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1. (WO2017148879) OBINUTUZUMAB AND RITUXIMAB VARIANTS HAVING REDUCED ADCP
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WHAT IS CLAIMED IS:

An antibody comprising a variant heavy chain region comprising at least one amino acid substitution relative to the parent non-substituted heavy chain region, wherein the heavy chain region of the parent non- substituted antibody comprises the amino acid residue Asn297 and/or Pro329, and wherein said substitution is Asn297Asp and/or Pro329Gly, wherein the residues are numbered according to the EU index as in Kabat, wherein ADCP function induced by the antibody comprising the variant heavy chain region is reduced compared to ADCP function induced by the parent non-substituted antibody, wherein the antibody comprising the variant heavy chain retains residual ADCP function.

The antibody according to claim 1, wherein induction of effector function is reduced compared to effector function induced by an antibody comprising the parent non- substituted heavy chain region.

The antibody according to any one of claims 1 or 2, wherein the antibody is an IgGl antibody.

The antibody according to any one of claims 1 to 3, wherein the parent non-substituted antibody is obinutuzumab or rituximab.

The antibody according to any one of claims 1 to 4, wherein FcyRIII binding by the antibody comprising the variant heavy chain region is abolished compared to binding to FcyRIII by the parent non-substituted antibody.

The antibody according to any one of claims 1 to 5, wherein ADCC function induced by the antibody comprising the variant heavy chain region is abolished or strongly reduced compared to ADCC function induced by the parent non-substituted antibody.

The antibody according to any one of claims 1 to 6, wherein FcyRI binding by the antibody comprising the variant heavy chain region is reduced compared to binding to FcyRI by the parent non-substituted antibody.

The antibody according to any one of claims 1 to 7, wherein the variant heavy chain
region comprises a further amino acid substitution relative to the parent non-substituted heavy chain region, wherein the heavy chain region of the parent non-substituted antibody comprises the amino acid residue Pro 151, and wherein said further substitution is at said amino acid residue Prol51, wherein direct cell death induced by the antibody comprising the variant heavy chain region is altered compared to direct cell death induced by the antibody comprising proline at position 151.

9. The antibody according to claim 8, wherein direct cell death induced by the antibody comprising the variant heavy chain region is increased compared to direct cell death induced by the antibody comprising proline at position 151.

10. The antibody according to any one of claim 8 or 9, wherein Prol51 is substituted with phenylalanine.

11. The antibody according to any one of claims 1 to 10, wherein the antibody specifically binds to CD20.

12. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 11 and a pharmaceutically acceptable carrier.

13. An antibody according to any one of claims 1 to 11 for use as a medicament.

14. An antibody according to any one of claims 1 to 11 for use in treating a disease selected from the group consisting of proliferative disorder and autoimmune disease.

15. An antibody for use according to claim 14, characterized in that said proliferative disorder is a CD20 expressing cancer.

16. A method for treating a disease selected from the group consisting of proliferative disorder and autoimmune disease comprising administering to an individual an effective amount of the antibody according to any one of claims 1 to 11.

17. The method according to claim 16, characterized in that said proliferative disorder is a CD20 expressing cancer.

18. Use of the antibody according to any one of claims 1 to 11 for the manufacture of a medicament.

19. The use of claim 18, wherein the medicament is for treatment of a disease selected from the group consisting of proliferative disorder and autoimmune disease.