US2008161540A1PendingUtilityA1

IL-17A/F heterologous polypeptides and therapeutic uses thereof

58
Assignee: ARNOTT DAVID PPriority: Jul 8, 2003Filed: Dec 10, 2007Published: Jul 3, 2008
Est. expiryJul 8, 2023(expired)· nominal 20-yr term from priority
Inventors:David P. ArnottAustin GurneyPhilip E. HassJames LeeYan Wu
A61P 37/08A61P 7/06A61P 37/02A61P 5/00A61P 37/00A61P 7/00A61P 37/06A61P 9/00A61P 3/10A61P 29/00A61P 31/16A61P 31/22A61P 31/20A61P 31/12A61P 31/04A61P 25/00A61P 25/02A61P 27/16A61P 33/00A61P 31/10A61P 31/18A61P 1/16A61P 1/00A61P 19/02A61P 1/04A61P 21/00A61P 17/04A61P 13/12A61P 17/06A61P 19/00A61P 11/06A61P 17/00A61P 11/02A61P 11/00G01N 33/6869C07K 14/54C07K 2317/622C07K 2317/32C07K 2317/75C07K 2317/565C07K 2317/24C07K 2317/76C07K 2317/21A61K 38/00C07K 16/244C07K 2317/55C07K 2317/34C12N 15/11A61K 38/17C07K 16/00A61K 2039/505A61K 38/2073G01N 2800/24C07K 2317/92C07K 2319/40G01N 2500/10C07K 2317/31C07K 2317/33C07K 2319/30Y02A50/30
58
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The present invention is directed to a novel naturally occurring human cytokine that is comprised of a heterodimer of interleukin-17 and interleukin-17F designated herein as interleukin 17A/F (IL-17A/F). Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, specific antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

Claims

exact text as granted — not AI-modified
1 . An isolated antibody which specifically binds to a polypeptide having at least 80% amino acid sequence identity to: (a) the amino acid sequence of an IL-17A/F polypeptide comprising SEQ ID NO:3 and SEQ ID NO:4; or (b) the amino acid sequence of an IL-17A/F polypeptide comprising SEQ ID NO:3 and SEQ ID NO:4 lacking its associated signal peptides. 
     
     
         2 . The isolated antibody of  claim 1 , wherein said antibody is a monoclonal antibody, a humanized antibody or a single-chain antibody. 
     
     
         3 . The isolated antibody of  claim 1 , wherein said antibody is a monoclonal antibody, which preferably has nonhuman complementarity determining region (CDR) residues and human framework region (FR) residues. 
     
     
         4 . The isolated antibody of  claim 1  which is labeled and is immobilized on a solid support. 
     
     
         5 . The isolated antibody of  claim 1 , wherein said antibody is an antibody fragment, a monoclonal antibody, a single-chain antibody, or an anti-idiotypic antibody. 
     
     
         6 . The isolated antibody of  claim 5 , wherein the antibody fragment or single-chain antibody comprises a Fab fragment selected from the group consisting of the amino acid sequence shown in  FIG. 6  as SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, and SEQ ID NO:42, wherein said Fab fragment further comprises three heavy chain variable regions containing CDR-H1 consisting of amino acid residues 7 to 16 of SEQ ID NOs:9-42, CUR-H2 consisting of amino acid residues 30 to 46 of SEQ ID NOs:9-42, and CDR-H3 consisting of amino acid residue 78 to at least amino acid residue 96 of SEQ ID NOs:9-42, wherein said isolated Fab fragment is capable of binding IL-17A/F. 
     
     
         7 . The isolated antibody of  claim 5 , wherein the antibody fragment or single-chain antibody comprises a Fab fragment selected from the group consisting of the amino acid sequence shown in  FIG. 6  as SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, and SEQ ID NO:42, wherein said Fab fragment further comprises at least heavy chain variable region containing CDR-H1 consisting of amino acid residues 7 to 16 of SEQ ID NOs:9-42, and CDR-H2 consisting of amino acid residues 30 to 46 of SEQ ID NOs:9-42, wherein said Fab fragment is capable of binding IL-17A/F. 
     
