Human monoclonal antibodies to activin receptor-like kinase-1
View Patent ↗The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that bind to the extracellular domain (ECD) of activin receptor-like kinase-1 (ALK-1) and that function to abrogate the ALK-1/TGF-beta-1/Smad1 signaling pathway. The invention also relates to heavy and light chain immunoglobulins derived from human anti-ALK-1 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-ALK-1 antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention.
1. A monoclonal antibody, or an antigen-binding portion thereof, that binds activin receptor-like kinase-1 (ALK-1), comprising a first variable domain comprising SEQ ID NO: 6 and a second variable domain comprising SEQ ID NO: 8.
2. The monoclonal antibody of claim 1 , comprising the heavy chain amino acid sequence of SEQ ID NO: 2 and comprising the light chain amino acid sequence of SEQ ID NO: 4.
3. The monoclonal antibody of claim 1 , comprising a heavy chain that comprises SEQ ID NO: 6 and a light chain that comprises SEQ ID NO: 8.
4. The monoclonal antibody of claim 1 or 3 , the monoclonal antibody being selected from IgG1 or IgG2.
5. A monoclonal antibody, or an antigen-binding portion thereof, that binds ALK-1, wherein said antibody or antigen-binding portion comprises V H CDR1, CDR2 and CDR3 sequences in SEQ ID NO: 6 and V L CDR1,CDR2 and CDR3 sequences in SEQ ID NO: 8.
6. The antibody according to claim 1 that is an IgG, an IgM, an IgE, an IgA, or an IgD.
7. A pharmaceutical composition comprising the antibody or antigen-binding portion according to claim 1 and a physiologically acceptable carrier.
8. A monoclonal antibody, or an antigen-binding portion thereof, that binds ALK-1, the antibody comprising the V H amino acid sequence encoded by the nucleotide sequence of the plasmid insert found in the E. coli clone deposited under ATCC accession number PTA-6864 and the V L amino acid sequence encoded by the nucleotide sequence of the plasmid insert found in the E. coli clone deposited under ATCC accession number PTA-6865.
9. The antibody according to claim 3 that is an IgG, an IgM, an IgE, an IgA, or an IgD.
10. The antibody according to claim 5 that is an IgG, an IgM, an IgE, an IgA, or an IgD.
11. A pharmaceutical composition comprising the antibody according to claim 2 and a physiologically acceptable carrier.
12. A pharmaceutical composition comprising the antibody according to claim 3 and a physiologically acceptable carrier.
13. A pharmaceutical composition comprising the antibody or antigen-binding portion according to claim 5 and a physiologically acceptable carrier.
14. A pharmaceutical composition comprising the antibody or antigen-binding portion according to claim 8 and a physiologically acceptable carrier.
15. A hybridoma deposited under an ATTC accession number of PTA-6808.