Methods and compositions for inhibiting CD32B expressing cells

• US 9,079,960 B2
• Filed: 08/24/2012
• Issued: 07/14/2015
• Est. Priority Date: 05/30/2007
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Chu, Seung Yup, Desjarlais, John R., Karki, Sher Bahadur, Lazar, Gregory Alan, Moore, Gregory L., Vostiar, Igor
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US13/594,619
• Publication Number:
  US 20120321620A1
• Time in Patent Office: 1,054 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/283 against Fc-receptors, e.g. CD16, CD32, CD64 CD23 C07K16/2851
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/524 CH2 domain
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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.

Claims

1. An anti-CD19 immunoglobulin comprising:

a light chain; 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 L234W, L235I, L235Y, L235R, L235D, G236D, G236N, S267D, S267E, L328F, and L328Y as compared to SEQ ID NO;

4, wherein the numbering is according to the EU index, as in Kabat.

2. The immunoglobulin of claim 1, wherein the immunoglobulin comprises:

a light chain comprising an amino acid sequence of SEQ ID NO;

7.

3. The immunoglobulin of claim 1, wherein the amino acid substitution(s) in the Fc region are selected from L234W, L235I, L235Y, L235R, G236D, S267D, S267E, and L328F.

4. The immunoglobulin according to claim 1, wherein the amino acid substitution in the Fc region is S267E.

5. The immunoglobulin according to claim 1, wherein the amino acid substitution in the Fc region is L328F.

6. The immunoglobulin according to claim 1, wherein the amino acid substitution in the Fc region is S267E/L328F.

7. A pharmaceutical composition comprising the immunoglobulin according to claim 1, and a pharmaceutically acceptable carrier.

8. The immunoglobulin of claim 2, wherein the amino acid substitution(s) in the Fc region are selected from L234W, L235I, L235Y, L235R, G236D, S267D, S267E, and L328F.

9. The immunoglobulin according to claim 2, wherein the amino acid substitution in the Fc region is S267E.

10. The immunoglobulin according to claim 2, wherein the amino acid substitution in the Fc region is L328F.

11. The immunoglobulin according to claim 2, wherein the amino acid substitution in the Fc region is S267E/L328F.

12. A pharmaceutical composition comprising the immunoglobulin according to claim 2, and a pharmaceutically acceptable carrier.

13. The immunoglobulin 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, and G236N/S267E/L328F.

14. The immunoglobulin of claim 3, 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, and G236D/S267E/L328F.

15. The immunoglobulin of claim 8, 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, and G236D/S267E/L328F.

16. The immunoglobulin of claim 1, wherein the amino acid substitution in the Fc region is S267D.