Methods and compositions for inhibiting CD32B expressing cells

Patent metadata

Field	Value
Publication number	US-9394366-B2
Application number	US-201213689528-A
Country	US
Kind code	B2
Filing date	Nov 29, 2012
Priority date	May 30, 2007
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The present invention relates to immunoglobulins that bind FcγRIIb+ cells and coengage the antigen on the cell's surface and an FcγRIIb on the cell's surface, methods for their generation, and methods for using the immunoglobulins.

First claim

We claim:

1. A method of inhibiting BCR activation of at least one B cell comprising contacting the B cell with an anti-CD19 antibody comprising:
an Fc region that binds FcγRIIb on the cell surface with enhanced affinity as compared to a parent antibody comprising the amino acid sequence of SEQ ID NO:4;
a light chain comprising an amino acid sequence of SEQ ID NO: 7;
a heavy chain comprising an amino acid sequence of SEQ ID NO: 2; and
at least one amino acid substitution in the Fc region selected from: L235Y, L235R, G236D, S267D, S267E, and L328F as compared to SEQ ID NO: 4, wherein the numbering is according to the EU index, as in Kabat.

2. The method of claim 1 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235D/S267D, L235I/S267E, L235I/S267D, L235Y/S267D, G236D/S267E, G236D/S267D, S267E/L328F, S267D/L328F, H268D/S267E, H268D/S267D, H268E/S267E, H268E/S267D, G236D/S267E/L328F, and G236N/S267E/L328F.

3. The method of claim 1 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235Y/S267D, G236D/S267E, S267E/L328F, H268D/S267E, H268E/S267E, H268E/S267D, G236D/S267E/L328F, and G236D/S267E/L328F.

4. The method of claim 1 , wherein the amino acid substitution in the Fc region is S267E.

5. The method of claim 1 , wherein the amino acid substitution in the Fc region is L328F.

6. The method of claim 1 , wherein the antibody comprises Fc substitutions S267E/L328F.

7. The method of claim 1 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235Y/S267D, G236D/S267E, S267E/L328F, H268D/S267E, H268E/S267E, H268E/S267D, G236D/S267E/L328F, and G236D/S267E/L328F.

8. A method of treating an indication selected from systemic Sjogren's syndrome, multiple sclerosis, lupus erythematosus (SLE), discoid lupus, and lupus erythematosis, in a patient in need of such treatment, comprising administering to said patient an anti-CD19 antibody comprising:
an Fc region that binds FcγRIIb on the cell surface with enhanced affinity as compared to a parent antibody comprising the amino acid sequence of SEQ ID NO:4;
a light chain comprising an amino acid sequence of SEQ ID NO: 7;
a heavy chain comprising an amino acid sequence of SEQ ID NO: 2; and
at least one amino acid substitution in the Fc region selected from
L235Y, L235R, G236D, S267D, S267E, and L328F
as compared to SEQ ID NO: 4, wherein the numbering is according to the EU index, as in Kabat.

9. The method of claim 8 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235D/S267D, L235I/S267E, L235I/S267D, L235Y/S267D, G236D/S267E, G236D/S267D, S267E/L328F, S267D/L328F, H268D/S267E, H268D/S267D, H268E/S267E, H268E/S267D, G236D/S267E/L328F, and G236N/S267E/L328F.

10. The method of claim 8 , wherein the indication is selected from discoid lupus, lupus erythematosis, and systemic lupus erythematosus.

11. The method of claim 8 , wherein said antibody has reduced binding affinity for FcγRIIIa as compared to a parent antibody.

12. The method of claim 8 , wherein the antibody comprises Fc substitution S267E.

13. The method of claim 8 , wherein the antibody comprises Fc substitution L328F.

14. The method of claim 8 , wherein the antibody comprises Fc substitutions S267E and L328F.

15. A method of treating an indication selected from systemic Sjogren's syndrome, multiple sclerosis, lupus erythematosus (SLE), discoid lupus, and lupus erythematosis, in a patient in need of such treatment, comprising administering to said patient an anti-CD19 antibody comprising:
an Fc region that binds FcγRIIb on the cell surface with enhanced affinity as compared to a parent antibody comprising the amino acid sequence of SEQ ID NO:4;
a light chain comprising an amino acid sequence of SEQ ID NO: 7; and
a heavy chain comprising an amino acid sequence of SEQ ID NO: 2 and amino acid substitution(s) in the Fc region selected from
L235Y, L235R, G236D, S267D, S267E, and L328F
as compared to SEQ ID NO: 4, wherein the numbering is according to the EU index, as in Kabat;

wherein the antibody inhibits said at least one B cell to treat the indication.

16. The method of claim 15 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235D/S267D, L235I/S267E, L235I/S267D, L235Y/S267D, G236D/S267E, G236D/S267D, S267E/L328F, S267D/L328F, H268D/S267E, H268D/S267D, H268E/S267E, H268E/S267D, G236D/S267E/L328F, and G236N/S267E/L328F.

17. The method of claim 15 , wherein the indication is selected from discoid lupus, lupus erythematosis, and systemic lupus erythematosus.

18. The method of claim 15 , wherein said antibody has reduced binding affinity for FcγRIIIa as compared to a parent antibody.

19. The method of claim 15 , wherein the antibody comprises Fc substitution S267E.

20. The method of claim 15 , wherein the antibody comprises Fc substitution L328F.

21. The method of claim 15 , wherein the antibody comprises Fc substitutions S267E and L328F.

22. The method of claim 15 , wherein the indication is selected from discoid lupus, lupus erythematosis, and systemic lupus erythematosus.

Assignees

• Chu Seung Yup
• Desjarlais John R
• Karki Sher Bahadur
• Lazar Gregory Alan
• Moore Gregory L
• Vostiar Igor
• Xencor Inc

Inventors

• Chu Seung Yup
• Desjarlais John R
• Karki Sher Bahadur
• Lazar Gregory Alan
• Moore Gregory L
• Vostiar Igor

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title