     
         8 . The isolated antibody of  claim 5 , wherein the antibody fragment or single-chain antibody comprises a Fab fragment selected from the group consisting of the amino acid sequence shown in  FIG. 6  as SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, and SEQ ID NO:42, wherein said Fab fragment further comprises at least heavy chain variable regions containing CDR-H1 consisting of amino acid residues 7 to 16 of SEQ ID NOs:9-42 and CDR-H3 consisting of amino acid residue 78 to at least amino acid residue 9.6 of SEQ ID NOs:9-42, wherein said Fab fragment is capable of binding IL-17A/F. 
     
     
         9 . The isolated antibody of  claim 5 , wherein the antibody fragment or single-chain antibody comprises a Fab fragment selected from the group consisting of the amino acid sequence shown in  FIG. 6  as SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, and SEQ ID NO:42, wherein said Fab fragment further comprises at least heavy chain variable regions containing CDR-H2 consisting of amino acid residues 30 to 46 of SEQ ID NOs:9-42, and CDR-H3 consisting of amino acid residue 78 to at least amino acid residue 96 of SEQ ID NOs:9-42, wherein said Fab fragment is capable of binding IL-17A/F. 
     
     
         10 . The isolated antibody of  claim 5 , wherein the antibody fragment or single-chain antibody comprises a Fab fragment selected from the group consisting of the amino acid sequence shown in  FIG. 6  as SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, and SEQ ID NO:42, wherein said Fab fragment further comprises at least one of heavy chain variable region containing CDR-H1 consisting of amino acid residues 7 to 16 of SEQ ID NOs:9-42, CDR-H2 consisting of amino acid residues 30 to 46 of SEQ ID NOs:9-42, or CDR-H3 consisting of amino acid residue 78 to at least amino acid residue 96 of SEQ ID NOs:9-42, wherein said Fab fragment is capable of binding IL-17A/F. 
     
     
         11 . The isolated antibody of  claim 5 , wherein said CDR-H1 region of SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, or SEQ ID NO:42 comprises at least amino acid residues 7-10 corresponding to the amino sequence shown as SEQ ID NO:77, wherein said SEQ ID NO:77 is capable of binding IL-17A/F. 
     
     
         12 . The isolated antibody of  claim 5 , wherein said CDR-H2 region of SEQ ID NO:9, SEQ ID NO:10; SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, or SEQ ID NO:42 comprises at least amino acid residues 41-46 corresponding to amino acid sequence shown as SEQ ID NO:78), wherein said SEQ ID NO:78 is capable of binding IL-17A/F. 
     
     
         13 . The isolated antibody of  claim 5 , wherein said antibody is an anti-IL-17A/F agonist antibody. 
     
     
         14 . The isolated antibody of  claim 5 , wherein said antibody is an anti-IL-17A/F antagonist antibody. 
     
     
         15 . An isolated antibody capable of specifically binding to IL-17A comprising SEQ ID NO: 3 and IL-17F comprising SEQ ID NO: 4 wherein the IL-17A and IL-17F are in complex. 
     
     
         16 . An isolated antibody capable of specifically binding to IL-17A comprising SEQ ID NO: 3 or IL-17F comprising SEQ ID NO: 4 wherein the IL-17A and IL-17F are in a complex. 
     
     
         17 . An isolated antibody capable of specifically binding to IL-17A comprising SEQ ID NO: 3 wherein the IL-17A is in a complex. 
     
     
         18 . An isolated antibody capable of specifically binding to IL-17F comprising SEQ ID NO: 4 wherein the IL-17A is in a complex. 
     
     
         19 . The isolated antibody according to any one of  claims 15  to  18 , wherein the complex is a multimeric complex. 
     
     
         20 . The isolated antibody of  claim 19  wherein the multimeric complex is an IL-17F homodimer, an IL-17A homodimer, an IL-17F heterodimer, or an IL-17A heterodimer. 
     
     
         21 . The isolated antibody of  claim 20  wherein the IL-17F heterodimer or IL-17A heterodimer comprises IL-17A and IL-17F. 
     
     
         22 . The isolated antibody of  claim 21  wherein the IL-17A/F heterodimer comprises one molecule of IL-17A and one molecule of IL-17F joined by a covalent linkage.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.