DETAILED ACTION
Notice of 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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Withdrawal Objections and Rejections
Applicant's response, filed 06/05/2026, has been fully considered.
In view of the amendment and remarks from 06/05/2026, the rejections of the following claims are withdrawn:
claims 1-2 and 4-8 under 35 USC § 112(a)
claims 1-2 and 4-8 under 35 USC § 103
The following rejections and/or objections are either maintained or newly applied for claims 1-2 and 4-8. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Non-Final Rejection of 04/01/2026.
Status of the Claims
Claim 3 is cancelled.
Claims 1-2 and 4-8 are pending.
Claims 1-2 and 4-8 are rejected.
Priority
This application is a CON of US Application No. 16/411,652 (05/14/2019), which claims priority from a CON of US Application No. 15/259,942 (09/08/2016), which claims priority from a CIP of PCT/US2015/019761 (03/10/2015), which claims priority from a PRO US Application No. 61/950,265 (03/10/2014), as reflected in the filing receipt mailed on 01/19/2022. However, none of the priority documents provide support for (b) determining a distribution of peptide lengths of the anti-microbial peptides within the set of anti-microbial peptides, the distribution of peptide lengths being unimodal or bimodal." Claims 1-2 and 4-8 are interpreted as being according the priority date of the effective filling date of the instant application 11/10/2021.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2 and 4-8 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kim (“Disperse Distribution of Cationic Amino Acids on Hydrophilic Surface of Helical Wheel Enhances Antimicrobial Peptide Activity” Biotechnology and Bioengineering 107(2):216-223 (2010) as cited on the 05/09/2025 Form PTO-892) in view of Pearson ("Combined bioinformatic and rational design approach to develop antimicrobial peptides against Mycobacterium tuberculosis." Antimicrobial agents and chemotherapy 60.5:2757-2764 (2016) newly cited on the attached Form PTO-892) in view of Fjell (“Designing antimicrobial peptides: form follows function” Nat. Rev. Drug Discov. (11)37-51 (2012) as cited on the 05/09/2025 Form PTO-892). The instant rejection is newly stated and is necessitated by further consideration of the claims.
Claim 1 recites:
(a) identifying a set of anti-microbial peptides having known inhibitory activity against a chosen microbe
(k) synthesizing the anti-microbial novel peptide having an alpha helical structure, one or more hydrophilic faces, and one or more hydrophobic faces including at least one hydrophobic face interruption
• Kim teaches the design and synthesis of anti-microbial peptides (AMPs) on the basis of the helical wheel structure (pg. 217 col. 2 para. 1) and a helical wheel diagram (Fig. 1 pg. 219); wherein evaluation of antimicrobial activities for seven KL model AMPs indicated one with higher antimicrobial activity against E. coli (i.e. inhibitory activity against a chosen microbe) (pg. 219 col. 1 para. 2); wherein evaluation of antimicrobial activities of KL model AMPs using the pH-controlled FRET-based assay was performed (i.e. known inhibitory activity) (Fig. 3 pg. 221); wherein at least one hydrophobic face of the one or more hydrophobic faces includes at least one hydrophobic face interruption such as KL2, KL3, KL5, KL6, and KL7; wherein the at least one hydrophobic face interruption is positioned within the at least one hydrophobic face and consists of K (Fig. 1 pg. 219);
(b) determining a distribution of peptide lengths of the anti-microbial peptides within the set of anti-microbial peptides, the distribution of peptide lengths being unimodal or bimodal
(c) selecting a mode from the distribution of peptide lengths and determining most common length of the anti-microbial peptides for the selected mode; wherein the most common length of the anti-microbial peptides for the selected mode is between 11-15 amino acids or between 24-28 amino acids
• Kim does not teach the recitation above. However, Pearson teaches wherein the peptide length of the database peptides shows a bimodal distribution centered around 9 and 25 residues where the chosen selected length for the designed anti-microbial peptides was 13 residues, the mean of the entire distribution (pg. 2759 Fig. 1).
