine and conventional; and none of the cited references shows routine use of the claimed threshold to select a physical candidate peptide from a synthetic peptide library lacking a known positive binder and then validate antimicrobial function in a growth assay, such that the claims recite significantly more than the judicial exception, is not found persuasive. As an initial matter, instant claim 1 does not recite:
A synthetic peptide library that lacks a known positive binder.
A step of binding one or more microarray peptides to fluorescently labeled bacterial cells, wherein such binding generates a fluorescent signal.
A step of selecting a candidate peptide.
Any specific reference peptides, reference bacterial cell suspensions and/or specific reference bacterial cell cultures.
Specific threshold values for a fluorescent signal, which is indicative of a peptide having antimicrobial activity and/or inhibitory activity against a particular species of bacterial cell.
Synthesizing and/or purifying a candidate peptide identified from the microarray.
Administering (e.g., validating) the candidate peptide in a growth assay comprising a culture of the same bacterial cells used in the binding assay, wherein growth (or inhibition of growth) is measured and compared to a reference cell suspension which was not administered the candidate peptide.
Applicant has not provided what he/she believes represents significantly more than the judicial exception and/or indicated how the claims are integrated into a practical application of the exception. Again, the steps as recited in the instant claims are well known, purely conventional or routine in the art. For example, it was known that an array of random peptide ligands including on a silicon wafer can be treated with bacterial cells and fluorescent signals measured as evidenced by Kodadek (paragraphs [0011]; [0012]; [0020]; [0054]; [0090]; [0096]; and [0100]); and it was known that antimicrobial peptides with activity against S. aureus can be tested against a suspension, wherein the AMP prevented visible growth, and minimal inhibitory concentrations were measured as evidenced by Dangel (Abstract, and pg. 4477, col 2, Microorganisms & Antimicrobial Assay). Thus, the claims remain rejected.
Claim Rejections - 35 USC § 103
The rejection of claims 1-14 is maintained under 35 U.S.C. 103 as being unpatentable over Johnston et al. (hereinafter “Johnston”) (Scientific Reports, 2017, 7(17610), 1-11; and Supplementary Information, 1-8; of record) in view of Legutki et. al. (hereinafter “Legutki”) (Nature Communications, 2014, 5(4785), 1-7; of record) as evidenced by Zlotkin et al. (hereinafter “Zlotkin”) (US Patent Application Publication 20140155318, published June 5, 2014; of record); and Sykes et al. (hereinafter “Sykes”) (US Patent Application Publication 20200064345, published February 27, 2020; of record); and Umerska et al. (hereinafter “Umerska”) (Biomolecules, 2018, 8(122), 1-13; of record).
Regarding claims 1 (in part), 2, 3 and 10-14, Johnston teaches the rapid development of new antimicrobials and the production of thousands of doses of an intervention for a new pathogen in as little as one week, wherein the feasibility of the system was tested based on antimicrobial synbodies (interpreted as identifying antimicrobial peptides, claim 1) (Abstract, lines 2-5). Johnston teaches that bacteria and viruses can be applied to peptide microarrays to generate synbodies with antibiotic or antiviral activity, where the challenge was to create a system to generate the synbodies quickly and provide sufficient quantities of the chosen synbody for in vivo testing, such that the key issue involved applying the bacterial target to 10,000 peptide microarrays (10 K), choosing and testing target peptides, synthesis of large amounts of two or more candidate peptides, synthesis of synbodies and retesting, wherein the rate-limiting step is the synthesis and purification of large amounts of the candidate peptides; and a solution to the time issue was to pre-screen a large number of pathogens on the 10K peptide microarray to arrive at 100 peptides that can offer sufficient diversity that any pathogen screened would bind two or more peptides (interpreted as a peptide array; screening bacterial cells; a target species; and interpreting a large number of pathogens as other bacterial species, claims 1, 3, 10 and 11) (pg. 2, System Overview, lines 1-9; and Figure 1A). Johnston teaches in Figures 1A and 1B that a range of pathogens (10 viruses and 11 bacteria) were screened against a library of 10,000 peptides to identify shared and specific pathogen binding peptides, wherein a total of 275 peptides were selected for secondary binding screening and down-selected for cellular toxicity, such that peptides with confirmed binding and minimal toxicity were selected for inclusion into the pathogen binding peptide microarray; and (B) workflow for discovery of antimicrobial synbodies, wherein new or unknown pathogen is fluorescently labeled and screened against the pathogen binding 100-peptide microarray, such that peptides that bind the pathogen are selected and conjugated to a synbody scaffold to produce a synbody library for activity and toxicity testing in a series of in vitro functional assays to select antimicrobial synbodies for additional development. IC stain: Intracellular staining; CW stain: Cell wall staining (interpreted as a peptide array; library of peptides including the amino acids as recited in claims 1 and 2; incubating a suspension of fluorescently labeled pathogen cells with the peptide microarray; identifying peptides bound to the labeled bacteria cells; interpreting the heatmap to provide relative fluorescence units; a target bacterial species; and other bacterial species different from the target bacterial species, claims 1-3, 10 and 11) (pg. 2, Figure 1). Figure 1 is shown below:
