Patent US5574142A successfully refreshed from Google Patents.
US5574142A
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Peptide linkers for improved oligonucleotide delivery
Assignee: Epoch Biosciences Inc
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Filing: 1992-12-15
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Granted: 1996-11-12
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Expires: 2012-12-15
Abstract
Abstract A covalently linked conjugate of an oligonucleotide (ODN) with a peptide and a carrier or targeting ligand (ODN-peptide-carrier) includes a therapeutic oligonucleotide which is capable of selectively binding to a target sequence of DNA, RNA or protein inside a target cell. The ODN is covalently linked to a peptide which is capable of being cleaved by proteolytic enzymes inside the target cell. The peptide, in turn is covalently linked to a carrier or targeting ligand moiety which facilitates delivery of the entire ODN-peptide-carrier conjugate into the cell, and preferably into a specific target tissue type. Inside the cell, the peptide is cleaved, releasing the ODN which, by binding to the target DNA, RNA or protein sequence, brings about a beneficial result.
Inventors
- 👤 Rich B. Meyer, Jr.
- 👤 Alexander A. Gall
- 👤 Michael W. Reed
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 08:46
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/54; A61K47/549; A61K47/62; A61K47/64; A61K47/6889
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
133 words
An oligonucleotide-peptide-carrier conjugate wherein the oligonucleotide, peptide and carrier moieties are covalently linked to one another, and wherein: the oligonucleotide is selected from a group consisting of antisense oligonucleotide, antigene oligonucleotide, protein binding oligonucleotide and ribozyme which selectively binds to a desired sequence of RNA, DNA or protein in a target cell, and which by binding to the desired RNA, DNA or protein sequence brings about a desired therapeutic effect, the oligonucleotide optionally being modified relative to naturally occurring oligonucleotides to increase binding to the desired RNA, DNA or protein sequence or to increase resistance to nuclease enzymes; the peptide is cleavable by protease enzymes within the lysosomes of a target cell, and the carrier is a lysosomotropic carrier which is capable of facilitating transport of the oligonucleotide-peptide-carrier conjugate into the target cell.
Claim 2
Dependent Claim
133 words
An oligonucleotide-peptide-carrier conjugate wherein the oligonucleotide, peptide and carrier moieties are covalently linked to one another, and wherein: the oligonucleotide is selected from a group consisting of antisense oligonucleotide, antigene oligonucleotide, protein binding oligonucleotide and ribozyme which selectively binds to a desired sequence of RNA, DNA or protein in a target cell, and which by binding to the desired RNA, DNA or protein sequence brings about a desired therapeutic effect, the oligonucleotide optionally being modified relative to naturally occurring oligonucleotides to increase binding to the desired RNA, DNA or protein sequence or to increase resistance to nuclease enzymes; the peptide is cleavable by protease enzymes within the lysosomes of a target cell, and the carrier is a lysosomotropic carrier which is capable of facilitating transport of the oligonucleotide-peptide-carrier conjugate into the target cell.
Claim 3
Dependent Claim
13 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the oligonucleotide is an antisense oligonucleotide.
Claim 4
Dependent Claim
13 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the oligonucleotide is an antigene oligonucleotide.
Claim 5
Dependent Claim
14 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the oligonucleotide is a protein binding oligonucleotide.
Claim 6
Dependent Claim
12 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the oligonucleotide is a ribozyme.
Claim 7
Dependent Claim
34 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the peptide includes the sequence selected from the group consisting of -leu-ala-leu-ala- (Sequence ID No.: 13), gly-phe-leu-gly- (Sequence ID No.: 2) and gly-phe-tyr-ala (Sequence ID No.: 12).
Claim 8
Dependent Claim
43 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the peptide includes the sequence selected from the group consisting of H 2 N-cys-leu-ala-leu-ala-lys-CONH 2 (Sequence ID No.: 6), H 2 N-cys-gly-phe-leu-gly-lys-CONH 2 (Sequence ID No.: 7) and N 2 N-cys-gly-phe-tyr-ala-lys-CONH 2 (Sequence ID No.: 15).
Claim 9
Dependent Claim
13 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the carrier is a lipophilic group.
Claim 10
Dependent Claim
56 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the peptide is covalently linked to the 5' or 3' tail of the ODN through a covalent linkage which comprises the structure ODN-5' or 3'-O--P(O,O.sup.-)--O(CH.sub.2).sub.o --NH--CO--CH.sub.2 --S-PEPTIDE-NH-- where o is an integer beween 2 and 12, ODN represents the oligonucleotide and PEPTIDE represents the residue of the peptide moiety.
Claim 11
Dependent Claim
10 words
The oligonucleotide-peptide-carrier conjugate of claim 9 wherein o is 6.
Claim 12
Dependent Claim
42 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the peptide is covalently linked to the carrier moiety through a covalent linkage which comprises the structure -PEPTIDE-NH--CO--CH.sub.2 --S-CARRIER, wherein PEPTIDE represents the residue of the peptide, and CARRIER represents residue of the carrier moiety.
Claim 13
Dependent Claim
126 words
The oligonucleotide-peptide-carrier conjugate of claim 1 wherein the peptide is covalently linked to the 5' or the 3' tail of the ODN through a covalent linkage which comprises the structure ODN-5' or 3'-O--P(O,O.sup.-)--O(CH.sub.2).sub.o --NH--CO--CH.sub.2 --S-PEPTIDE -NH-- and wherein the peptide is covalently linked to the carrier moiety through a covalent linkage which comprises the structure -PEPTIDE-NH--CO--CH.sub.2 --S-CARRIER, or -PEPTIDE-NH--W--NH-CARRIER where o is an integer beween 2 and 12, ODN represents the oligonucleotide moiety, PEPTIDE represents the residue of the peptide moiety, CARRIER represents residue of the carrier moiety and W represents an chlorinated symmetrical triazine moiety which is obtained when a nucleophilic NH 2 group of the peptide moiety and a nucleophilic NH 2 group of the carrier moiety is bridged by reaction with cyanuric chloride.
References Cited (Backward Citations)
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