ANTIBODIES TO RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS (RAGE) AND USES THEREOF

• US 20110104174A1
• Filed: 10/28/2010
• Published: 05/05/2011
• Est. Priority Date: 10/31/2009
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Strakhova, Marina I., Brederson, Jill-Desiree
• Granted Patent: US 8,420,083 B2
• Time in Patent Office: Days
• US Class Current: 424/143.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/90 characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present application relates to antibodies, such as monoclonal antibodies, and in particular CDR grafted, humanized versions thereof, for the treatment and diagnosis of pain and other neuroinflammatory conditions associated with the Receptor for Advanced Glycation End Products (RAGE).

Claims

1. A method for treating pain, comprising the step of administering to a mammal in need thereof an effective amount of a composition comprising an isolated monoclonal antibody comprising an antigen binding domain, said antibody capable of binding an epitope of a human RAGE molecule, said antigen binding domain comprising at least one CDR comprising an amino acid sequence selected from the group consisting of:

a) the CDR-H3 group of amino acid sequences consisting of SEQ ID NOs;

12 and 20;

modified CDR amino acid sequences having a sequence identity of at least 50% to one of said sequences; and

b) the CDR-L3 group of amino acid sequences consisting of SEQ ID NOs;

16 and 24; and

modified CDR amino acid sequences having a sequence identity of at least 50% to one of said sequences.

2. The method according to claim 1, wherein the antibody further comprises at least one CDR comprising an amino acid sequence selected from the CDR-H1 group consisting of SEQ ID NOs:

10 and 18;

or selected from the CDR-H2 group consisting of SEQ ID NOs;

11, 19;

or selected from the CDR-L1 group consisting of SEQ ID NOs;

14 and 22;

or selected from the CDR-L2 group consisting of SEQ ID NOs;

15 and 23; and

modified CDR amino acid sequences having a sequence identity of at least 50% to one of said sequences.

3. The method according to claim 2, wherein the antibody further comprises at least 3 CDRs which are selected from a variable domain CDR set comprising:

4. The method according to claim 1, wherein the antibody further comprises a human acceptor framework.

5. The method of claim 1, wherein the antibody comprises at least one heavy chain variable domain selected from the group consisting of:

SEQ ID NOs;

56 and 57, at least one light chain variable domain selected from the group consisting of;

SEQ ID NOs;

58 and 59 or combinations thereof.

6. The method according to claim 5, wherein said binding protein comprises (a) at least one heavy chain framework mutation at a position selected from the group consisting of:

1, 2, 68, 70, 72, 76, 85, 89 and 95;

(b) at least one light chain framework mutation at a position selected from the group consisting of;

11, 13, 43, 49, 58, 70 and 87;

or (c) combinations of (a) and (b).

7. The method of claim 1, wherein the antibody comprises (a) at least one framework mutation at a position selected from the group consisting of:

62, 67, 68 and 69;

(b) at least one light chain framework mutation at a position selected from the group consisting of;

63, 64, 65 and 66;

or (c) combinations of (a) and (b).

8. The method of claim 1, wherein the antibody is selected from the group consisting of antibodies 11E6 and 4E5.

9. The method of claim 1, wherein the composition comprises a formulation, wherein said formulation comprises the antibody of claim 1 in crystallized form as an ingredient;

and at least one polymeric carrier.

10. The method of claim 8, wherein the antibody is 11E6.

11. The method of claim 1, wherein said pain is selected from the group consisting of chronic and acute pain.

12. The method of claim 1, wherein said pain is selected from the group consisting of:

peripheral or central neuropathic pain, nociceptive pain; and

psychogenic pain.

13. The method of claim 1, wherein said pain is nociceptive pain or psychogenic pain.

14. The method of claim 1, wherein said pain is neuropathic pain.

15. The method of claim 14, wherein said neuropathic pain is peripheral or central neuropathic pain.

16. The method of claim 1, wherein said pain is inflammatory pain.

17. A monoclonal antibody as defined in claim 1 for use in treating pain.