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Johnston teaches that the 10K array consists of 10,000 peptides spotted in duplicate on a standard size glass microscope slide with each peptide composed of 17 variable amino acids including D-amino acids and an N-terminal CSG-constant region used for immobilization to the surface, while excluding cysteine from the 17aa variable region, wherein the slide surface is coated with a polymer to increase the peptide density and to reduce non-specific binding; and the peptide of each feature is of known sequence and the variable amino acid positions in the peptide are composed of 18 different amino acids (interpreted as a peptide library comprising 15-18 amino acids as recited in claims 1 and 2) (pg. 2, Creating the 100-Peptide Microarray; last partial paragraph; pg. 7, first full paragraph, lines 1-2; and pg. 8, Peptide Microarrays, lines 5-6). Johnson teaches that when the fluorescent signal across both channels is compared, it can be seen that multiple peptides were bound to each new pathogen (Fig. 4), such that there was correlation between both fluorescent dyes and binding peptides for a new pathogen that could be easily identified including, for example, peptides with relative fluorescence values >10,000 for both fluorophores could be selected as binding peptides for the new virus; this way, multiple peptides could be selected for synbody construction, wherein these data indicate that this array can potentially identify binding peptides for any given pathogen (interpreted as identifying peptides having an RFU >10x the median fluorescence signal, claim 1) (pg. 5, first full paragraph; and Figure 4). Johnston teaches that the bacteria in the panel were screened for binding peptides in one of two ways: (1) live bacteria were screened using a previously published method; while (2) inactivated bacteria were detected using antibodies that were specific to that pathogen; and in the live bacteria screening assay, the target is labeled with an amine-reactive dye, AlexaFluor (AF), and an internalizing dye, Cell Tracker Orange (CTO), and peptides that bind the bacteria without perturbing the membrane produce fluorescence in both channels while those that disrupt the membrane only produce fluorescence in the AF channel (pg. 3, Creating the 100-Peptide Microarray; first partial paragraph). Johnston teaches in Figure 2, bacterial and viral screening against 10,000 peptide microarrays identifies common and specific pathogen binding peptides: (A) heat map of peptides (x-axis) that bound pathogens (y-axis), wherein positive peptides were defined as those with median normalized signal >2x background or >1.5x higher than the detection antibody control, such that for bacteria screened with the IC and CW labeling assay, positive peptides were positive in both fluorescent channels with a CW/IC ratio <5 (non-lytic peptides), wherein peptide intensities are colored in blue for negative and red for positive; (B) total number of peptides positive for each pathogen evaluated; and (C) graphical representation of the number of common peptides shared amongst pathogens (interpreted as identifying peptides bound to labeled bacterial cells; and relative fluorescence units encompassing at least 10 times the median signal of the fluorescence signal, claim 1) (pg. 3, Figure 2). Figure 2A-C is shown below:
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Johnston teaches in Figure 5, the relative fluorescence units (RFU) for each peptide from binding of pdm09 H1N1 (pg. 6, Figure 5). Figure 5A is shown below:
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Johnston teaches that S. epidermidis was screened against the peptide array and 20 peptides selectively bound S. epidermidis but were predicted to have low killing activity based upon their AF/CTO ratio (Fig. 6A), such that these peptides were tested by MIC and they did not inhibit S. epidermidis growth at 50 mM (not shown); then two positives binders were selected (p52 and p104) and one negative control peptide (p42) and conjugated to an S. aureus lytic peptide, called Ly, to produce a small synbody library that was then tested for inhibitory activity, wherein synbodies p42-Ly did not inhibit S. epidermidis growth at 50 mm, while p107-Ly and p104-Ly inhibited bacterial growth with MICs of 12.5 mM and 6.25 mM, respectively (Fig. 6B) (interpreted as administering peptides bound to the fluorescently labeled bacterial cells to a culture; consisting essentially of the target bacterial species; and identifying peptides the inhibit growth of the culture of bacterial cells as synthetic antimicrobial peptides, claims 1, 10 and 11) (pg. 6, Development of an Antibiotic; and Figure 6). Johnston teaches in Supplementary Table 1, microorganism strains used in the method (interpreted as a target bacterial species; consisting essentially of other bacterial species; and bacterial species of a different genus including Staphylococcus and Streptococcus, claims 1, 3, 10-12 and 14) (Supplementary Information, pg. 2):
