antibodies binding to a C-terminal fragment of apoliopoprotein E
View Patent ↗A human antibody fragment, which antibody or fragment: (i) binds to a polypeptide having the amino acid sequence shown in SEQ ID NO: 1 of the C-terminal domain of Apolipoprotein E (ApoE-CTD) or the amino acid sequence of a part thereof; and (ii) binds to human plaques.
1. An isolated human, humanised or chimeric antibody or antibody fragment, which antibody or fragment:
(i) binds to a polypeptide having the amino acid sequence shown in SEQ ID NO: 1 of the C-terminal domain of Apolipoprotein E (ApoE-CTD) or the amino acid sequence of a part thereof;
(ii) binds to human plaques; and
(iii) comprises:
(a) a heavy chain CDR3 region comprising the sequence shown in SEQ ID NO: 26, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, or SEQ ID NO: 512;
(b) a heavy chain CDR2 region comprising the sequence shown in SEQ ID NO: 25;
(c) a heavy chain CDR1 region comprising the sequence shown in SEQ ID NO: 24;
(d) a light chain CDR3 region comprising the sequence shown in SEQ ID NO: 35;
(e) a light chain CDR2 region comprising the sequence shown in SEQ ID NO: 34; and
(f) a light chain CDR1 region comprising the sequence shown in SEQ ID NO: 33.
2. An antibody or antibody fragment according to claim 1 , wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 512.
3. An antibody or antibody fragment according to claim 1 , wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 20.
4. An antibody or antibody fragment according to claim 1 wherein said heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 23.
5. An antibody or antibody fragment according to claim 2 wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209 or SEQ ID NO: 210.
6. An antibody or antibody fragment according to claim 5 , wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 207, SEQ ID NO: 208 or SEQ ID NO: 209.
7. An antibody or antibody fragment according to claim 1 , wherein said polypeptide having the amino acid sequence of a part of SEQ ID NO: 1 comprises the sequence shown in SEQ ID NO: 5.
8. An antibody or antibody fragment according to claim 1 , wherein said ApoE-CTD polypeptide is a recombinant polypeptide.
9. An antibody or antibody fragment according to claim 8 wherein said recombinant polypeptide is biotinylated.
10. An antibody or antibody fragment according to claim 1 , which binds to said plaques in the presence of VLDL.
11. An antibody or antibody fragment according to claim 1 , wherein said VLDL is present in human plasma.
12. An antibody or antibody fragment according to claim 11 , which binds to the plaques in the presence of 25% plasma.
13. An antibody or antibody fragment according to claim 12 , which binds to the plagues in the presence of from 25% to 50% plasma.
14. An antibody or antibody fragment according to claim 13 , which binds to the plaques in the presence of 50% plasma.
15. An isolated antibody or antibody fragment which comprises:
(a) the heavy chain sequence shown in SEQ ID NO: 40 and the light chain sequence shown in SEQ ID NO: 518 and/or 519 or
(b) the heavy chain sequence shown in SEQ ID NO: 40 and the light chain sequence shown in SEQ ID NO: 520 and/or 521.
16. An isolated antibody or antibody fragment which comprises:
(a) the heavy chain CDR1 sequence shown in SEQ ID NO: 24, the heavy chain CDR2 sequence shown in SEQ ID NO: 25 and the heavy chain CDR3 sequence shown in any one of SEQ ID NOS: 207, 209 and 210; and
(b) the light chain ODR1, CDR2 and CDR3 sequences shown in SEQ ID NOS: 33, 34 and 35, SEQ ID NOS: 219, 247 and 269, SEQ ID NOS: 226, 252 and 275 or SEQ ID NOS: 218, 34 and 268.
17. An antibody or antibody fragment according to claim 16 wherein the heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 210 and the light chain comprises the sequences shown in SEQ ID NOS: 33, 34 and 35, the heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 209 and the light chain comprises the sequences shown in SEQ ID NOS: 219, 247 and 269 or SEQ ID NOS: 218, 34 and 268, or the heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 207 and the light chain comprises the sequence shown in SEQ ID NOS: 226, 252 and 275.
18. An antibody or antibody fragment according to claim 16 , wherein the heavy chain comprises the sequence shown in any one of SEQ ID NO: 317, 318 or 319.
19. An antibody or antibody fragment according to claim 16 , wherein the light chain comprises the sequence shown in SEQ ID NO: 43, 295, 294 or 304.
20. An antibody or antibody fragment according to claim 1 , wherein said antibody is an lgG.
21. An antibody or antibody fragment according to claim 1 , wherein said antibody fragment is a Fab fragment or scFv.
22. An antibody or antibody fragment according to claim 1 , which is a monoclonal antibody.
23. An antibody or antibody fragment according to claim 1 , which is a humanised antibody.
24. An antibody or antibody fragment according to claim 1 , which is chimeric.
25. A pharmaceutical composition comprising an antibody or antibody fragment according to claim 1 and a pharmaceutically acceptable carrier or diluent.
26. A kit for detecting ApoE-CTD, which kit comprises an antibody or antibody fragment according to claim 1 and means for detecting said an antibody or antibody fragment.
27. An antibody or antibody fragment according to claim 1 , which is a human antibody.