Monoclonal antibodies with enhanced ADCC function

• US 7,931,895 B2
• Filed: 01/24/2005
• Issued: 04/26/2011
• Est. Priority Date: 04/12/2000
• Status: Expired due to Fees

• Current Assignee: Laboratoire francais du Fractionnement et des Biotechnologies
• Original Assignee: Lfb Biomedicaments (Agence des Participations de l’Etat)
• Inventors: De Romeuf, Christophe, Beliard, Roland, Nony, Emmanuel, Bihoreau, Nicolas, Glacet, Arnaud, Bourel, Dominique
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US11/039,877
• Publication Number:
  US 20050249722A1
• Time in Patent Office: 2,283 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C07K 16/34 against blood group antigens
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

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 isoimmunisation in Rh negative persons, in particular for haemolytic disease in a new-born baby of for uses such as idiopathic thrombocytopenic pupura 9ITP).

Claims

1. A monoclonal antibody composition comprising purified monoclonal antibodies having on the Fcγ

glycosylation sites (Asn 297, EU numbering) bi-antennary glycan structures

wherein said glycan structures of the purified monoclonal antibodies have a fucose content less than 65%, and

wherein said glycan structures of the purified monoclonal antibodies have a content greater than 60% for the G0+G1+G0F+G1F forms

2. The composition of claim 1, wherein the fucose content is less than 30%.

3. The composition of claim 1, wherein the fucose content is between 20% and 45%.

4. The composition of claim 1, wherein the fucose content is between 25% and 40%.

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.

21. The composition of claim 1, wherein said glycan structures of the purified monoclonal antibodies have a sialic acid content of less than 25%.

11. A monoclonal antibody composition comprising purified monoclonal antibodies having on the Fcγ

glycosylation sites (Asn 297, EU numbering) bi-antennary glycan structures,

wherein said glycan structures of the purified monoclonal antibodies have a content less than 50% for the G0F+G1F forms, and

wherein said glycan structures of the purified monoclonal antibodies have a content greater than 60% for the G0+G1+G0F+G1F forms.

12. The composition of claim 11, wherein said glycan structures of the purified monoclonal antibodies have a content less than 30% for the G0F+G1F forms.

13. The composition of claim 11, wherein said glycan structures of the purified monoclonal antibodies have a content greater than 80% for the G0+G1+G0F+G1F forms.

14. 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.

15. The composition of claim 14, 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.

16. The composition of claim 15, 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.

17. The composition of claim 16, 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.

18. The composition of claim 11, wherein said monoclonal antibodies are IgG1 antibodies.

19. The composition of claim 11, wherein said monoclonal antibodies are IgG3 antibodies.

20. The composition of claim 11, wherein said monoclonal antibodies are anti Rh(D) antibodies.

22. The composition of claim 11, wherein said glycan structures of the purified monoclonal antibodies have a sialic acid content of less than 25%.