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wherein other pathogenic bacteria include Mycobacterium abscessus, Mycobacterium avium complex, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium haemophilium, Mycobacterium kansasii, Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus epidermidis, Staphylococcus haemolyticus, etc. as evidenced by Zlotkin (paragraph [0055]); and wherein peptide arrays including arrays of at least 10,000 different peptides for the detection of a broad range of Mycobacterium including non-tuberculous mycobacterium are known in the art as evidenced by Sykes (Abstract; and paragraphs [0005]-[0006]; and [0127]). Johnston teaches bacterial growth inhibition was determined using an adapted version of the broth microdilution method in which peptides or synbodies were diluted with 1 x PBS and added in triplicate wells to bacterial suspensions of ~106 CFU/mL in Mueller-Hinton Broth (MHB) in 96-well polypropylene plate (interpreted as a suspension of fluorescently labeled bacterial cells, claim 1) (pg. 10, MIC Assay).
Regarding claim 6, Johnston teaches that infected MDCK cells were cultured for 2 days, fixed with 3% formaldehyde, and stained with 1% crystal violet (interpreting adding crystal violet as adding a metal chelator, claim 6) (pg. 9, last full paragraph, lines 6-7).
Regarding claims 8 and 9, Johnston teaches 10,000 peptides spotted in duplicate on a standard microscope slid as shown in Figure 1 below:
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peptide microarray (10K)
where a microscope slide can be arranged or selected into squares of varying sizes (interpreted as squares of 10-100 mm x 10-100 mm; and 14 mm x 14 mm, claims 8 and 9) (pg. 2, Creating the 100-peptide microarray, last partial paragraph).
Johnston does not specifically exemplify a silicon wafer and a photoacid (claim 1, in part); a non-tuberculous mycobacterium (claim 4); where the species Mycobacterium abscessus (claim 5); and EDTA (claim 7).
Regarding claim 1 (in part), Legutki teaches the production of high-density peptide arrays on silicon wafers using scalable manufacturing approaches that lend themselves to low cost and high volume, wherein the arrays have the number of features, quality of peptides and the amino acid complexity required for immunosignatures, such that the chemical identity and purity of the in situ synthesis on these arrays is characterized directly by imaging mass spectrometry, using methods we previously developed; such that these arrays can be used to generate immunosignatures that can discriminate multiple different infections and cancers from each other with statistical confidence that is as good or better than the printed arrays that have been the basis of our previous work (pg. 2, col 2, first full paragraph). Legutki teaches the synthesis of the arrays is shown schematically in Figure 3a, wherein the arrays were fabricated to specification by HealthTell, Inc. for the studies described here, such that a 520-nm thermal oxide-coated silicon wafer surface is derivatized with a monolayer of aminosilane to create peptide attachment sites, and Boc-glycine is uniformly attached to the surface, such that a photoresist containing a photoacid generator is spun on the wafer and exposed through a defined mask to 365-nm light, resulting in the patterned deprotection of Boc-protected amines in specific features on the array, wherein a coupling solution containing a Boc-protected amino acid is then spun on the wafer and coupling takes place only at the deprotected features; and the process is repeated to create the desired peptide sequence at each feature; and for the arrays described below, a distribution of peptide lengths was intentionally generated averaging 12 amino acids along with individual peptides ranging from 8 to 17 amino acids, wherein the sequence of each peptide was pseudo-randomly generated using an algorithm that minimizes the number of synthetic cycles required, and uses 16 of the 20 natural amino acids, with cysteine, methionine, isoleucine and threonine excluded, thus reducing the total number of steps to 90 lithography cycles at B20 min per cycle, such that peptide arrays are synthesized with 8-mm features and a 12-mm center-to-center spacing in an orange-crate pattern, such that the 200-mm wafers are diced into 13 75 x 25 mm slides, each with 24 identical arrays of 330,000 distinct peptides (~8 M peptides per slide), where the total assay area of each array is 0.49 cm2 (interpreted as a silicon wafer; coated with a photoresist and a photoacid generator; and an array arranged in squares of 10-100 mm x 10-100 mm; and 14 mm x 14 mm, claims 8 and 9) (pg. 5, col 2, Methods, last partial paragraph; and pg. 6, col 1, first partial paragraph).
