IL-17 AND IL-23 ANTAGONISTS AND METHODS OF USING THE SAME

• US 20110059087A1
• Filed: 08/27/2010
• Published: 03/10/2011
• Est. Priority Date: 06/13/2006
• Status: Active Grant

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Inventors: Mabry, Robert, Meengs, Brent, West, James W., Levin, Steven D., Presnell, Scott R., Lewis, Katherine E.
• Granted Patent: US 8,227,579 B2
• Time in Patent Office: Days
• US Class Current: 424/135.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-17, IL-23 via it'"'"'s p19 subunit or both IL-17 and IL-23 (via p19). IL-17 and IL-23 are cytokines that are involved in inflammatory processes and human disease.

Claims

1. An isolated antibody or antibody fragment that specifically binds a polypeptide comprising SEQ ID NO:

2, wherein the antibody binds an epitope selected from the group consisting of;

a) an epitope comprising amino acid residues 34 to 41 of SEQ ID NO;

2; and

b) an epitope comprising amino acid residues 52 to 64 of SEQ ID NO;

2.

2. The antibody fragment of claim 1, wherein the antibody fragment is selected from the group consisting of:

a) a F(ab′

)₂;

b) a F(ab)₂;

c) a Fab′

;

d) a Fab;

e) a Fv; and

f) a scFv.

3. The antibody or antibody fragment of claim 1, wherein the antibody or antibody fragment is a bispecific antibody.

4. An isolated antibody or antibody fragment that binds a polypeptide comprising SEQ ID NO:

2, wherein the antibody binds an epitope comprising amino acid residues 77 to 85 of SEQ ID NO;

2.

5. The antibody fragment of claim 4, wherein the antibody fragment is selected from the group consisting of:

a) a F(ab′

)₂;

b) a F(ab)₂;

c) a Fab′

;

d) a Fab;

e) a Fv; and

f) a scFv.

6. The antibody or antibody fragment of claim 4, wherein the antibody or antibody fragment is a bispecific antibody.

7. An isolated antibody that binds a polypeptide consisting of the amino acid sequence of SEQ ID NO:

4, wherein the antibody binds an epitope selected from the group consisting of;

a) an epitope comprising amino acid residues 55 to 66 of SEQ ID NO;

4; and

b) an epitope comprising amino acid residues 74 to 85 of SEQ ID NO;

4.

8. The antibody fragment of claim 7, wherein the antibody fragment is selected from the group consisting of:

a) a F(ab′

)₂;

b) a F(ab)₂;

c) a Fab′

;

d) a Fab;

e) a Fv; and

f) a scFv.

9. The antibody or antibody fragment of claim 7, wherein the antibody or antibody fragment is a bispecific antibody.

10. An isolated antibody that binds a polypeptide comprising the amino acid sequence of SEQ ID NO:

4, wherein the antibody binds an epitope selected from the group consisting of;

a) an epitope comprising amino acid residues 137 to 146 of SEQ ID NO;

4; and

b) an epitope comprising amino acid residues 155 to 164 of SEQ ID NO;

4.

11. The antibody fragment of claim 10, wherein the antibody fragment is selected from the group consisting of:

a) a F(ab′

)₂;

b) a F(ab)₂;

c) a Fab′

;

d) a Fab;

e) a Fv; and

f) a scFv.

12. The antibody or antibody fragment of claim 10, wherein the antibody or antibody fragment is a bispecific antibody.

13. An bispecific antibody comprising a first antigen binding site and a second antigen binding site, wherein the first antigen binding site comprises an antibody or antibody fragment that competes with an antibody selected from the group consisting of:

a) an antibody comprising a light chain comprising SEQ ID NO;

92 and a heavy chain comprising SEQ ID NO;

93;

b) an antibody comprising a light chain comprising SEQ ID NO;

80 and a heavy chain comprising SEQ ID NO;

81;

c) an antibody comprising a light chain comprising SEQ ID NO;

128 and a heavy chain comprising SEQ ID NO;

129;

d) an antibody comprising a light chain comprising SEQ ID NO;

144 and a heavy chain comprising SEQ ID NO;

145;

e) an antibody comprising a light chain comprising SEQ ID NO;

136 and a heavy chain comprising SEQ ID NO;

137;

f) an antibody comprising a light chain comprising SEQ ID NO;

96 and a heavy chain comprising SEQ ID NO;

97;

g) an antibody comprising a light chain comprising SEQ ID NO;

100 and a heavy chain comprising SEQ ID NO;

101;

h) a light chain comprising SEQ ID NO;

124 and a heavy chain comprising SEQ ID NO;

125;

i) an antibody comprising a light chain comprising SEQ ID NO;

132 and a heavy chain comprising SEQ ID NO;

133;

j) an antibody comprising a light chain comprising SEQ ID NO;

108 and a heavy chain comprising SEQ ID NO;

109; and

k) an antibody comprising a light chain comprising the light chain CDR1, CDR2, and CDR3 of any of a)-j), above and a heavy chain comprising the heavy chain CDR1, CDR2, and CDR3 of a)-j), above

or competes with an antibody comprising a light chain comprising SEQ ID NO;

148 and a heavy chain comprising SEQ ID NO;

149.

for specifically binding a polypeptide consisting of the amino acid sequence of SEQ ID NO;

2;

and wherein the second antigen binding site comprises an antibody or antibody fragment that competes with an antibody selected from the group consisting of;

a) an antibody comprising a light chain comprising SEQ ID NO;

768 and a heavy chain comprising SEQ ID NO;

769; and

b) an antibody comprising a light chain comprising SEQ ID NO;

764 and a heavy chain comprising SEQ ID NO;

765;

or competes with an antibody selected from the group consisting of;

a) an antibody comprising a light chain comprising SEQ ID NO;

774 and a heavy chain comprising SEQ ID NO;

775; and

b) an antibody comprising a light chain comprising SEQ ID NO;

776 and a heavy chain comprising SEQ ID NO;

777;

for specifically binding a polypeptide consisting of the amino acid sequence of SEQ ID NO;

2.

14. An antibody or antibody fragment that binds a polypeptide comprising SEQ ID NO:

4, wherein the antibody competes for binding with an antibody comprising a light chain comprising SEQ ID NO;

1014 and a heavy chain comprising SEQ ID NO;

1015 for specifically binding the polypeptide consisting of the amino acid sequence of SEQ ID NO;

4.

15. The antibody or antibody fragment of claim 14, wherein the antibody or antibody fragment is a bispecific antibody.

16. A method for inhibiting interleukin-17A (IL-17A) production by T cells comprising treating said T cells with a bispecific antibody comprising a first antigen binding site that specifically binds IL-17A and a second antigen binding site that specifically binds IL-23p19.

17. A method for preventing, inhibiting, or reducing relapse in multiple sclerosis comprising administering a bispecific antibody comprising a first antigen binding site that specifically binds IL-17A and a second antigen binding site that specifically binds IL-23p19.

18. The method of claim 17, wherein the bispecific antibody is a scFv molecule.

19. A method for preventing, inhibiting, or reducing IBD comprising administering a bispecific antibody comprising a first antigen binding site that specifically binds IL-17A and a second antigen binding site that specifically binds IL-23p19.

20. The method of claim 19, wherein the bispecific antibody is a scFv molecule.