US2019144510A1PendingUtilityA1
Modified antimicrobial peptide derived from an arginine-rich domain
Est. expiryMay 27, 2036(~9.8 yrs left)· nominal 20-yr term from priority
A61P 31/04C07K 2319/00C12N 2730/10122C12N 2730/10133C07K 14/005A01N 37/46A61K 38/00C07K 7/08C12N 2730/10033C12N 2730/10031C07K 14/02A61K 38/162A61K 38/04A01N 63/40A01N 63/50
40
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
An antimicrobial peptide, the peptide comprising 2 to 20 variable domains, each variable domain is a sequence of 2 to 20 consecutive basic amino acids, wherein (a) the variable domains are separated from each other by a variable linker, (b) the variable linker can have 1 to 20 any amino acids other than two or more consecutive basic amino acids, and (c) the peptide has no more than 100 amino acids.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . An antimicrobial peptide, the peptide comprising 2 to 20 variable domains, each variable domain is a sequence of 2 to 20 consecutive basic amino acids, wherein (a) the variable domains are separated from each other by a variable linker, (b) the variable linker can have 1 to 20 any amino acids other than two or more consecutive basic amino acids, and (c) the peptide has no more than 100 amino acids.
2 . The antimicrobial peptide of claim 1 , wherein the peptide has at least 3 variable domains.
3 . The antimicrobial peptide of claim 1 , wherein the peptide has a C-terminal cysteine.
4 . The antimicrobial peptide of claim 1 , wherein at least one of the basic amino acids in the variable domains is an arginine.
5 . The antimicrobial peptide of claim 4 , wherein all of the basic amino acids in each variable domain are arginine residues.
6 . The antimicrobial peptide of claim 1 , wherein at least one of the basic amino acids is a chemically-modified amino acid.
7 . The antimicrobial peptide of claim 6 , wherein the chemically-modified amino acid is a D-amino acid.
8 . The antimicrobial peptide of claim 7 , wherein the D-amino acid is D-arginine.
9 . The antimicrobial peptide of any of claims 1 - 8 , wherein the variable domains and the variable linkers are derived from the arginine-rich domain of a hepadnavirus core protein (HBcARD).
10 . The antimicrobial peptide of claim 9 , wherein the HBcARD contains a sequence from residue 147 to the C-terminal residue of a hepadnavirus core protein.
11 . The antimicrobial peptide of claim 10 , wherein each variable domain has three or four arginine residues and each variable linker has 2 to 4 amino acids.
12 . The peptide of claim 11 , wherein the peptide contains a consensus sequence selected from the group consisting of:
(i) (X 1 )GRX 2 P(X 3 )X 4 PX 5 P(X 6 )X 7 QX 8 P(X 9 ), wherein each of X 1 , X 3 , X 6 , and X 9 , individually, is a variable domain, and each of X 2 , X 4 , X 5 , X 7 , and X 8 , individually, is any amino acid or absent, (ii) (X 1 )GRX 2 P(X 3 )X 4 PX 5 P(X 6 ), wherein each of X 1 , X 3 , and X 6 , individually, is a variable domain, and each of X 2 , X 4 , and X 5 , individually, is any amino acid or absent, and (iii) (X 1 )X 2 PX 3 P(X 4 X 5 QX 6 P(X 7 ), wherein each of X 1 , X 4 , and X 7 , individually, is a variable domain, and each of X 2 , X 3 , X 5 , and X 6 , individually, is any amino acid or absent,
13 . The antimicrobial peptide of claim 12 , wherein the peptide has a C-terminal cysteine.
14 . The antimicrobial peptide of claim 12 , wherein the peptide has a consensus sequence selected from the group consisting of:
(i) (X 1 )GRX 2 P(X 3 )X 4 PX 5 P(X 6 )X 7 QX 8 P(X 9 )X 10 C, and (ii) (X 1 )GRX 2 P(X 3 )X 4 PX 5 P(X 6 )X 7 QX 8 P(X 9 )X 10 Q,
wherein each of X 1 , X 3 , X 6 , and X 9 , individually, is a variable domain, and each of X 2 , X 4 , X 5 , X 7 , X 8 , and X 10 , individually, is any amino acid or absent.
