CD20 antibodies
CD20 antibodies with improved characteristics. Some embodiments describe antibodies comprising a mouse IgG2; a human IgG1, IgA1 or IgA2 constant region and a variable domain that can bind the epitope “EPANpSEK” (SEQ ID NO:31) on human CD20 expressed on Ramos cells and which antibody has an increased PCD functionality when compared to Rituximab with a constant region of the same isotype.
1. An isolated antibody that can bind to an extracellular part of human CD20 expressed on Ramos cells, the antibody comprising:
a variable domain with
a heavy chain variable region, and
a light chain variable region,
wherein the heavy chain variable region comprises a CDR1, CDR2 and CDR3 region with the sequence SYNLH (SEQ ID NO:26), ATYPGNGDTS YNOKFKG (SEQ ID NO: 27), and SNSYGSTYWYFDV (SEQ ID NO: 21), respectively, and
wherein the light chain variable region comprises a CDR1, CDR2 and CDR3 region with the sequence RARSSVSYMD (SEQ ID NO: 31), ATSNLAS (SEQ ID NO: 32), and QOQWTSNPPT (SEQ. ID NO: 33), respectively.
2. The antibody of claim 1 , wherein the heavy chain variable region comprises the sequence of SEQ ID NO: 1, with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than positions of the amino acids that constitute the CDR1, CDR2 and CDR3 regions.
3. The antibody of claim 1 , wherein the light chain variable region comprises the sequence of SEQ ID NO:2, with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than positions of the amino acids that constitute the CDR1, CDR2 and CDR3 regions.
4. An isolated antibody comprising:
a heavy chain that comprises the sequence of SEQ ID NO: 1 and the sequences of SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5, and
a light chain that comprises the sequence of SEQ ID NO:2 and the sequence of SEQ ID NO:6;
wherein the antibody has an increased Complement-Dependent Cytotoxicity (“CDC”) and/or increased antibody-dependent cellular cytotoxicity (“ADCC”) functionality when compared to Rituximab with a constant region of the same isotype.
5. The antibody of claim 1 , comprising a mouse IgG2; a human IgG1, human IgG2, human IgG3, human IgG4, human IgM, human IgE, human IgA heavy chain constant region or a combination thereof.
6. The antibody of claim 5 , comprising a human IgG1, human IgG2, human IgA1 or human IgA2 heavy chain constant region or a combination thereof.
7. The antibody of claim 1 , comprising a heavy chain and a light chain, wherein the heavy chain comprises the sequence of SEQ ID NO: 1 and the sequence of SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5 with 0-15 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than positions of the amino acids that constitute the CDR1, CDR2 and CDR3 regions.
8. The antibody of claim 1 , wherein the light chain comprises the sequence of SEQ ID NO:2 and the sequence of SEQ ID NO:6 with 0-15 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than positions of the amino acids that constitute the CDR1, CDR2 and CDR3 regions.
9. The antibody of claim 1 , wherein the antibody has an increased programmed cell death (“PCD”) functionality when compared to Rituximab with a constant region of the same isotype.
10. The antibody of claim 1 , wherein the heavy chain comprises the sequence of SEQ ID NO: 1 and the sequence of SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:5.
11. The antibody of claim 1 , wherein the light chain comprises the sequence of SEQ ID NO:2 and the sequence of SEQ ID NO:6.