Although the combined references of Johnston and Legutki do not specifically teach a non-tuberculous mycobacterium; and where the species Mycobacterium abscessus; Johnston does teach screening peptide arrays, cytotoxicity screens, ELISA and inhibition assays using bacteria including Escherichia coli, Staphylococcus aureus, Streptococcus mutans, etc. for the development of new antimicrobials; while Legutki does teach the production of peptide arrays useful for identifying antimicrobial peptides against pathogens such as pertussis, Lyme, and Borrelia burgdorferi, wherein other pathogenic bacteria include Mycobacterium abscessus, Mycobacterium avium complex, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium haemophilium, Mycobacterium kansasii, Staphylococcus auricularis, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus epidermidis, Staphylococcus haemolyticus, etc. as evidenced by Zlotkin; and wherein peptide arrays including arrays of at least 10,000 different peptides for the detection of a broad range of different Mycobacterium including non-tuberculous mycobacterium are known in the art as evidenced by Sykes, such that one of ordinary skill in the art would clearly recognize that peptide microarrays can be used to identify peptides bind bacterial cells including mycobacterium species such as Mycobacterium abscessus.
Although the combined references of Johnston and Legutki do not specifically teach EDTA, Johnston does teach culturing infected MDCK cells for 2 days, fixing them with formaldehyde, and staining with crystal violet, where it is known that the antibacterial activities of an antimicrobial peptide, arenicin-3 derivative AA230, and ethylenediaminetetraacetic acid (EDTA) a metal ion chelating agent in combination against Gram-negative bacteria, AA230 showed strong antibacterial activity against all of the studied standard strains and clinical isolates, while EDTA inhibited the growth of Acinetobacter baumannii as evidenced by Umerska (Abstract; and pg. 2, third full paragraph, lines 1-2), such that one of ordinary skill in the art would clearly recognize that metal ion chelators such as EDTA possess antibacterial properties.
