CHIMERIC ANTIBODIES
The present invention provides a chimeric antibody or an antigen-binding portion thereof. The antigen-binding portion comprises at least two complementarity determining regions (CDR) and at least three framework regions, wherein at least one CDR is a New World primate CDR
1 . A method of producing a chimeric antibody or an antigen-binding portion thereof, the method comprising deleting a CDR from a human antibody variable region comprising at least two CDRs and at least three framework regions and replacing it with a New World primate CDR predicted to be of low immunogenicity to produce a chimeric variable region.
2 . The method according to claim 1 wherein the method further comprises the step of recovering the chimeric variable region.
3 . The method according to claim 1 wherein the New World primate CDR is CDR2.
4 . The method according to claim 1 further comprising the step of modifying the sequence of the chimeric variable region to increase binding, provided that the New World primate CDR sequence is not modified.
5 . The method according to claim 1 further comprising the step of modifying the sequence of the chimeric variable region to decrease immunogenicity in humans, provided that the at least one New World primate CDR sequence is not modified.
6 . The method according to claim 1 wherein the New World primate is selected from the group consisting of marmosets, tamarins, squirrel monkey, titi monkey, spider monkey, woolly monkey, capuchin, uakaris, sakis, night or owl monkey and the howler monkey.
7 . The method according to claim 6 wherein the New World primate is a marmoset.
8 . The method according to claim 1 wherein the antibody binds to an antigen that is peptide, protein, carbohydrate, glycoprotein, lipid or glycolipid in nature, selected from a tumour-associated antigen including carcinoembryonic antigen, EpCAM, Lewis-Y, Lewis-Y/b, PMSA, CD20, CD30, CD33, CD38, CD52, CD154, EGF-R, Her-2, TRAIL and VEGF receptors, an antigen involved in an immune or inflammatory disease or disorder including CD3, CD4, CD25, CD40, CD49d, MHC class I, MHC class II, GM-CSF, interferon-γ, IL-1, IL-12, IL-13, IL-23, TNF-α, and IgE, an antigen expressed on a host cell including glycoprotein IIb/IIIa, P-glycoprotein, purinergic receptors and adhesion receptors including CD11a, CD11b, CD11c, CD18, CD56, CD58, CD62 or CD144, an antigen comprising a cytokine, chemokine, growth factor or other soluble physiological modulator or a receptor thereof including eotaxin, IL-6, IL-8, TGF-β, C3a, C5a, VEGF, NGF and their receptors, an antigen involved in central nervous system diseases or disorders including β-amyloid and prions, an antigen of non-human origin such as microbial, nanobial or viral antigens or toxins including respiratory syncitial virus protein F, anthrax toxin, rattle snake venom and digoxin.
9 . The method according to claim 8 , wherein the antibody binds to TNFα.
10 . A chimeric antibody or an antigen-binding portion thereof produced by the method according to claim 1 .