Compositions for detection, inhibition and imaging of indoleamine 2, 3-dioxygenase 1 (IDO1) and methods of making and using same
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsBert Tsunyin Lai, Heather Dawn Agnew
Life of this patent
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Abstract
The present application provides stable peptide-based IDO1 capture agents and methods of use as detection, imaging, diagnostic and therapeutic agents. The application further provides methods of manufacturing IDO1 imaging agents.
Claims26
A binding agent that specifically binds indoleamine 2,3-dioxygenase 1 (IDO1) comprising a first ligand having affinity for an epitope on IDO1, wherein the ligand comprises a cyclic peptide having an amino acid sequence selected from the group consisting of:
- (a) X1rf(Me-Trp)X2, wherein X1 and X2 are independently D-Ala, D-Arg, D-Asn, D-Asp, D-Glu, Gly, D-His, D-Leu, D-Lys, D-Phe, D-Pro, D-Ser, D-Thr, D-Trp, D-Tyr, or D-Val or is not present;
- (b) nsfr(Me-Trp);
- (c) wyrX3y, wherein X3 is D-Ala or is not present;
- (d) rys(Me-Trp)r;
- (e) X4lf(Me-Trp)(F-Phe), wherein X4 is D-Ala, D-Arg, D-Asn, D-Asp, D-Glu, Gly, D-His, D-Leu, D-Lys, D-Phe, D-Pro, D-Ser, D-Thr, D-Trp, D-Tyr, or D-Val or is not present;
- (f) nlw(Me-Trp)r;
- (g) sX5ww(F-Phe), wherein X5 is D-Ala, D-Arg, D-Asn, D-Asp, D-Glu, Gly, D-His, D-Leu, D-Lys, D-Phe, D-Pro, D-Ser, D-Thr, D-Trp, D-Tyr, or D-Val or is not present;
- (h) rffyl;
- and
- (i) nsh(F-Phe)r.
A binding agent that specifically binds IDO1, wherein the binding agent comprises a first ligand having affinity for a first epitope on IDO1, a second ligand having affinity for a second epitope on IDO1, and a linker covalently connecting the first ligand to the second ligand, wherein the first and second ligands each comprises a cyclic peptide,
- wherein the cyclic peptide of the first ligand has an amino acid sequence selected from one of the groups (1), (2), or (3) and wherein the cyclic peptide of the second ligand has an amino acid sequence selected from one of the two groups from which the amino acid sequence of the cyclic peptide of the first ligand was not selected,
- wherein group (1) consists of:
- (a) X1rf(Me-Trp)X2, wherein X1 and X2 are independently D-Ala, D-Arg, D-Asn, D-Asp, D-Glu, Gly, D-His, D-Leu, D-Lys, D-Phe, D-Pro, D-Ser, D-Thr, D-Trp, D-Tyr, or D-Val or is not present;
- (b) nsfr(Me-Trp);
- and
- (c) wyrX3y, wherein X3 is D-Ala or is not present, wherein group (2) consists of:
- (d) rys(Me-Trp)r;
- (e) X4lf(Me-Trp)(F-Phe), wherein X4 is D-Ala, D-Arg, D-Asn, D-Asp, D-Glu, Gly, D-His, D-Leu, D-Lys, D-Phe, D-Pro, D-Ser, D-Thr, D-Trp, D-Tyr, or D-Val or is not present;
- (f) nlw(Me-Trp)r;
- and
- (g) sX5ww(F-Phe), wherein X5 is D-Ala, D-Arg, D-Asn, D-Asp, D-Glu, Gly, D-His, D-Leu, D-Lys, D-Phe, D-Pro, D-Ser, D-Thr, D-Trp, D-Tyr, or D-Val or is not present, and
- wherein group (3) consists of:
- (h) rffyl;
- and
- (i) nsh(F-Phe)r.
A binding agent that specifically binds indoleamine 2,3-dioxygenase 1 (IDO1) produced by a method comprising
- (a) contacting an epitope of IDO1 to a library of molecules wherein each member of the library comprise distinct cyclic peptides of 5-10 amino acids and an acetylene click handle, wherein the amino acids are D-amino acids, artificial amino acids, or combinations thereof, and wherein the epitope of the IDO1 comprises an azide click handle, wherein the epitope comprises the amino acid sequence GFWEDPKEFAGGSAGQSSVFQ (SEQ ID NO:1), LPPILVYADCVLANWKKKDPNK (SEQ ID NO:2), or NKPLTYENMDVLFSFR (SEQ ID NO:3);
- (b) allowing a member of the library to covalently bind to the azide click handle of the epitope;
- and
- (c) identifying the amino acid sequence of the library member that covalently binds to the azide click handle of the epitope, wherein the identified amino acid sequence is selected for forming a binding agent having affinity for the epitope of IDO1.
Dependencies are inferred from the claim text.