Back to results
US 2003/0190676 A1Published application
Antibody targeting compounds
AssigneeThe Scripps Research Institute
InventorsCarlos F. Barbas, Christoph Rader, Subhash C. Sinha, Richard A. Lerner
Life of this patent
Estimating the term…
Abstract
The present invention provides antibody targeting compounds in which the specificity of the antibody has been reprogrammed by covalently or noncovalently linking a targeting agent to the combining site of an antibody. By this approach, the covalently modified antibody takes on the binding specificity of the targeting agent. The compound may have biological activity provided by the targeting agent or by a separate biological agent. Various uses of the invention compounds are provided.
Claims66
An integrin targeting compound comprising, an RGD peptidomimetic-antibody complex wherein:
- a) said RGD peptidomimetic binds to one or both of αvβ3 and αvβ5;
- b) said antibody does not bind to αvβ3 or αvβ5;
- c) said complex results from an association between the RGD peptidomimetic and the combining site of the antibody;
- and
- d) said integrin targeting compound competes for binding between one or both of αvβ3 and αvβ5 and a protein selected from the group consisting of vitronectin, and fibrinogen.
2 more elements
An agent-linker-antigen compound for noncovalently linking to the combining site of an antibody, wherein:
- a) said agent is an RGD peptidomimetic that binds to one or both of αvβ3 and αvβ5;
- b) said antigen comprises at least one antigenic determinant recognized by the antibody combining site;
- c) said said linker is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof.
- d) said agent-linker-antigen compound competes for binding between one or both of αvβ3 and αvβ5 and a protein selected from the group consisting of vitronectin and fibrinogen.
1 more element
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is an RGD peptidomimetic that binds to one or both of αvβ3 and αvβ5;
- b) said linker is of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof,
- Y if present is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring;
- and
- Z is a ketone, diketone, beta lactam, active ester, haloketone, lactone, anhydride, epoxide, aldehyde, maleimide disulfide, or aryl halide;
- wherein Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody, said targeting agents or biological agents linked to X or Y if present or both X and Y if Y is present;
- and
- c) said agent-linker compound competes for binding between one or both of αvβ3 and αvβ5 and a protein selected from the group consisting of vitronectin, and fibrinogen.
8 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is an RGD peptidomimetic that binds to one or both of αvβ3 and αvβ5;
- b) said linker of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof, and comprising a repeating ether unit of between 0-100 units;
- Y is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring located within 1-20 atoms of Z;
- and
- Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody;
- and
- c) said agent-linker compound competes for binding between one or both of αvβ3 and αvβ5 and a protein selected from the group consisting of vitronectin and fibrinogen.
7 more elements
The agent-linker of claim 126 wherein X is a hetercarbyl of the formula
- 13
- wherein
- R2 to R4 is C, H, N, O, P, S, Si, halogen (F, Cl, Br, I) or a salt thereof
- n is 1-100 and
- m is 1-100
2 more elements
A CCR5 targeting compound comprising, a CCR5 chemokine peptidomimetic-antibody complex wherein:
- a) said CCR5 chemokine peptidomimetic binds to CCR5;
- b) said antibody does not bind to CCR5
- c) said complex results from an association between the CCR5 chemokine peptidomimetic and the combining site of the antibody;
- and
- d) said CCR5 targeting compound competes for binding between CCR5 and a β-chemokine.
2 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is a CCR5 peptidomimetic that binds to CCR5;
- b) said linker is of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof,
- Y if present is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring;
- and
- Z is a ketone, diketone, beta lactam, active ester, haloketone, lactone, anhydride, epoxide, aldehyde, maleimide disulfide, or aryl halide;
- wherein Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody, said targeting agents or biological agents linked to X or Y if present or both X and Y if Y is present;
- and
- c) said agent-linker compound competes for binding between CCR5 and a β-chemokine.
8 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is a CCR5 peptidomimetic that binds to CCR5;
- b) said linker of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof, and comprising a repeating ether unit of between 0-100 units;
- Y is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring located within 1-20 atoms of Z;
- and
- Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody;
- and
- c) said agent-linker compound competes for binding between CCR5 and β-chemokine.