(d) determining most common net charge of the anti-microbial peptides within the set
(e) determining most common range of hydrophobicity of the anti-microbial peptides
within the set
(f) determining most common amino acids of the anti-microbial peptides within the set
• Kim teaches the search of the APD1 database with criteria specifying similar properties as KL model AMPs: 140-180° of hydrophobic arc, +4 to +6 of net charge, and 16–25 residue length (pg. 221 col. 2 para. 1); wherein findings suggest that there are common physicochemical features shared by AMPs (i.e. reading on most common range of hydrophobicity and most common net charge) (pg. 45 col. 1 para. 3); wherein the more cationic an amino acid is the higher antimicrobial effect it has (i.e. determining most common amino acids of the anti-microbial peptides within the set) (pg. 221 col. 2 para. 1).
(g) designing an amino acid sequence by selecting amino acids of the novel peptide using a helical wheel diagram, wherein the novel peptide has the most common length determined in step (c), has the most common net charge determined in step (d), has the most common hydrophobicity determined in step ( e), consists of the most common amino acids determined in step (f), wherein the amino acid sequence forms an anti-microbial novel peptide having one or more hydrophobic faces and one or more hydrophilic faces as predicted by the helical wheel diagram, wherein at least one hydrophobic face of the one or more hydrophobic faces includes at least one hydrophobic face interruption, wherein the at least one hydrophobic face interruption is positioned within the at least one hydrophobic face and consists of one or two amino acids selected from the group consisting of K, R, H, S, T, N, Q, and combinations thereof
• Kim teaches a wheel diagram depicting peptides with one or more hydrophobic faces shown by the repeated L residues and one or more hydrophilic faces shown by the repeated K residues such as KL1, KL2, KL3, KL5, KL6, KL7, CRAMP18, CRAMP18-and CRAMP18-2; wherein at least one hydrophobic face of the one or more hydrophobic faces includes at least one hydrophobic face interruption such as KL2, KL3, KL5, KL6, and KL7; wherein the at least one hydrophobic face interruption is positioned within the at least one hydrophobic face and consists of K (Fig. 1 pg. 219).
(h) employing a software program to generate a three dimensional model of the novel peptide having the amino acid sequence designed in step (g);
(i) confirming that the three dimensional model of the novel peptide generated in step (h) has an alpha helical structure;
j) confirming that the three dimensional model of the novel peptide generated in step (h) has the one or more hydrophobic faces and the one or more hydrophilic faces, wherein steps (i) and j) are performed sequentially, non-sequentially, or simultaneously
• Kim teaches an structure–activity relationship based analyses of α-helical KL model AMPs displaying different cationic distributions and proposes that helicity and dispersity of cationic amino acids on the hydrophilic surface is a factor that contributes to the antimicrobial activity of AMPs (pg. 216 col.1); which addresses the necessity to confirm helicity, hydrophobicity and hydrophilicity properties of the AMPs in steps (h) to (j).
• Kim does not explicitly teach the use of a software program to generate a three dimensional model and confirm the recited aspects of the designed anti- microbial peptides. However, Fjell teaches the representation of three-dimensional structures of anti-microbial peptides in the membrane bilayer model using the NAMD software (Fig. 1 pg. 39).
Claim 2 recites:
wherein the amino acid sequence of the novel peptide has a cationic amino acid at least one terminus
• Kim teaches a wheel diagram depicting peptides labeled with a number representation for each residue; wherein the representation is used to identify residues in all AMPs depicted; wherein AMPs KL1, KL2, KL3, KL4, KL5, KL6, and KL7 have a cationic amino acid in one terminus; wherein the termini are depicted in positions 1 and 18 (Fig. 1 pg. 219).
Claim 4 recites:
further comprising testing the novel peptide for anti-microbial properties
• Kim teaches the evaluation of antimicrobial activities of KL model AMPs using the pH-controlled FRET-based assay (Fig. 3 pg. 221)
Claim 5 recites:
wherein the most common length of the antimicrobial peptides for the selected mode is 13 amino acids
Claim 7 recites:
wherein the most common length of the anti-microbial peptides for the selected mode is between 11-15 amino acids
• Kim does not teach the recitation above. However, Pearson teaches wherein the peptide length of the database peptides shows a bimodal distribution centered around 9 and 25 residues where the chosen selected length for the designed anti-microbial peptides was 13 residues, the mean of the entire distribution (i.e. as in claims 5 and 7) (pg. 2759 Fig. 1).
