Antibodies for molecular imaging of vulnerable plaques in atherosclerosis
Antibodies for molecular imaging of vulnerable plaques in atherosclerosis Antibody specifically binding to atherosclerosis lesions for in vivo imaging and methods for in vivo imaging of atherosclerosis lesions in a patient.
1. Antibody specifically binding to atherosclerosis lesions wherein said antibody or antibody fragment comprises at least a VH CDR1 comprising the amino acid sequence of SEQ ID No.1, a VH CDR2 comprising the amino acid sequence of SEQ ID No.2, a VL CDR1 comprising the amino acid sequence of SEQ ID No.3 and a VL CDR2 comprising the amino acid sequence of SEQ ID No.4; and comprising at least:
a VH CDR3 comprising the amino acid sequence of SEQ ID No.5 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.6, or
a VH CDR3 comprising the amino acid sequence of SEQ ID No.10 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.11, or
a VH CDR3 comprising the amino acid sequence of SEQ ID No.15 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.16, or
a VH CDR3 comprising the amino acid sequence of SEQ ID No.20 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.21.
2. The antibody according to claim 1 comprising at least:
a VH domain comprising the amino acid sequence of SEQ ID No.7 and a VL domain comprising the amino acid sequence of SEQ ID No.8, or
a VH domain comprising the amino acid sequence of SEQ ID No.12 and a VL domain comprising the amino acid sequence of SEQ ID No.13, or
a VH domain comprising the amino acid sequence of SEQ ID No.17 and a VL domain comprising the amino acid sequence of SEQ ID No.18, or
a VH domain comprising the amino acid sequence of SEQ ID No.22 and a VL domain comprising the amino acid sequence of SEQ ID No.23.
3. The antibody according to claim 1 or 2 wherein the antibody is a recombinant human IgG.
4. The antibody according to claim 1 or 2 wherein the antibody is a recombinant human Fab′2, recombinant human scFv-Fab′2 or recombinant human scFv-Fc.
5. The antibody according to claim 1 or 2 wherein the antibody is a recombinant human scFv antibody.
6. The antibody according to claim 1 or 2 wherein the antibody is a recombinant human scFv antibody selected in the group consisting of:
the scFv antibody of SEQ ID No.9,
the scFV antibody of SEQ ID No.14,
the scFV antibody of SEQ ID No.19,
the scFv antibody of SEQ ID No.24.
7. A polynucleotide encoding an antibody according to claim 1 .
8. A recombinant host cell comprising a polynucleotide encoding an antibody according to claim 1 .
9. The antibody according to claim 1 , 2 or 6 wherein said antibody is labeled for in vivo imaging.
10. The antibody according to claim 9 wherein the antibody is labeled with a radiotracer for Nuclear Imaging or wherein the antibody is labeled with a magnetic contrast agent for Magnetic Resonance Imaging.
11. A method for in vivo imaging of atherosclerosis lesions in a patient comprising visualization of the atherosclerosis lesions by detection of a labeled antibody previously administered to the patient wherein the antibody is an antibody according to claim 9 .
12. The method according to claim 11 wherein the antibody is labeled with a radiotracer and visualization of the atherosclerosis lesions is performed by Nuclear Imaging.
13. The method according to claim 11 wherein the antibody is labeled with a contrast agent and visualization of the atherosclerosis lesions is performed by Magnetic Resonance Imaging.
14. A method for in vivo imaging of atherosclerosis lesions in a patient comprising the following steps:
a) Intravenous injection of an antibody according to claim 9 labeled for in vivo imaging into the patient,
b) Visualization of the atherosclerosis lesions by detection of the labeled antibody of step a) in the patient.
15. An antibody specifically binding to atherosclerosis lesions wherein said antibody or antibody fragment comprises at least a VH CDR1 comprising the amino acid sequence of SEQ ID No.1, a VH CDR2 comprising the amino acid sequence of SEQ ID No.2, a VL CDR1 comprising the amino acid sequence of SEQ ID No.3 and a VL CDR2 comprising the amino acid sequence of SEQ ID No.4; and comprising at least:
a VH CDR3 comprising the amino acid sequence of SEQ ID No.25 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.26, or
a VH CDR3 comprising the amino acid sequence of SEQ ID No.30 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.31, or
a VH CDR3 comprising the amino acid sequence of SEQ ID No.35 and a VL CDR3 comprising the amino acid sequence of SEQ ID No.36.
16. The antibody according to claim 15 comprising at least:
a VH domain comprising the amino acid sequence of SEQ ID No.27 and a VL domain comprising the amino acid sequence of SEQ ID No.28, or
a VH domain comprising the amino acid sequence of SEQ ID No.32 and a VL domain comprising the amino acid sequence of SEQ ID No.33, or
a VH domain comprising the amino acid sequence of SEQ ID No.37 and a VL domain comprising the amino acid sequence of SEQ ID No.38.
17. The antibody according to claim 15 or 16 wherein the antibody is a recombinant human IgG.
18. The antibody according to claim 15 or 16 wherein the antibody is a recombinant human Fab′2, recombinant human scFv-Fab′2 or recombinant human scFv-Fc.
19. The antibody according to claim 15 or 16 wherein the antibody is a recombinant human scFv antibody.
20. The antibody according to claim 15 or 16 wherein the antibody is a recombinant human scFv antibody selected in the group consisting of:
the scFv antibody of SEQ ID No.29,
the scFv antibody of SEQ ID No.34, and
the scFv antibody of SEQ ID No.39.
21. A polynucleotide encoding an antibody according to claim 15 .
22. A recombinant host cell comprising a polynucleotide encoding an antibody according to claim 15 .
23. The antibody according to claim 15 , 16 or 20 wherein said antibody is labeled for in vivo imaging.
24. The antibody according to claim 23 wherein the antibody is labeled with a radiotracer for Nuclear Imaging or wherein the antibody is labeled with a magnetic contrast agent for Magnetic Resonance Imaging.
25. A method for in vivo imaging of atherosclerosis lesions in a patient comprising visualization of the atherosclerosis lesions by detection of a labeled antibody previously administered to the patient wherein the antibody is an antibody according to claim 23 .
26. The method according to claim 25 wherein the antibody is labeled with a radiotracer and visualization of the atherosclerosis lesions is performed by Nuclear Imaging.
27. The method according to claim 25 wherein the antibody is labeled with a contrast agent and visualization of the atherosclerosis lesions is performed by Magnetic Resonance Imaging.
28. A method for in vivo imaging of atherosclerosis lesions in a patient comprising the following steps:
e) Intravenous injection of an antibody according to claim 23 labeled for in vivo imaging into the patient,
f) Visualization of the atherosclerosis lesions by detection of the labeled antibody of step a) in the patient.