7 more elements
A LHRH targeting compound comprising, an LHRH peptide-antibody complex wherein:
- a) said LHRH peptide binds to the LHRH receptor;
- b) said antibody does not bind to the LHRH receptor,
- c) said complex results from an association between the LHRH peptide and the combining site of the antibody;
- and
- d) said LHRH targeting compound competes for binding between LHRH and the LHRH receptor.
2 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is an LRHR peptide that binds to the LHRH receptor;
- b) said linker is of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof,
- Y if present is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring;
- and
- Z is a ketone, diketone, beta lactam, active ester, haloketone, lactone, anhydride, epoxide, aldehyde, maleimide disulfide, or aryl halide;
- wherein Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody, said targeting agents or biological agents linked to X or Y if present or both X and Y if Y is present;
- and
- c) said agent-linker compound competes for binding between LHRH and the LHRH receptor.
8 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is an LHRH peptide that binds to the LHRH receptor;
- b) said linker of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof, and comprising a repeating ether unit of between 0-100 units;
- Y is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring located within 1-20 atoms of Z;
- and
- Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody;
- and
- c) said agent-linker compound competes for binding between LHRH and the LHRH receptor.
7 more elements
An HIV-1 membrane fusion inhibiting compound-antibody complex wherein:
- a) said HIV-1 membrane fusion inhibiting compound inhibits fusion of HIV-1 to a target cell;
- b) said antibody does not inhibit fusion of HIV-1 to a target cell;
- and
- c) said complex results from an association between the HIV-1 membrane fusion inhibiting compound and the combining site of the antibody.
1 more element
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is an HIV-1 membrane fusion inhibiting compound;
- b) said linker is of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof,
- Y if present is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring;
- and
- Z is a ketone, diketone, beta lactam, active ester, haloketone, lactone, anhydride, epoxide, aldehyde, maleimide disulfide, or aryl halide;
- wherein Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody, said targeting agents or biological agents linked to X or Y if present or both X and Y if Y is present;
- and
- c) said agent-linker compound inhibits HIV-1 fusion to a cell membrane.
8 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is HIV-1 membrane fusion inhibiting compound;
- b) said linker of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof, and comprising a repeating ether unit of between 0-100 units;
- Y is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring located within 1-20 atoms of Z;
- and
- Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody;
- and
- c) said agent-linker compound inhibits HIV-1 fusion to a cell membrane.
7 more elements
A thrombopoietin (TPO) receptor targeting compound comprising, a TPO peptide or peptidomimetic-antibody complex wherein:
- a) said peptide or peptidomimetic binds to the TPO receptor;
- b) said antibody does not bind to the TPO receptor;
- c) said complex results from an association between the peptide or peptidomimetic and the combining site of the antibody;
- and
- d) said TPO receptor targeting compound competes for binding between TPO and the TPO receptor.
2 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is a thrombopoietin (TPO) receptor peptide or peptidomimetic that binds to the TPO receptor;
- b) said linker is of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, ora salt thereof,
- Y if present is a single or fused 5 or 6 membered homo- or heterocarbocylic saturated or unsaturated ring;
- and
- Z is a ketone, diketone, beta lactam, active ester, haloketone, lactone, anhydride, epoxide, aldehyde, maleimide disulfide, or aryl halide;
- wherein Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody, said targeting agents or biological agents linked to X or Y if present or both X and Y if Y is present;
- and
- c) said agent-linker compound competes for binding between TPO and the TPO receptor.
8 more elements
An agent-linker compound for covalently linking to a combining site of an antibody, wherein:
- a) said agent is a thrombopoietin (TPO) receptor peptide or peptidomimetic that binds to the TPO receptor;
- b) said linker of the formula
- X—Y—Z
- wherein
- X is a linear or branched connecting chain of atoms comprising any of C, H, N, O, P, S, Si, F, Cl, Br, and I, or a salt thereof, and comprising a repeating ether unit of between 0-100 units;
- Y is a single or fused 5 or 6 membered home or heterocarbocylic saturated or unsaturated ring located within 1-20 atoms of Z;
- and
- Z is a reactive group for covalently linking the agent to a side chain of a reactive amino acid in the combining site of the antibody;
- and
- c) said agent-linker compound competes for binding between TPO and the TPO receptor.
7 more elements
Dependencies are inferred from the claim text.