DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/16/2026 has been entered.
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 03/16/2026 are acknowledged.
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the previous rejection is maintained and modified to address claim amendments. Please see the examiners response to applicants arguments below.
Applicants are reminded that previous restriction requirement and elected species are remain same. Amended claims are still examined on merits in light of elected species.
Response to Arguments
(i) Applicants argue that Chen concludes that the specific sequence and positional arrangement of certain residues within a short peptide are critical for its antibacterial activity. Furthermore, Chen discloses that introducing an isoleucine substitution resulted in exceptional growth inhibition ability (MIC), but almost completely eliminated the direct bactericidal ability (MBC). These teachings from Chen clearly demonstrate that the introduction of a specific amino acid-such as adding a lysine at a specific terminal position-does not universally or predictably improve all, or even the desired, properties of an antibacterial peptide. Therefore, a person of ordinary skill in the art would not have had a reasonable expectation of success that adding a lysine specifically to the N-terminus of Yu's 14-residue peptide (to form a 15-residue peptide) would predictably improve or retain the desired activity.
First, Chen finds that in construction of potent antibacterial peptides, inclusion of Arg, Lys and Trp or Ile residues enhances effectiveness against certain bacteria, as measured by MIC or MBC.
Second, Chen substituted all its basic residues with arginine or lysine and other nonbasic residues with tryptophan, phenylalanine, or isoleucine to generate LFB-RW and LFB-RWa, and both peptides had a 2-fold greater activity against S aureus than bLf 20-29. Peptides LFB-RW and LFB-RWa differ only in the fifth residue, at which LFB-RWa has an arginine instead of tryptophan. This single residue did not appear to affect much of the antibacterial activity of these peptides against E coli and S aureus, but it did result in a 2-fold lower activity of LFB-RWa against E faecalis. Although introducing more tryptophan and arginine residues could enhance the antibacterial activity of short peptides, the antibacterial activity of peptides in our study did not increase much, as determined on the basis of MIC and MBC values. This finding suggests that the order (or position) of certain residues in the peptides may be critical for the antibacterial activity of short peptides.
Finally, based on the above, Chen observed amino acid modifications of antibacterial peptides may not effective for all bacteria, and also Chen did not observe any uncertainties with Lys. Moreover, Chen suggests that the order (or position) of certain residues in the peptides may be critical for the antibacterial activity of short peptides. Therefore, skilled person in the art would be motivated to incorporate desired amino acids at terminal positions, not in the middle of a peptide, and would determine suitable target bacteria through routine experimentation.
(ii) Applicants argue that by specifically loosening the outer membrane of Gram-negative bacteria, the claimed peptide enables existing antibacterial agents to pass through and exhibit activity. Simultaneously, this unique structural arrangement achieves minimized toxicity to host cells, excellent sensitizing effects even at low concentrations, and a delay in the appearance of resistant bacteria. See, e.g., paras. [0031] to [0035], [0094] to [0101] and Examples 1 to 16 of the PCT specification.
It appears that there is no shown data with elected species in the specification. Further, there is no comparative data with other variants in the specification. Accordingly, shown data is expected, absent evidence to the contrary.
(iii) Applicants argue that neither Yu, Chen, Jerala, nor Albada-alone or in combination-teaches or suggests a peptide acting as an outer-membrane loosener/potentiator rather than a traditional AMP. The simultaneous achievement of these complex objectives (reducing host toxicity while significantly enhancing the sensitizing effect) through the specific 15-amino acid arrangement (see para. [0032] and Examples 1 to 10 of the PCT specification) is remarkable and entirely unpredictable from the purported combined teachings of Yu, Chen, Jerala, and Albada.
As explained in the above response, applicants failed to show any comparative data in the specification and so, claimed modifications are obvious and the results are expected. Moreover, pending rejection explains advantages of additional amino acid, in this case Lys at X1 position. Rejection also explains advantages of bound C6 to C16 fatty acid to the peptide.
Applicant is reminded that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, the rejection relies on the combination of the references together. Applicants show how each cited reference differ from the instant invention, but the obviousness test under 35 U.S.C. 103 is whether the invention would have been obvious in view of the prior art taken as a whole. In re Metcalf et al. 157 U.S.P.Q. 423.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-13 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Yu (WO 2017/048092 A1 or its equivalent US 2018/0339016 A1) in view of Chen (AJVR, vol.64, No.9, Sep 2003, 1088-1092), Jerala (Expert Opin. Investig. Drugs, 2007, 16(8): 1159-1169) and Albada (ACS Med.Chem.Lett., 2012, 3, 980-984).
Yu teaches a peptide represented by sequence KLLKL AKKPL KLLK [see SEQ ID NO:55].
Above sequence reads applicants elected species and also X2-X15 in claimed formula 1. Please note that the recited proviso is not applicable, because elected species does not read it, and so the proviso is not considered as an additional limitation.
Differences between Yu and claims of present application are as follows:
(i) Yu is silent on applicants claimed X1 group, which is K in the elected species.
(ii) Yu is also silent on bound C6 to C16 fatty acid to the peptide.
With regard to (i) of above, incorporation of basic amino acids in antimicrobial peptides are known in the art since these amino acids, viz., K or R, are known to increase the anti-bacterial activity. For example, Chen teaches incorporation of lysine in the short hydrophobic and basic rich peptides increases antibacterial activity [see abstract]. Therefore, a skilled person in the art would be motivated to incorporate basic amino acids to increase the antibacterial activity of short peptides.
With regard to (ii) of above, lipidation of antimicrobial peptides are also known and is a common practice in the art, since it increases the activity of peptides [see review article by Jeral, Expert Opin. Investig. Drugs, 2007, 16(8):1159-1169]. In addition, Albada teaches tuning the activity of short Arg-Trp antimicrobial peptide by lipidation of a C- or N-terminal lysine side-chain with C6-C14 lipids [see abstract; 3rd paragraph in right column in page 981; Table 1]. Therefore, one would be motivated to couple the peptide with a fatty acid groups.
Based on above teachings, a skilled person in the art would be motivated to choose lysine for applicants X1 group, because it can meet two functionalities, viz., it can increases antibacterial activity and also can accommodate fatty acid.
The motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658