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 02/26/2026, has been fully considered.
In view of the amendment and remarks from 02/26/2026, the objection to claim 1 and the rejection of claim 4 under 35 USC § 112(b) are withdrawn.
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 Final Rejection of 11/26/2025.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/26/2026 has been entered.
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 having one or more modes; (c) selecting a mode from the one or more modes of the distribution and determining a most common length of the anti-microbial peptides for the selected mode." 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 § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-2 and 4-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection. The instant rejection is newly stated and is necessitated by claim amendment.
Claim 1 recites “(b) determining a distribution of peptide lengths of the anti-microbial peptides within the set of anti-microbial peptides, the distribution of peptide lengths having one or more modes; (c) selecting a mode from the one or more modes of the distribution and determining a most common length of the anti-microbial peptides for the selected mode" which lacks written description under 35 U.S.C. 112(a) as there is no support from any data beyond a bimodal distribution in the database [0066]. As such, there is support for "bimodal" distribution but not for more than two modes as recited in "one or more modes." The written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. See MPEP 2163. Dependent claims are similarly rejected for not resolving the lack of support introduced by claim 1.
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)) 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. Bullet points indicate the teachings of the instant features over the prior art. Instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims.
Claim 1 recites:
(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 having one or more modes
(c) 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; 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 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 length withing the recited ranges) (pg. 45 col. 1 para. 3). Additionally, Fjell teaches evolutionary algorithms based on the iterative generation of potential solutions in peptide design, wherein the underlying fitness landscape is either provided by a determination of the candidate peptides using actual biochemical activity with the best solution in the fitness landscape containing An peptides where A is the number of different building blocks, and n is the peptide length (i.e. distribution of peptide lengths of the anti-microbial peptides within the set of anti-microbial peptides – where said distribution must have at least one mode which reads on one or more modes) (pg. 44 Box 1). Kim teaches the generation of potential solutions in peptide design, wherein the underlying fitness landscape is either provided by a determination of the candidate peptides using actual biochemical activity (i.e. 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) (pg. 44 Box 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 6 recites:
wherein the most common length of the antimicrobial peptides for the selected mode is 26 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
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). Furthermore, Fjell teaches novel peptides measured against clinical pathogens being significantly shorter (nine residues long) than any natural peptide (natural peptides can be >12 residues long, but are usually >18 residues long) (pg. 45 col. 1 para. 2) . Fjell also teaches the aminolauryl-acylated AMP sequence ALWKTLLKKVLKA (i.e., 13 residue long sequence) (i.e. overlapping range between 11-15 amino acids as in claims 5 and 7) which exhibits improved bactericidal properties and is less prone to degradation (pg. 41 col. 2 para. 4).
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 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);
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 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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET.
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/F.F.L./Examiner, Art Unit 1685
/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685
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