15 . The antimicrobial peptide of claim 12 , wherein the peptide contains a sequence selected from the group consisting of:
(i)
TVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC, in which at
least one of the arginine residues is D-arginine,
(ii)
RRRGRSPRRRTPSPRRRRSQSPRRRRSC,
(iii)
RRRGRSPRRRTPSPRRRRSQSPRRRRSQ,
(iv)
RRRGRPRRRPPRRRRQPRRRRC,
(v)
RRRGRSPRRRTPSPRRRRC,
(vi)
RRRGRPRRRPPRRRRC,
(vii)
RRRTPSPRRRRSQSPRRRRC,
or
(viii)
RRRPPRRRRQPRRRRC.
16 . The antimicrobial peptide of claim 15 , wherein the peptide contains the sequence of RRRGRSPRRRTPSPRRRRSQSPRRRRSC, in which each of the arginine residues in the sequence is L-arginine.
17 . The antimicrobial peptide of claim 15 , wherein the peptide contains the sequence of RRRGRSPRRRTPSPRRRRSQSPRRRRSC, in which at least one of the arginine residues in the sequence is D-arginine.
18 . The antimicrobial peptide of claim 17 , wherein each of the arginine residues in the sequence is D-arginine.
19 . The antimicrobial peptide of claim 17 , wherein the sequence is rRrGRSPrRrTPSPrRrRSQSPrRrRSC, in which R is L-arginine and r is D-arginine.
20 . The antimicrobial peptide of claim 17 , wherein the sequence is RrRGRSPRrRTPSPRrRrSQSPRrRrSC, in which R is L-arginine and r is D-arginine.
21 . The antimicrobial peptide of claim 15 , wherein the peptide contains the sequence of RRRGRPRRRPPRRRRQPRRRRC, in which at least one of the arginine residues in the sequence is D-arginine.
22 . The antimicrobial peptide of claim 15 , wherein the sequence is rRrGRPrRrPPrRrRQPrRrRC, in which R is L-arginine and r is D-arginine.
23 . The antimicrobial peptide of any of claims 15 - 22 , wherein the sequence is at the C-terminus of the peptide.
24 . The antimicrobial peptide of any of claims 1 - 23 , further comprising a non-HBcARD peptide.
25 . The antimicrobial peptide of claim 24 , wherein the non-HBcARD peptide is an affinity tag, a signal sequence, a ligand, or another antimicrobial peptide or fragment thereof.
26 . The antimicrobial peptide of claim 25 , wherein the non-HBcARD peptide is a poly-histidine or an analog thereof.
27 . The antimicrobial peptide of claim 26 , wherein the peptide has a sequence selected from the group consisting of:
(i)
RRRGRSPRRRTPSPRRRRSQSPRRRRSHHHHHH,
(ii)
HHHHHHRRRGRSPRRRTPSPRRRRSQSPRRRRS,
(iii)
RRRGRPRRRPPRRRRQPRRRRHHHHHH,
and
(iv)
HHHHHHRRRGRPRRRPPRRRRQPRRRR
28 . The antimicrobial peptide of any of claims 1 - 4 , wherein at least one variable domain has a lysine.
29 . The antimicrobial peptide of any of claims 1 - 4 , wherein at least one variable domain has a histidine.
30 . The peptide of any of claims 1 - 29 , wherein the peptide has a cyclic structure.
31 . The antimicrobial peptide of any of claims 1 - 30 , wherein the peptide exhibits a broad spectrum antimicrobial activity against a gram-positive bacteria, gram-negative bacteria, fungus, parasite, or virus.
32 . An antimicrobial peptide conjugate, the conjugate comprising the peptide of any of claims 1 - 31 and a non-peptide moiety.
33 . A pharmaceutical composition comprising the antimicrobial peptide of any of claims 1 - 31 and a pharmaceutically acceptable carrier.
34 . A pharmaceutical composition comprising the antimicrobial peptide conjugate of claim 32 and a pharmaceutically acceptable carrier.
35 . A method of treating a microbial infection, the method comprising administering the composition of claim 33 or 34 to a subject in need thereof.Join the waitlist — get patent alerts
Track US2019144510A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.