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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 24 Sept, 2025 has been entered.
Election/Restrictions
Applicants elected the 15 peptides on p7 of the specification without traverse in the reply filed on 5 Nov, 2022. That species was found allowable in the office action of 20 Dec, 2024.
Claims Status
Claims 114, 116, 124, 129, 130, 133-136, 140-142, and 145-152 are pending.
Claims 114 and 151 have been amended.
Claims 116, 124, 129, 130, 134-136, 142, 145, 146, 149-152 have been withdrawn due to an election/restriction requirement.
Maintained/Modified Objections
Claim Objections
Claims 147 and 148 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
New Objections
Claim Objections
Claims 147 and 148 are objected to because of the following informalities: these claims list sequences, without the appropriate SEQ ID number. The MPEP states that "37 CFR 1.821(d) requires the use of the assigned sequence identifier in all instances where the description or claims of a patent application discuss sequences regardless of whether a given sequence is also embedded in the text of the description or claims of an application” (MPEP 2422.03).
Appropriate correction is required.
Withdrawn Rejections
The rejection of claim 115 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is hereby withdrawn due to amendment.
The rejection of claims 114, 115, 117, 121, 123, 133, 140, and 141 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to how broadly to interpret the term “fatty acid” is hereby withdrawn due to amendment.
The rejection of claims 121 and 123 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to which amino acids “the hydrophobic amino acid” and “the cationic amino acid” refer to is hereby withdrawn due to amendment.
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) 114, 133, 140, and 141 are rejected under 35 U.S.C. 103 as being unpatentable over Izgu et al (J. Am. Chem. Soc. (2016) 138(3) p16669-16676) in view of Higgs et al (Astrobiol. (2009) 9(5) p483-491).
Igzu et al discuss acylation of peptides using NCAs for making membranes under pre-biotic conditions (title). Valine NCA was mixed in EPPS buffer with either oleic acid or octanoic acid and a free amino acid (p16670, 2nd column, 1st paragraph), leading to a mix of sequences of a fatty acid, a variable number of valine residues, and the amino acid (fig 1a). Among the mixtures formed was FA-(Val)0-5Arg, FA-(Val)0-5His, and FA-(Val)0-5Lys (table S1, pS3, top of page). Note that all these mixtures have sequences between 3 and 6 AAs, with zero or one cationic amino acid and 2-5 valine residues, capped with a fatty acid. Oleic acid is monounsaturated, while octanoic acid is saturated. The peptide has both valine and either Arg, His, or Lys. The formulations were made in a buffered aqueous solution with nothing clearly toxic in it. Note that, as surfactant compounds, which are antimicrobial, this reference is relevant to the problem that applicants are trying to solve.
The difference between this reference and the examined claims is that this reference uses a hydrophobic amino acid that applicants have explicitly excluded.
Higgs et al look at prebiotic amino acids (title). The hydrophobic amino acids found in non-biological contexts are Ala, Val. Ile, Leu, and Pro (table 1, p484, bottom of page). This reference discusses non-biological formation of amino acids.
Therefore, it would be obvious to use alternative hydrophobic amino acids found in a pre-biotic environment, esp. the more common ones, to see if they formed materials with similar properties to the valine compounds of Igzu et al. As the chemistry used by Igzu et al is standard NCA chemistry, an artisan in this field would attempt this process with a reasonable expectation of success.
Alternatively, differences in the number of carbons in a hydrocarbon chain is not considered a patentable distinction (MPEP 2144.09), so the Val side chain of Igzu et al is not considered patentably distinct from Ile or Leu.
response to applicant’s arguments
Applicants argue that Izgu et al generates the mixture without isolating and using it, that there is no guidance to generate the claimed conjugates.
Applicant's arguments filed 24 Sept, 2025 have been fully considered but they are not persuasive.
Applicants argue that Izgu et al does not isolate or use the material. This is not entirely correct. The reference mentions some of the components of the reaction will mediate RNA-vesicle association (p16670, 1st column, 1st paragraph). In essence, Izgu et al are looking at plausible reactions on the border of life and non-life.; the utility of the materials is to see how they interact with protocells and other biological materials, to look for possible pathways in pre-biotic systems. In addition, to identify the compounds, there has to be some sort of isolation.
