Anti-VCAM-1 nanobodies
The present invention relates to nanobodies specifically directed against VCAM-1 and to their use in medical imaging and in diagnostic, prognostic and treatment methods.
1. A nanobody directed against VCAM-1 comprising:
a) the amino acid sequences (i) YTNSIMYMA (SEQ ID NO: 1) as CDR1, (ii) AIRFPDDS (SEQ ID NO: 2) as CDR2 and (iii) RSSPYSFAWNDPSNYNY (SEQ ID NO: 3) as CDR3; or
b) the amino acid sequences (i) FTYSSYYMS (SEQ ID NO: 4) as CDR1, (ii) GINVDGSN (SEQ ID NO: 5) as CDR2 and (iii) GSGRDSYDCYSGSWCP (SEQ ID NO: 6) as CDR3; or
c) the amino acid sequences (i) FTFSNYYMT (SEQ ID NO: 7) as CDR1, (ii) RINSDGS (SEQ ID NO: 8) as CDR2 and (iii) GKSSV (SEQ ID NO: 9) as CDR3; or
d) the amino acid sequences (i) FTFSSYYMS (SEQ ID NO: 10) as CDR1, (ii) GINVDGSN (SEQ ID NO: 11) as CDR2 and (iii) GSGRDSYDCYSGSWCP (SEQ ID NO: 12) as CDR3.
2. The nanobody according to claim 1 , said nanobody comprising an amino acid sequence selected from the group consisting of the amino acid sequences SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16.
3. The nanobody according to claim 1 , said nanobody consisting of the amino acid sequence SEQ ID NO: 13.
4. The nanobody according to claim 1 , said nanobody being associated with a detectable marker.
5. The nanobody according to claim 4 , said detectable marker being a radionuclide.
6. An in vivo non-invasive medical imaging method comprising:
administering the nanobody according to claim 4 to a patient, and
detecting the nanobody in body areas of the patient.
7. A diagnostic or prognostic method of detecting an atheroma plaque in a patient comprising:
administering to the patient a nanobody according to claim 4 , and
detecting the nanobody in a region of the atheroma plaque in the patient.
8. A method of administering a nanobody directed against VCAM-1 to a patient comprising;
administering a therapeutically effective amount of the nanobody according to claim 1 to the patient.
9. An in vivo method of detecting VCAM-1 in a patient comprising:
contacting the patient with the nanobody as defined in claim 4 , and
detecting the nanobody bound to VCAM-1 in the patient.
10. A pharmaceutical composition comprising a nanobody as defined in claim 1 in association with a pharmaceutically acceptable carrier.
11. The method according to claim 8 , wherein the nanobody binds to and stabilizes an atheroma plaque.
12. The method according to claim 8 , wherein the nanobody is coupled to a stabilizer of an atheroma plaque.
13. The method according to claim 12 , wherein the stabilizer of an atheroma plaque is an anti-inflammatory molecule.
14. The method according to claim 13 , wherein the anti-inflammatory molecule is a non-steroidal anti-inflammatory agent.