“It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of producing high density peptide arrays as exemplified by Legutki, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the method for developing new antimicrobials including by prescreening one or more bacterial targets using a 10K peptide array, choosing and testing target peptides; selecting peptides that are somewhat pathogen-species; incubating a bacteria of interest with a 100-peptide microarray; identifying peptides that binding to it; then screening peptides bound to the bacteria that inhibit the growth of the culture of bacterial cells as disclosed by Johnston to include the method of manufacturing high-density peptide arrays on silicon wafers, wherein the array can hold >330,000 random sequence peptides in an orange-crate pattern, with a reasonable expectation of success in producing scalable high-density peptide arrays for comprehensive health monitoring via immunosignaturing including the ability to discriminate between multiple different infections at low cost and high volume; in using the high density peptide arrays and bacterial screening assays to identify and evaluate peptides for their antimicrobial activity, as well as, their potency, efficacy, and/or toxicity; and/or in directly characterizing the chemical identity and purity of the thousands of distinct peptides on the arrays by imaging mass spectrometry.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Response to Arguments
Applicants’ arguments filed July 21, 2026 have been fully considered but they are not persuasive. Applicants essentially asserts: (a) the Office Action does not articulate why a skilled artisan would have modified Johston 2’s control-based analysis to use the claimed 1-x median threshold (Applicant Remarks, pg. 9, last partial paragraph through pg. 10, first partial paragraph); (b) the record also does not establish a reasonable expectation that the claimed 10-times median threshold would distinguish candidate binders in a synthetic peptide library lacking a known positive binder, much less that candidates selected using that threshold would inhibit bacterial growth in the subsequent validation assay (Applicant Remarks, pg. 10, second full paragraph); and (c) KSR permits the use of common sense, but it does not permit hindsight reconstruction of the claimed method (Applicant Remarks, pg. 10, second full paragraph, lines 7-8)
Regarding (a) and (b), please see the discussion supra regarding the steps that appear to be missing in instant claim 1 including binding, the emission of a fluorescence signal, selecting, how a the median fluorescence signal is determined, etc. Applicant assertion that the Office Action does not articulate why a skilled artisan would have modified Johston 2’s control-based analysis to use the claimed 10x median threshold; and the record also does not establish a reasonable expectation that the claimed 10-times median threshold would distinguish candidate binders in a synthetic peptide library lacking a known positive binder, much less that candidates selected using that threshold would inhibit bacterial growth in the subsequent validation assay, is not found persuasive. MPEP 2144(I) recites:
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); Ex parte Clapp, 227 USPQ 972 (Bd. Pat. App. & Inter. 1985) (examiner must present convincing line of reasoning supporting rejection); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning) (underline added).
As an initial matter, Johnson already teaches RFUs >10x the median fluorescent signal, such that nothing in Johnson must be modified with regard to RFUs. Moreover, Johnson teaches:
When the fluorescent signal across both channels is compared, it can be seen that multiple peptides were bound to each new pathogen (Fig. 4), such that there was correlation between both fluorescent dyes and binding peptides for a new pathogen that could be easily identified (interpreted as identifying peptides having an RFU >10x the median fluorescence signal, claim 1) (pg. 5, first full paragraph).
For example, peptides with relative fluorescence values >10,000 for both fluorophores could be selected as binding peptides for the new virus; this way, multiple peptides could be selected for synbody construction, wherein these data indicate that this array can potentially identify binding peptides for any given pathogen (interpreted as identifying peptides having an RFU >10x the median fluorescence signal, claim 1) (pg. 5, first full paragraph).
A pathogen of interest is applied to the microarray and peptides selected based on the relative fluorescence (interpreted as identifying peptides having an RFU >10x the median fluorescence signal, claim 1) (pg. 5, second full paragraph, lines 1-3).
The Examiner notes that the Office Action mailed January 23, 2026 (and, supra) clearly provides a reason to combine the cited prior art references. The Applicants are reminded that the motivation for combining the teachings of the prior art may be different from applicants’ motivation to make the disclosed compositions. The fact that applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). The Office has provided motivation for modifying the method for developing new antimicrobials including by prescreening one or more bacterial targets using a 10K peptide array as disclosed by Johnson to include the high-density peptide arrays on silicon wafers, wherein the array can hold >330,000 random sequence peptides in an orange-crate pattern as taught by Legutki with a reasonable expectation of success including to produce scalable high-density peptide arrays for comprehensive health monitoring via immunosignaturing; as well as, in using the high density peptide arrays and bacterial screening assays to identify and evaluate peptides for their antimicrobial activity, as well as, their potency, efficacy, and/or toxicity;. Thus, the claims remain rejected.
Regarding (c), it is unclear to the Examiner whether Applicant is asserting that the Office has used hindsight reasoning. In response to Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Thus, the claims remain rejected.
Double Patenting
The rejection of claims 1-14 is maintained on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending US Patent No. 11752195 for the reasons of record.
Response to Arguments
Applicants’ arguments filed July 21, 2026 have been fully considered but they are not persuasive. Applicants essentially asserts: (a) Applicant requested that the Double Patenting Rejection be held in abeyance (Applicant Remarks, pg. 10, last partial paragraph through pg. 11, first partial paragraph).
Regarding (a), Applicant did not specifically indicate how the claims of the copending applications recited supra are patentably distinct from the instant claims as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
Conclusion
Claims 1-14 are rejected.
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.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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