Applicants argue that there is no guidance to generate the claimed conjugates. Izgu et al teach how to make the materials; as many of the amino acids are homologs or otherwise similar to those used by Izgu et al, they are presumed to generate similar materials.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 114, 133, 140, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 71-73, 76, 79, and 82 of copending Application No. 17/760,357 (US 20230076173) in view of de Almeida et al (ACS Appl. Mater. Interfaces (2019) 11 p2790-2801, available Dec, 2018).
Competing claim 71 describes an antimicrobial matrix comprising a plurality of synthetic peptides with hydrophobic and cationic amino acids in random sequence, attached to a water insoluble polymer via a linker. Competing claims 72 and 73 specify the cationic and hydrophobic amino acids similarly with the examined claims. Competing claim 76 specifies that the peptides are between 5 and 50 AA in length, within the range of the examined claims. Competing claim 79 specifies a stable covalent bond binding the polymer and the peptide to the linker, while competing claim 82 specifies the polymer from a Markush group that includes polyethylene.
The difference between the competing claims and the instant claims is that the competing claims do not specify a fatty acid.
de Almeida et al describes antimicrobial cationic and cationic/hydrophobic peptides attached to fatty acids, including C12, C16, C14, C8, C10, (table 1, p2792, top of page). Note that the fatty acids are saturated (table 1, p2792, top of page). In other words, these are polyethylene oligomers attached to the peptide by a carboxylate linker.
As de Almeida et al describes an embodiment of the polymer-linker in a similar construct (fatty acid-peptide) for the same purpose (antimicrobial), it would be obvious to use that embodiment for the matrices of the competing claims. As these peptides were mostly active (table 2, p2793, top of page), an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants request that this rejection be held in abeyance until the claims are otherwise determined to be allowable. However, until the rejection is overcome, it will remain.
New Rejections
Claim Rejections - 35 USC § 103
The legal basis for rejections under this statute was given above, and will not be repeated here.
Claim(s) 114, 133, 140, and 141 are rejected under 35 U.S.C. 103 as being unpatentable over Whittaker et al (US 5,906,922).
Whittaker et al peptides conjugated to a fatty acid and complexed to a nucleic acid (abstract). The examples use a sequence of 1-5 Lys residues attached at the C-terminus to a hydrophobic amino acid (Ala, Leu, Phe, Gly), attached at the C-terminus to a Tris residue, to which 1-3 fatty acids are attached (palmitate, myristate, laurate, or caproate) (column 15, line 1-7, column 16, line 4-7, column 17, line 6-9, and column 19, line 2-9). While varying these parameters will affect the amount an added nucleic acid is taken up by cells, almost all of the variants have some uptake ability (table 1, column 14, table 2, column 18, table 3, column 19). At least one embodiment of their invention was tested in vivo (column 25, line 63-column 26, line 34), indicating a pharmaceutical composition.
The difference between this reference and the examined claims is that, while this reference describes each of the compounds in applicant’s claimed mixture separately, they do not make a mixture of them.
However, the MPEP states that “it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. . .the idea of combining them flows logically from their having been individually taught in the prior art" (MPEP 2144.06). All these conjugates are used for the same purpose, transfection, so it is considered obvious to mix them together.
Whittaker et al renders obvious mixtures of a Lys sequence of 4 or 5 lysines, attached to a hydrophobic amino acid, attached to a fatty acid between C10 and C18, rendering obvious claim 114.
Whittaker et al discusses in vivo use, requiring a pharmaceutical formulation and rendering obvious claim 133.
Claims 140 and 141 give intended uses of the mixture. However, so long as the prior art formulation is suitable for the intended use, it reads on the claims (MPEP 2122 and 2111.02).
Examiner’s Note
Claims 147 and 148 both include the sequence KKKK attached to a fatty acid in the claimed mixture, which does not have the hydrophobic amino acid required by claim 114. However, as claim 114 has no language prohibiting additional moieties in the mixture, and the remaining sequences satisfy the claim limitation, this was not considered an issue.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kabanov et al (Prot. Eng. (1989) 3(1) p39-42). This reference discusses adding fatty acids to polypeptides to improve membrane transport. Coupled with Hayouka et al (WO2017134661), this is an alternative way to render the claims obvious.
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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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658