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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4 March, 2026 has been entered.
Election/Restrictions
Applicants elected the compounds of formula I with traverse in the reply filed on 17 Sept, 2024. The traversal was found unpersuasive, and the election/restriction requirement made final in the office action of 7 Oct, 2024.
Claims Status
Claims 173-190 are pending.
Claims 174-185, 187, and 188 have been withdrawn from consideration due to an election/restriction requirement.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 173, 186, 189, and 190 are rejected under 35 U.S.C. 103 as being unpatentable over Bolt et al (MedChemComm (2016) 7 p799-805, cited by applicants) in view of Molchanova et al (ChemMedChem (2017) 12 p312-318, cited by applicants).
Bold et al discuss peptoids with antileishmanial activity (title). Among the peptoids examined is (NLysNpcbNbcp)2-4 (table 1, p803, top of page), which are identical to formula 1 with X=Cl and n=2-4 except that there are two p-chloro-N-phenylmethylene groups instead of one. Note that these are some of the only compounds with activity against amastigotes (table 1, p803, top of page), which makes them reasonable candidates for further development.
The difference between this reference and the instant claims is that this reference has less Lys analog than applicants have claimed.
Molchanova et al look at lysine based peptide/peptoid compounds for antimicrobial activity (title). The most extensively studied series is one with a Lys residue attached to a possibly substituted phenylalanine peptoid variant, i.e. a repeating unit of one lysine and one substituted phenylalanine peptoid equivalent (fig 1, p313, 2nd column, top of page). Note that many of these variants, esp those with a p-halogen phenylalanine equivalent, have reasonable antimicrobial activity and do not lyse erythrocytes (table 1, p314, top of page). Among the bacteria tested is S. aureus, as well as a methicillin resistant staph species (p313, 2nd column, 3d paragraph). This reference shows compounds similar to those of Bolt et al, but with alternating aminoalkyl and phenyl groups.
Therefore, it would be obvious to use alternating aminoalkyl and chlorophenyl groups in the peptoids of Bolt et al, as Molchanova et al show that similar compounds are active, and require high concentrations for hemolysis. As the structures of the compounds of Molchanova et al and Bolt et al are similar, and are used for the same purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
Bolt et al discusses compounds very similar to what applicants have claimed, while Molchanova et al render obvious increasing the frequency of the aminoalkyl groups, both as antimicrobial peptoids. Thus, the combination of references renders obvious claims 173 and 186.
Both Bolt et al and Molchanova et al discuss antimicrobial properties of their compounds, and Molchanova et al explicitly state that they have activity against S. aureus. Thus, the combination of references renders obvious claim 189.
While neither reference discusses methicillin resistant S. aureus or S epidermidis, the compounds showed activity against another staph species that was methicillin resistant. This shows that the resistance to methicillin does not interfere with activity, so a person of skill in the art would reasonably assume these compounds have activity against the bacteria of claim 190.
response to applicant’s arguments
Applicants argue that the difference in target microorganism between Bolt et al and Molchanova et al, that Bolt et al teaches structural requirements as necessary that are violated by the combination, that moving from a peptoid to a peptide/peptoid combination would be expected to cause the material to be ineffective, that antimicrobial design is notoriously unpredictable, that changing the halogen would be unpredictable, that adding chloro groups would be expected to increase toxicity, that increasing hydrophobicity would increase toxicity, that the research group that produced the primary reference, despite having access to the same data used in the rejection, did not come up with the claimed sequences, and that adding chlorophenyl residues would be expected to make a less active sequence.
Applicant's arguments filed 4 March, 2026 have been fully considered but they are not persuasive.
Applicants argue that the target microorganisms of Bolt et al and Molchanova et al are so different that the combination is not reasonable. However, the evidence provided is lacking. There is no explanation as to why a person of skill in the art would expect similar structures to that of Bolt et al to be ineffective against microorganisms (even though the compounds of Molchanova et al are chemically similar) or how the differences between the different compounds are responsible for their activity (and how those differences do not apply to the other microorganism). In essence, applicants are pointing to differences between the two references and stating this makes the rejection improper.
Applicants argue that a specific repeating pattern of the compounds of Bolt et al is shown to be necessary for activity, which is violated by the combination. Applicants point to no statement in this reference to support this argument, merely conclusions they make based on the data of the reference. But this is a sweeping statement based on an experiment that does not appear to be designed to show such effects. Almost all of the compounds listed have a repeating pattern of a cationic residue followed by two residues that are either hydrophobic aromatic compounds or alkyl compounds. The exceptions are block polymers where only a section follows that repeating pattern, the other section is a repeating pattern of three residues with either an aromatic or alkyl peptoid unit (both of which had good activity). That is not enough data to show that a cationic-hydrophobic-hydrophobic pattern is necessary.
Applicants argue that moving from a peptoid to a peptide/peptoid hybrid would be expected to change the properties of the combined sequence detrimentally. The only evidence that applicants have presented to support this argument is a paper showing that changing other properties can yield compounds with unpredictable activity. Note that converting a peptide to a peptoid over at least part of the structure is taught in the art as a method to improve metabolic stability (Mojsoska et al (Pharmacet. (2015) 8 p366-415, p367, 2nd paragraph).
Applicants argue that designing antimicrobial compounds is notoriously difficult, an argument that there is no reasonable expectation of success. This is, in essence, an argument that obviousness does not apply to this field; only anticipation. The courts have ruled that arguments that a field is unpredictable is not sufficient to render a rejection invalid, that obviousness is not confined to predictable arts (MPEP 2145(X)(E)). Note that applicants have made several arguments that changing specific parameters would be expected to be non-beneficial; this suggests a level of predictability that contradicts this argument.
Applicants argue that changing the halogen would be unpredictable. It is not clear what applicants are arguing; the halogen of Bolt et al is not changed.
Applicants have argued that increasing hydrophobicity and adding more chloro groups would increase toxicity, and adding more chloro groups would be expected to make the compound less active. It is not clear what applicants are arguing, the combination does not make the starting compounds more hydrophobic or add more chloro groups.
Finally, applicants argue that the research group that produced Bolt et al, despite having access to the same information, did not arrive at the claimed sequences. This argument assumes that the group behind Bolt et al has the resources to pursue all possible options. Applicants have not provided evidence that such is the case, nor does it seem likely.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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