Gremlin-1 antibody
This invention relates to crystals of the human Gremlin-1 protein, and the human Gremlin-1 protein in complex with an inhibitory antibody. The invention also relates to the structure of human Gremlin-1 (on its own, or in complex with the antibody) and uses of these structures in screening for agents which modulate Gremlin-1 activity. The invention further provides antibodies which bind an allosteric inhibitory site on Gremlin-1, together with pharmaceutical compositions and medical uses of such antibodies and agents identified by the screening methods.
1. A monoclonal anti-Gremlin-1 antibody comprising a HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 4/5/6/7/8/9 or SEQ ID NOs: 3/5/6/7/8/9.
2. The monoclonal anti-Gremlin-1 antibody according to claim 1 , wherein said anti-Gremlin-1 antibody is a chimeric antibody and comprises the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 4/5/6/7/8/9.
3. The monoclonal anti-Gremlin-1 antibody according to claim 1 , wherein said anti-Gremlin-1 antibody is a chimeric antibody and comprises the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 3/5/6/7/8/9.
4. The monoclonal anti-Gremlin-1 antibody according to claim 1 , wherein said anti-Gremlin-1 antibody is a humanized antibody and comprises the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 4/5/6/7/8/9.
5. The monoclonal anti-Gremlin-1 antibody according to claim 1 , wherein said anti-Gremlin-1 antibody is a humanized antibody and comprises the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 3/5/6/7/8/9.
6. The monoclonal anti-Gremlin-1 antibody according to claim 1 , wherein said anti-Gremlin-1 antibody is a human antibody and comprises the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 4/5/6/7/8/9.
7. The monoclonal anti-Gremlin-1 antibody according to claim 1 , wherein said anti-Gremlin-1 antibody is a human antibody and comprises the HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3 sequence combination of SEQ ID NOs: 3/5/6/7/8/9.
8. The monoclonal antibody according to claim 1 , wherein said antibody is a Fab, modified Fab, Fab′, modified Fab′, F(ab′) 2 , Fv, single domain antibody or an scFv.
9. The monoclonal antibody according to claim 1 , wherein said antibody comprises a light chain variable region selected from SEQ ID NO: 11 or 13 and a heavy chain variable region selected from SEQ ID NO: 10 or 12.
10. The monoclonal antibody according to claim 9 , wherein said antibody comprises SEQ ID NOs: 10 and 11.
11. The monoclonal antibody according to claim 9 , wherein said antibody comprises SEQ ID NOs: 12 and 13.
12. A pharmaceutical composition comprising a monoclonal antibody according to claim 1 and a pharmaceutically acceptable adjuvant and/or carrier.