Anti-PLGF antibody
View Patent ↗The present invention provides novel monoclonal antibodies directed to PlGF and fragments and derivatives thereof, more particularly to humanized antibodies and fragments thereof for use in the treatment and/or prevention of pathological angiogenesis.
1. An isolated antibody capable of binding to human PlGF or an antigen-binding fragment of said antibody, wherein said antibody comprises a variable heavy chain sequence of which the sequence of the CDR1, CDR2, and CDR3 region corresponds to the sequence of SEQ ID NO: 17, 18, and 19, respectively, and comprises a variable light chain sequence of which the sequence of the CDR1, CDR2, and CDR3 region corresponds to the sequence of SEQ ID NO: 20, 21, and 22, respectively.
2. The antigen-binding fragment according to claim 1 , which is selected from the group consisting of a Fab, Fab′, and F(ab′)2.
3. The antibody according to claim 1 , comprising a variable heavy chain comprising the sequence of SEQ ID NO:2 or a sequence having at least 95% sequence identity therewith outside the CDR regions and comprising a variable light chain comprising the sequence of SEQ ID NO:4 or a sequence having at least 95% sequence identity therewith outside the CDR regions.
4. The antibody according to claim 1 , which is the antibody 16D3 as produced by the cell line deposited as LMBP 6399CB.
5. The antibody or antigen-binding fragment of said antibody according to claim 1 , which is a humanized antibody or antigen binding fragment thereof.
6. The antibody or antigen-binding fragment of said antibody of claim 1 , which comprises the amino acid sequence of SEQ ID NO:24.
7. The antibody or antigen-binding fragment of said antibody of claim 1 , which comprises the amino acid sequence of SEQ ID NO:26.
8. A cell line producing an antibody according to claim 1 .
9. The cell line according to claim 8 , which is the cell line deposited as LMBP 6399CB.
10. A pharmaceutical composition, comprising as an active ingredient an antibody or antigen-binding fragment of said antibody according to claim 1 in an admixture with a pharmaceutically acceptable carrier.
11. The pharmaceutical composition according to claim 10 , further comprising a therapeutically effective amount of another anti-angiogenic agent.
12. A method of treatment of undesired angiogenesis in a pathological condition in a mammal, comprising administering to a mammal in need of such treatment a therapeutically effective amount of an antibody or an antigen-binding fragment of said antibody according to claim 1 .
13. The method according to claim 12 , wherein the pathological condition is selected from the group consisting of cancer, inflammation, adhesion formation, diseases of the eye, pulmonary hypertension and vascular leakage.
14. The method of claim 13 , wherein said cancer is selected from the group consisting of colon cancer, breast cancer, pancreatic cancer, and melanomas.
15. A method of immunological detection of PlGF in human samples comprising contacting a human sample with the antibody or antigen-binding fragment of said antibody of claim 1 , and detecting the binding of said antibody or antigen-binding fragment of said antibody.
16. A method of screening for compounds with an additive effect to PlGF inhibition in the treatment of cancer, comprising administering to an animal tumor model an antibody or antigen-binding fragment of said antibody of claim 1 and a test compound, and identifying whether the compound has an additive effect to the effect observed upon administration of the antibody or antigen-binding fragment of said antibody.
17. The antigen-binding fragment according to claim 1 , which is an antigen-binding fragment of the antibody 16D3 as produced by the cell line deposited as LMBP 6399CB.