Amyloid-beta binding proteins
View Patent ↗The present invention relates to amyloid-beta (Aβ) binding proteins. Antibodies of the invention have high affinity to Aβ(20-42) globulomer or any Aβ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.
1. An isolated antibody or antigen-binding portion thereof comprising:
a first amino acid sequence which is at least 90% identical to SEQ ID NO:2 or SEQ ID NO:3; and a second amino acid sequence which is at least 90% identical to SEQ ID NO:1,
wherein the first amino acid sequence comprises at least three complementarity determining regions consisting of amino acids 31-35, 50-65, and 98-101 respectively of SEQ ID NO:2 or SEQ ID NO:3;
wherein the second amino acid sequence comprises at least three complementarity determining regions consisting of amino acids 24-39, 55-61, and 94-102 respectively of SEQ ID NO:1; and
wherein the antibody or antigen-binding portion thereof has a binding affinity to an Aβ(20-42) globulomer that is greater than the binding affinity of the antibody or antigen-binding portion thereof to an Aβ(1-42) globulomer.
2. The isolated antibody or antigen-binding portion thereof according to claim 1 , wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.
3. The isolated antibody or antigen-binding portion thereof according to claim 1 , wherein the second amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16.
4. An isolated antibody or antigen-binding portion thereof according to any one of claims 1 to 3 comprising:
a first amino acid sequence which is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11; and a second amino acid sequence which is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16.
5. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein said antibody or antigen-binding portion thereof is selected from the group consisting of: a disulfide linked Fv, a monoclonal antibody, a scFv, a chimeric antibody, a CDR-grafted antibody, a diabody, a humanized antibody, a multispecific antibody, a Fab, a Fab′, a bispecific antibody, a F(ab′) 2 , and a Fv.
6. The isolated antibody or antigen-binding portion thereof of claim 1 further comprising an immunoglobulin light chain constant region having an amino acid sequence selected from the group consisting of SEQ ID NO:27 and SEQ ID NO:28.
7. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein said antibody or antigen-binding portion thereof further comprises an agent selected from the group consisting of: an immunoadhesion molecule, an imaging agent, and a therapeutic agent.
8. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein said antibody or antigen-binding portion thereof possesses a human glycosylation pattern.
9. An isolated antibody or antigen-binding portion thereof produced according to a method comprising culturing a host cell comprising a vector comprising an isolated nucleic acid encoding the isolated antibody or antigen-binding portion thereof of claim 1 .
10. A pharmaceutical composition comprising the isolated antibody or antigen-binding portion thereof of claim 1 , and a pharmaceutically acceptable carrier.
11. The pharmaceutical composition of claim 10 further comprising at least one additional therapeutic agent.