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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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/US2021/060808 filed 11/24/2021, which claims the benefit of the priority of US Provisional application 63/117,710 filed 11/24/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements submitted on 01/02/2024, 02/04/2025 and 08/21/2025 have been considered by the examiner.
Election/Restrictions
Claim 30 is are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II or based on the elected species, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 05/21/2026. Applicant’s election with traverse of Group I drawn to a polypeptide construct, in the reply filed on 05/21/2026 is acknowledged. The traversal is on the ground that the Groups overlap in scope. Examiner disagrees since claim 30 is a distinct claim reciting numerous sequences and the claims of group 1 are drawn to a construct comprising a polypeptide.
Applicant further elects the species of “same non-natural amino acids, (S)-2-(4’-pentenyl)alanine (S5) and SEQ ID NO: 453. As a result, claim 29 is withdrawn from consideration.
Claim Status
Claims 1-7, 9-17, 20-25, 28-30 are pending. Claims 8, 18-19, and 26-27 are canceled. Claims 29-30 are withdrawn. Claims 1-7, 9-17, 20-25, 28 are being examined on the merits in this office action.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Please see [0038] of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
The drawings are objected to because Fig. 1 is not clear. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4-7, 9-11, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Moellering et al. (US20190135868A1 – hereinafter “Moellering”).
Regarding claim 1, Moellering teaches a synthetic DNA binding domain peptide comprising a modified peptide that binds to a DNA molecule comprising an E-box transcription factor binding domain, wherein said peptide comprises a dimerization moiety configured to form a dimer with a second modified peptide (claim 1; [0008]), wherein said peptide is derived from a basic helix-loop-helix leucine-zipper (bHLH-LZ) transcription factor (claim 4; [0007, 0008), wherein the corresponding monomer stapled helix contains a C-terminal reactive dimerization moiety [0026], wherein said peptide is a monomeric peptide, and that the peptide is a dimeric peptide linked by said dimerization moiety (claims 6-7), wherein said at least one peptide comprises two peptides covalently linked by one or more dimerization moieties such as thiol-maleimide (claim 13, 17; [0013, 0026, 0036, 0142]). Fig. 23 shows the second polypeptide extends in the C-terminal direction from end of loop of the bHLH (Fig. 23).
Regarding claims 4-5, 10, Moellering teaches the stapled polypeptides comprises amino acids substituted with non-natural amino acid [0010, 0027, 0133, 0148]. Moellering teaches that the polypeptide of Fig. 7, wherein the amino acids shown in white represents non-natural amino acids (See Fig. 7). Additionally, Moellering teaches that X2 and X2° are independently modified or unnatural amino acid linked to X7 and X7°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids; and that X7 and X7° are independently any modified or unnatural amino acid linked to X2 and X2°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids, 0557, 0562]. This reads on two non-natural amino acids.
Regarding claim 6, Moellering teaches that the non-natural amino acids are conjugated via Diels Alder reaction, or via a Huisgen 1,3-dipolar cycloaddition reaction to form a homodimer or a heterodimer polypeptide [0605-0606] or via olefin metathesis (RCM) [0057, 0562].
Regarding claim 7 and 9, Moellering teaches that the non-natural amino acid is
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[0569-0572], which is identical to the instant elected species S5.
Regarding claim 11, Moellering teaches that X2 and X2° are independently modified or unnatural amino acid linked to X7 and X7°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids; and that X7 and X7° are independently any modified or unnatural amino acid linked to X2 and X2°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids, 0557, 0562]. Moellering further teaches that conjugation methods include thiol-maleimide Michael addition [0034, 0142, 0538, 0540, 0566, 0568, 0655].
Regarding claim 28, Moellering teaches that the polypeptide binds to the sequence 5′-CACGTG-3′ [0008, 0012, 0021].
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 (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.
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.
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) 2-3, 12-17, and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over Moellering et al. (US20190135868A1 – hereinafter “Moellering”) as applied to claim 1 above, and further in view of Pires et al. (Mol. Biol. Evol. 2009 Nov 25; 27(4): 862–874) and Mudd et al. (US20180236065A1).
The teachings of Moellering are disclosed above and incorporated herein by reference.
Moellering does not teach that the polypeptide extends to 36 amino acid as recited in claim 2.
