CD20 binding molecules
The present invention relates to CD20 binding molecules and nucleic acid sequences encoding CD20 binding molecules. In particular, the present invention relates to CD20 binding molecules with a high binding affinity, and a low dissociation rate, with regard to human CD20. Preferably, the CD20 binding molecules of the present invention comprise light and/or heavy chain variable regions with fully human frameworks (e.g. human germline frameworks).
1. A composition comprising a CD20 binding molecule, wherein the CD20 binding molecule comprises a light chain variable region and a heavy chain variable region, wherein:
the light chain variable region comprises:
a CDRL1 amino acid sequence of SEQ ID NO:5;
a CDRL2 amino acid sequence of SEQ ID NO:13;
a CDRL3 amino acid sequence SEQ ID NO:19, and
the heavy chain variable region comprises:
a CDRH1 amino acid sequence of SEQ ID NO:25;
a CDRH2 amino acid sequence of SEQ ID NO:39; and
a CDRH3 amino acid sequence of SEQ ID NO:57.
2. A method of treating B cell lymphoma comprising administering to a subject a composition comprising a CD20 binding molecule, wherein the CD20 binding molecule comprises a light chain variable region and a heavy chain variable region, wherein:
the light chain variable region comprises:
a CDRL1 amino acid sequence of SEQ ID NO:5;
a CDRL2 amino acid sequence of SEQ ID NO:13; and
a CDRL3 amino acid sequence of SEQ ID NO:19, and
the heavy chain variable region comprises:
a CDRH1 amino acid sequence of SEQ ID NO:25;
a CDRH2 amino acid sequence of SEQ ID NO:39; and
a CDRH3 amino acid sequence of SEQ ID NO:57.
3. The method of claim 2 , wherein the CD20 binding molecule comprises the AME 33 Fab.
4. The method of claim 2 , wherein the CD20 binding molecule has a binding affinity (K d ) for human CD20 of 5.0×10 −10 M or less, and a dissociation rate (koff) for human CD20 of 5.0×10 −4 s −1 or less.
5. The method of claim 4 , wherein the CD20 binding molecule has a binding affinity (K d ) for human CD20 of 1.5×10 −10 M or less.
6. The method of claim 4 , wherein the CD20 binding molecule has a dissociation rate (k off ) for human CD20 of 2.5×10 −4 s −1 or less.
7. The method of claim 4 , wherein the CD20 binding molecule has an association rate (k on ) for human CD20 of 5.0×10 −5 M −1 s −1 or greater.
8. The method of claim 2 , wherein the B cell lymphoma is Non-Hodgkin's lymphoma.
9. The method of claim 8 , wherein the Non-Hodgkin's lymphoma is Waldenstrom's macroglobulinemia.
10. The composition of claim 1 , wherein the light chain variable region comprises an amino acid sequence of SEQ ID NO:59 and the heavy chain variable region comprises an amino acid sequence of SEQ ID NO:61.
11. A composition comprising a CD20 binding molecule, wherein the CD20 binding molecule comprises a light chain amino acid sequence of SEQ ID NO:67 and a heavy chain amino acid sequence of SEQ ID NO:69.