DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on April 20, 2026, is acknowledged.
Applicant's election with traverse of the species WKKIKKIIKKIKKI (SEQ ID NO: 12) in the reply filed on August 3, 2026, is acknowledged.
The traversal is on the ground(s) that the cited reference Benincasa et al. (NPL 1, IDS 05/24/2023) fails to disclose the subject matter of now amended claim 1. This is not found persuasive because although Benincasa et al. fails to teach a peptide with an N-terminal tryptophan residue, the amended claim motif WBBHBBHHBBH is taught by the prior art of STECKBECK (WO 2018/160997 A1). STECKBECK teaches the antimicrobial peptide (pp. 35 and 51, peptide (vii)): RRWWRRWRRWWRRWWRWWRRWWRR, which comprises the claimed sequence WBBHBBHHBBH (underlined), wherein W is tryptophan, B is the positively charged residue arginine, and H is the hydrophobic residue tryptophan. See anticipation rejection below for more details.
The requirement is still deemed proper and is therefore made FINAL.
Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elected species was searched and found to be free of the prior art. The search was extended and prior art was found that reads on claims 1, 3-7, and 9-11. The search was not extended further in accordance with MPEP § 803.02.
Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The legend for FIG. 1A states that lysine is colored in blue. However, there is no copy of a drawing in color or a petition.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3, which depends from claim 1, requires that the positively charged amino acid residues form at least three positively charged clusters each having at least two positively charged amino acid residues. However, all of the peptides of claim 1 contain the sequence WBBHBBHHBBH, wherein W is tryptophan, B is a positively charged residue, and H is an hydrophobic residue. Therefore, all of the peptides of claim contain three positively charged clusters having at least two positively charged amino acid residues (underlined). As a result, claim 3 fails to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 3-7, and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STECKBECK (WO 2018/160997 A1).
STECKBECK teaches the antimicrobial peptide (pp. 35 and 51, peptide (vii)):
RRWWRRWRRWWRRWWRWWRRWWRR
which comprises the claimed sequence WBBHBBHHBBH (underlined), wherein W is tryptophan, B is the positively charged residue arginine, and H is the hydrophobic residue tryptophan. STECKBECK is silent regarding the spatial distribution of the positively charged residues in an a-helical conformation of the peptide. Using a helical wheel program online at www.bioinformatics.nl/cgi-bin/emboss/pepwheel, the spatial distribution for the peptide is estimated as:
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306
304
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. The modeled helical wheel shows more than 150 degrees of space occupied by positively charged amino acids. This is consistent with the teaching in STEINBECK that the peptides are alpha-helical peptides with localization of positively-charged moieties on a face of the helix and localizing polar and nonpolar residues on opposing faces of the helix ([0040]-[0042]) and that this structure contributes to antimicrobial activity ([0045]-[0046], [0070]-[0072]).
Therefore, STECKBECK anticipates claim 1.
Regarding claim 3, the antimicrobial peptide RRWWRRWRRWWRRWWRWWRRWWRR contains six positively charged clusters each having at least two positively charged amino acid residues (underlined), which falls within the claimed range of at least three.
Regarding claim 4, the antimicrobial peptide RRWWRRWRRWWRRWWRWWRRWWRR contains 13 positively charged residues (underlined) out of 24 residues total, 54% positively charged amino acid residues, which falls within the claimed range of at least 50%.
Regarding claim 5, the antimicrobial peptide RRWWRRWRRWWRRWWRWWRRWWRR contains arginine as the positively charged residue.
Regarding claim 6, the antimicrobial peptide RRWWRRWRRWWRRWWRWWRRWWRR contains tryptophan as the hydrophobic residue.
Regarding claim 7, STEINBECK teaches that the antimicrobial peptide may comprise at least one D-amino acid residue ([0085])
Regarding claims 9-10, STEINBECK teaches that the antimicrobial peptide may comprise a modification in which the N-terminal amino group is acylated RC(O)- wherein R is H, alkyl, cycloalkyl, aryl etc. ([0102])
Regarding claim 11, STEINBECK teaches that the antimicrobial peptides may be included in a pharmaceutical composition ([0180]).