Pires teaches that basic helix-loop-helix (bHLH) proteins are a class of transcription factors found throughout eukaryotic organisms. Piers teaches the sequence of the several proteins showing the basic, helix and loop which shows that the polypeptide extends 36 residues in the N-terminal direction from the start of the loop, or 31 residues in the C-terminal direction from the end of the loop of the bHLH as shown below (Fig. 2 on Page 865).
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Pires further discloses in the supplementary data the polypeptide sequence that comprises the instant SEQ ID NO: 453.
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(Page 65 of supplementary data). Pires teaches that Max homodimer bound to an E box, derived from the Adenovirus major late promoter, established the structural bases for DNA recognition by bHLHZ proteins and that basic region projects from the N-terminal face of the four-helix bundle and interacts with DNA via sequence-specifying contacts with the major groove edges of base pairs comprising the E box (Page 195, left col., 2nd paragraph).
Additionally, Mudd teaches a construct that comprises a peptidic first alpha-helix and a peptidic second alpha-helix coiled to the first alpha-helix and teaches covalent coupling [0013-0127, 0259]. Mudd further teaches two peptide strands with an alpha-helix structure which are coiled to each other, are herein referred to as a dimer and that the construct can be a tetramer having four peptides [0035].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the construct of Moellering and use the polypeptide as taught by Piers since the structure dimerizes to form an asymmetric, parallel left-handed four-helix bundle composed of two pairs of right-handed helices (Page 195, left col., 2nd paragraph). Additionally, it would have been obvious to include a third and fourth polypeptide for high affinity. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the polypeptides of Pires since they have been successful in forming a construct that demonstrated high DNA binding affinity (Page 195, right col., 1st paragraph). The disclosures render obvious claim 12.
Regarding claims 2-3 and 13-14, Pires teaches that basic helix-loop-helix (bHLH) proteins are a class of transcription factors found throughout eukaryotic organisms. Piers teaches the sequence of the several proteins showing the basic, helix and loop which shows that the polypeptide extends 36 residues in the N-terminal direction from the start of the loop, or 31 residues in the C-terminal direction from the end of the loop of the bHLH as shown below (Fig. 2 on Page 865). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the construct of Moellering and use the polypeptide as taught by Piers since the structure dimerizes to form an asymmetric, parallel left-handed four-helix bundle composed of two pairs of right-handed helices (Page 195, left col., 2nd paragraph).
Regarding claims 15-16, and 21, Moellering teaches the stapled polypeptides comprises amino acids substituted with non-natural amino acid [0010, 0027, 0133, 0148]. Moellering teaches that the polypeptide of Fig. 7, wherein the amino acids shown in white represents non-natural amino acids (See Fig. 7). Additionally, Moellering teaches that X2 and X2° are independently modified or unnatural amino acid linked to X7 and X7°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids; and that X7 and X7° are independently any modified or unnatural amino acid linked to X2 and X2°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids, 0557, 0562]. This reads on two non-natural amino acids. It would have been obvious to modify the construct of Moellering and include the third and fourth polypeptide as taught by Mudd and include non-natural amino acids.
Regarding 17, Moellering teaches that the non-natural amino acids are conjugated via Diels Alder reaction, or via a Huisgen 1,3-dipolar cycloaddition reaction to form a homodimer or a heterodimer polypeptide [0605-0606] or via olefin metathesis (RCM) [0057, 0562].
Regarding claim 20, Moellering teaches that the non-natural amino acid is
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[0569-0572], which is identical to the instant elected species S5.
Regarding claims 22-23, Moellering teaches that X2 and X2° are independently modified or unnatural amino acid linked to X7 and X7°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids; and that X7 and X7° are independently any modified or unnatural amino acid linked to X2 and X2°, respectively, via a hydrocarbon staple resulting from a ring-closing olefin metathesis (RCM) of hindered α-methyl, α-alkenyl amino acids, 0557, 0562]. Moellering further teaches that conjugation methods include thiol-maleimide Michael addition [0034, 0142, 0538, 0540, 0566, 0568, 0655]. It would have been obvious to modify the construct of Moellering and include a third and fourth polypeptide and link them via a maleimide-thiol adduct.
Regarding claims 24-25, Moellering teaches that conjugation methods include thiol-maleimide Michael addition [0034, 0142, 0538, 0540, 0566, 0568, 0655]. Moellering teaches that the conjugation on the C-terminal and that the thiol and maleimide on the C-terminal [0654, 0656]. It would have been obvious to modify the construct of Moellering and include a third and fourth polypeptide and link the second and fourth polypeptide via a maleimide-thiol adduct.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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