Claim 6 recites:
wherein the most common length of the antimicrobial peptides for the selected mode is 26 amino acids
Claim 8 recites:
wherein the most common length of the anti-microbial peptides for the selected mode is between 24-28 amino acids
• Kim teaches the search of the APD1 database with criteria specifying similar properties as KL model AMPs: 140-180° of hydrophobic arc, +4 to +6 of net charge, and 16–25 residue length (i.e. overlapping range between 24-28 amino acids as in claims 6 and 8) (pg. 221 col. 2 para. 1); wherein findings suggest that there are common physicochemical features shared by AMPs (pg. 45 col. 1 para. 3).
Kim teaches peptide >12 residues which makes obvious the instantly claimed range of 11-15 amino acids. Kim teaches 16-25 residues range which makes obvious the instantly claimed range of 24-28 amino acids. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05
Rationale for combining (MPEP §2142-2143)
Regarding claims 1-2 and 4-8, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Kim in view of Fjell and Pearson because all references disclose methods for the design of amino acids with antimicrobial activity. The motivation would have been to:
• boost the discovery of next-generation therapeutic peptides and peptide mimetics as anti-infectives not only for targeting bacteria that have become resistant to existing antibiotics but also for targeting disease-causing protozoa, helminths, insects and fungi (pg. 48 col. 2 para. 2 Fjell) and
• enable the design of highly selective and potent anti-microbial peptides against a specific microbial target (pg. 2763 col. 1 para. 2 Pearson).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the allelic imbalance analysis method of Kim to the methods by Fjell and Pearson because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the design of amino acids with antimicrobial activity.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 103
The Remarks of 06/05/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 5 para. 1:
According to the office action, pp. 6 and 7, Kim teaches "the search of the APDl database with criteria specifying ... residue length ... wherein findings suggest that there are common physicochemical features shared by AMPs (i.e. reading on most common length within the recited ranges). According to the office action, page 7 (referencing pg. 44, Box 1 of Fjell), Fjell's teachings include selecting a mode from the one or more modes of the distribution and determining most common length of the anti-microbial peptides for the selected mode which is accomplished by "determining a solution using the landscape distribution." Applicant respectfully submits that Kim nowhere discloses or suggests selecting a most common length within the recited ranges. Applicant further submits that the "mode" of claim 1 clearly refers to "a mode from the distribution of peptide lengths" as set forth in claim 1, whereas the mode described in the partial quote in the office action from Box 1 of Fjell refers to a mode of a multimodal fitness function of an evolutionary algorithm, wherein "the fitness landscape is either provided by determination of candidate peptides using actual biochemical activity, or by computing a structure-activity landscape." According to the wording of Box 1, these fitness modes are found for peptides " .. , containing An peptides (where A is the number of different building blocks, and n is the peptide length) . .. " This interpretation is further supported by the graph shown in Fig. 4 of Fjell, which shows that the fitness modes are in fact determined for a group of peptides having a defined length n. No combination of Fjell and Kim discloses or suggests selecting a mode from the distribution of peptide lengths and determining a most common length of the anti-microbial peptides for the selected mode. For at least this reason, an obviousness rejection of claim 1 based on Fjell and Kim would be improper. For the same reason, claims 2 and 4-8, which depend from claim 1, are non-obvious based on any combination of Fjell and Kim.
It is respectfully submitted that this is persuasive because the Examiner agrees that, in the previous office action, "Fjell's teachings include selecting a mode from the one or more modes of the distribution and determining most common length of the anti-microbial peptides for the selected mode which is accomplished by "determining a solution using the landscape distribution." The Examiner notes that a newly cited art – Pearson – has been included in this instant examination to address the argued "a mode from the distribution of peptide lengths" (i.e. claim 1 steps b-c). The prima facie case of obviousness has been established. MPEP 2141.III for "RATIONALES TO SUPPORT REJECTIONS UNDER 35 U.S.C. 103"; wherein "(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention." Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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