Monoclonal antibodies with enhanced ADCC function
The invention concerns a method for obtaining and selecting monoclonal antibodies by an ADDC-type test, said antibodies capable of activating type III Fcy receptors and having a particular glycan structure. The inventive anti-D antibodies can be used for preventing Rhesus isoimmunization in Rh negative persons, in particular for haemolytic disease in a new-born baby of for uses such as idiopathic thrombocytopenic purpura (ITP).
1. A monoclonal antibody composition comprising purified monoclonal antibodies having on the Fcγ glycosylation site (Asn 297, EU numbering) bi-antennary glycan structures,
wherein said glycan structures of the purified monoclonal antibodies have a fucose content less than 30%.
2. The composition of claim 1 , wherein the fucose content is between 20% and 30%.
3. The composition of claim 2 , wherein the fucose content is between 25% and 30%.
4. The composition of claim 1 , wherein said glycan structures of the purified monoclonal antibodies have a sialic acid content of less than 25%.
5. The composition of claim 1 , wherein the purified monoclonal antibodies are directed against an antigen, and activate effector cells expressing Fcγ type III receptors, causing a lysis of target cells presenting the antigen greater than 60% of a lysis caused by polyclonal antibodies directed against the antigen.
6. The composition of claim 5 , wherein the antigen is rhesus D.
7. The composition of claim 1 , wherein the purified monoclonal antibodies are directed against an antigen, and activate effector cells expressing Fcγ type III receptors, causing a lysis of target cells presenting the antigen greater than 90% of a lysis caused by polyclonal antibodies directed against the antigen.
8. The composition of claim 7 , wherein the antigen is rhesus D.
9. The composition of claim 1 , wherein the purified monoclonal antibodies are IgG1 antibodies.
10. The composition of claim 1 , wherein the purified monoclonal antibodies are IgG3 antibodies.
11. A monoclonal antibody composition comprising purified monoclonal antibodies having on the Fcγ glycosylation site (Asn 297, EU numbering) bi-antennary glycan structures,
wherein said glycan structures of the purified monoclonal antibodies have a content less than 30% for the G0F+G1F forms.
12. The composition of claim 11 , wherein said glycan structures of the purified monoclonal antibodies have a sialic acid content of less than 25%.
13. The composition of claim 11 wherein the monoclonal antibodies are directed against an antigen, and activate effector cells expressing Fcγ type III receptors, causing a lysis of target cells presenting the antigen greater than 60% of a lysis caused by polyclonal antibodies directed against the antigen.
14. The composition of claim 13 wherein the monoclonal antibodies cause a lysis of target cells presenting the antigen greater than 70% of a lysis caused by polyclonal antibodies directed against the antigen.
15. The composition of claim 14 wherein the monoclonal antibodies cause a lysis of target cells presenting the antigen greater than 80% of a lysis caused by polyclonal antibodies directed against the antigen.
16. The composition of claim 15 , wherein the monoclonal antibodies cause a lysis of target cells presenting the antigen greater than 90% of a lysis caused by polyclonal antibodies directed against the antigen.
17. The composition of claim 11 , wherein said monoclonal antibodies are IgG1 antibodies.
18. The composition of claim 11 , wherein said monoclonal antibodies are IgG3 antibodies.
19. The composition of claim 11 , wherein said monoclonal antibodies are anti Rh(D) antibodies.