Allowable Subject Matter
A peptide with antimicrobial activity comprising or consisting of the amino acid sequence of SEQ ID NO: 12, and analogues thereof wherein at least one residue is in its D-form, and analogues thereof comprising an N-terminal modification group of claim 10 is allowable over the prior art.
The following is a statement of reasons for the indication of allowable subject matter:
GONG (Hydrophobic Control of the Bioactivity and Cytotoxicity of de Novo-Designed Antimicrobial Peptides. ACS Appl. Mater. Interfaces 25 September 2019; 11 (38): 34609-34620) teaches designed antimicrobial peptides (AMPs) having the following sequences (Table 1):
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118
275
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Peptide A1 of GONG is closely related to instant SEQ ID NO: 12:
SEQ ID NO: 12 WKKIKKIIKKIIKI
A1 KIKKIIKKIIKI
The difference between instant SEQ ID NO: 12 and the prior art A1 peptides is the presence of a WK dipeptide at the N-terminus. It is known in the prior art that tryptophan has a high affinity for the interfacial region of biological membranes and potentiates the interaction of Trp-containing peptides with membrane surfaces, including in antimicrobial peptides (see multiple references cited below). Although it might be obvious to modify A1 of GONG with an N-terminal tryptophan, there is no teaching, suggestion, or motivation to modify A1 of GONG with an N-terminal WK dipeptide. To do so would constitute hindsight reasoning.
CHEN (EP 2735570 B1) teaches multiple AMPs, one of which has an N-terminal WK motif:
WKKLKKLFSKLWNFK (PL-31, SEQ ID NO: 11 in Table 2).
There is no reason to modify the A1 peptide of GONG with an N-terminal WK dipeptide, such as that in peptide PL-31 of CHEN. To do so would require picking and choosing PL-31, or its D-enantiomer PL-42, from among the numerous peptides taught by CHEN all of which lack the WK dipeptide, and appending its N-terminal two residues, but no others, to A1 of GONG. There is no reason in the cited art to do so. Therefore, making this modification would constitute hindsight reasoning.
For these reasons, instant SEQ ID NO: 12 is novel and unobvious over GONG and CHEN.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The following references disclose that tryptophan has a well-known high affinity for the interfacial region of biological membranes and potentiates the interaction of Trp-containing peptides with membrane surfaces, including in antimicrobial peptides:
Mishra et al. Tryptophan-Rich and Proline-Rich Antimicrobial Peptides. Molecules 2018, 23, 815.
Yau et al. The preference of tryptophan for membrane interfaces. Biochemistry 1998, 37, 14713–14718.
Killian et al. How proteins adapt to a membrane–water interface. Trends Biochem. Sci. 2000, 25, 429–434.
Bi et al. Antimicrobial properties and interaction of two Trp-substituted cationic antimicrobial peptides with a lipid bilayer. J. Antibiot. 2014, 67, 361–368.
Shepherd et al. Interactions of the designed antimicrobial peptide MB21 and truncated dermaseptin S3 with lipid bilayers: molecular-dynamics simulations. Biochem J. 2003 Feb 15;370(Pt 1):233-43.
Khandelia et al. Cation−π Interactions Stabilize the Structure of the Antimicrobial Peptide Indolicidin near Membranes: Molecular Dynamics Simulations. J. Phys. Chem. B 11 January 2007; 111 (1): 242–250.
The following references review and disclose antimicrobial peptide structure and function but do not disclose instant SEQ ID NO: 12:
Mant et al. De Novo Designed Amphipathic a-Helical Antimicrobial Peptides Incorporating Dab and Dap Residues on the Polar Face To Treat the Gram-Negative Pathogen, Acinetobacter baumannii. J Med Chem. 2019 Apr 11;62(7):3354-3366.
Yeaman & Yount. Mechanisms of Antimicrobial Peptide Action and Resistance. Pharmacological Reviews. 2003; 55(1): 27-55
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 8:30 am - 5 pm.
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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/Primary Examiner, Art Unit 1654
