Monoclonal antibodies with enhanced ADCC function

• US 20050249722A1
• Filed: 01/24/2005
• Published: 11/10/2005
• Est. Priority Date: 04/12/2000
• Status: Active Grant

• Current Assignee: Laboratoire francais du Fractionnement et des Biotechnologies
• Original Assignee: Laboratoire francais du Fractionnement et des Biotechnologies
• Inventors: Beliard, Roland, Glacet, Arnaud, Bourel, Dominique
• Granted Patent: US 7,931,895 B2
• Time in Patent Office: Days
• US Class Current: 424/131.100
• 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 having on its Fcγ

glycosylation site (Asn

     297) short chain bi-antennary glycan structures, with a low degree of sialylation and nonintercalated mannose or nonintercalated GlcNAc at a terminal point of attachment, wherein said glycan structures are selected from the group consisting of

and wherein said antibody has a fucose content less than 65%.

2. The monoclonal antibody of claim 1 having the fucose content less than 30%.

3. The monoclonal antibody of claim 1 having the fucose content between 20% and 45%.

4. The monoclonal antibody of claim 1 having the fucose content between 25% and 40%.

5. The monoclonal antibody of claim 1 directed against an antigen, wherein said antibody activates effector cells expressing Fcγ

type III receptors, causing a lysis of target cells presenting said antigen greater than 60% of a lysis caused by polyclonal antibodies directed against said antigen.

6. The monoclonal antibody of claim 5, wherein said antigen is rhesus D.

7. The monoclonal antibody of claim 1 directed against an antigen, wherein said antibody activates effector cells expressing Fcγ

type III receptors, causing a lysis of target cells presenting said antigen greater than 90% of a lysis caused by polyclonal antibodies directed against said antigen.

8. The monoclonal antibody of claim 7, wherein said antigen is rhesus D.

9. The monoclonal antibody of claim 1, wherein said antibody is IgG1.

10. The monoclonal antibody of claim 1, wherein said antibody is IgG3.

11. A pharmaceutical composition comprising one or more of antibodies of claim 1.

12. A pharmaceutical composition comprising one or more of antibodies of claim 1, wherein more than 60% of the antibodies have the glycan structures selected from the group consisting of G0, G1, G0F and G1F, and less than 50% of the antibodies have the glycan structures selected from the group consisting of G0F and G1F.

13. A pharmaceutical composition comprising one or more of antibodies of claim 1, wherein more than 80% of the antibodies have the glycan structures selected from the group consisting of G0, G1, G0F and G1F, and less than 30% of the antibodies have the glycan structures selected from the group consisting of G0F and G1F.

14. A method of treating cancer comprising administering the pharmaceutical composition of claim 12 to a patient in need of such treatment.

15. A method of treating infections caused by viral or bacterial pathogenic agents comprising administering the pharmaceutical composition of claim 12 to a patient in need of such treatment.

16. A method of prevention of Rhesus alloimmunization in Rh-negative individuals comprising administering the pharmaceutical composition of claim 12 to a patient in need of such treatment.

17. A method of protection of Rhesus-negative women immediately after a birth of a Rhesus-positive child, and of prevention of hemolytic disease of a newborn (HDN) at a time of subsequent pregnancies, comprising administering the pharmaceutical composition of claim 12 to a patient in need of such treatment.

18. A method of treatment of Idiopathic Thrombocytopenic Purpura (ITP) comprising administering the pharmaceutical composition of claim 12 to a patient in need of such treatment.