Human anti-IL-23 antibodies, compositions, methods and uses
A human anti-IL-23p19 antibody, including isolated nucleic acids that encode at least one anti-IL-23p19 antibody, vectors, host cells, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.
1. An isolated IL-23p19 antibody, comprising a light chain variable region and a heavy chain variable region, said light chain variable region comprising:
a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:50;
a CDRL2 amino acid sequence of SEQ ID NO:56; and
a CDRL3 amino acid sequence of SEQ ID NO:73,
said heavy chain variable region comprising:
a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:5;
a CDRH2 amino acid sequence of SEQ ID NO:20; and
a CDRH3 amino acid sequence of SEQ ID NO:44.
2. The isolated IL-23p19 antibody of claim 1 , further comprising at least one human framework region adjacent to a complementarity determining region.
3. An isolated IL-23p19 antibody, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:116.
4. An isolated IL-23p19 antibody, comprising a heavy chain variable region comprising e amino acid sequence of SEQ ID NO:105.
5. An isolated IL-23p19 antibody, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:116 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 105.
6. An isolated IL-23p19 antibody, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:105 having up to three substitutions from residues 50-66 of the amino acid sequence of SEQ ID NO: 105.
7. An isolated IL-23p19 antibody, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 116 and the heavy chain variable region of claim 6 .
8. An IL-23p19 antibody according to any of claims 1 , 2 , 3 - 5 , 6 and 7 wherein said antibody binds IL-23p19 with at least one affinity selected from at least 10 M, at least 10 −10 M, at least 10 −11 M, and at least 10 −12 M, at least 10 −13 M, at least 10 −14 M, and at least 10 −15 M, as determined by surface plasmon resonance or the Kinexa method.
9. An IL-23p19 antibody according to any of claims 1 , 2 , 3 - 5 , 6 and 7 , wherein said antibody substantially modulates an activity of the IL-23 polypeptide, the activity selected from the group consisting of binding to the IL-23 receptor (IL-23R), induction of STAT3 phosphorylation, and IL-17 production.
10. A composition comprising the isolated IL-23p19 antibody according to claim 9 and at least one pharmaceutically acceptable carrier or diluent.
11. The composition according to claim 10 , further comprising at least one compound or polypeptide selected from, a TNF antagonist, an anti-infective drug, a cardiovascular (CV) system drug, a central nervous system (CNS) drug, an autonomic nervous system (ANS) drug, a respiratory tract drug, a gastrointestinal (GI) tract drug, a hormonal drug, a drug for fluid or electrolyte balance, a hematologic drug, an antineoplastic, an immunomodulation drug, an ophthalmic drug, an otic drug or nasal drug, a topical drug, a nutritional drug, and a cytokine antagonist.
12. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of an IL-23p19 antibody according to any of claims 1 , 2 , 3 - 5 , 6 and 7 .
13. The article of manufacture of claim 12 , wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
14. An isolated IL-23p19 antibody, comprising a light chain variable region amino acid sequence encoded by the nucleotide sequence selected from the group consisting of SEQ ID NOS:142-144.
15. An isolated IL-23p19 antibody, comprising a heavy chain variable region amino acid sequence encoded by the nucleotide sequence selected from the group consisting of SEQ ID NOS:139-141.
16. An isolated IL-23p19 antibody, comprising the light chain variable region sequence of claim 14 and a heavy chain variable region amino acid sequence encoded by the nucleotide sequence selected from the group consisting of SEQ ID NOS:139-141.
17. The IL-23p19 antibody according to claim 16 , wherein said antibody binds IL-23p19 with at least one affinity selected from at least 10 −9 M, at least 10 −10 M, at least 10 −11 M, and at least 10 −12 M, at least 10 −13 M, at least 10 −14 M, and at least 10 −15 M, as determined by surface plasmon resonance or the Kinexa method.
18. The IL-23p19 antibody according to claim 16 , wherein said antibody substantially modulates an activity of the IL-23 polypeptide, the activity selected from the group consisting of binding to the IL-23 receptor (IL-23R), induction of STAT3 phosphorylation, and IL-17 production.
19. A composition comprising the isolated IL-23p19 antibody according to claim 16 and at least one pharmaceutically acceptable carrier or diluent.
20. A composition according to claim 19 , further comprising at least one compound or polypeptide selected from a TNF antagonist, an anti-infective drug, a cardiovascular (CV) system drug, a central nervous system (CNS) drug, an autonomic nervous system (ANS) drug, a respiratory tract drug, a gastrointestinal (G1) tract drug, a hormonal drug, a drug for fluid or electrolyte balance, a hematologic drug, an antineoplastic, an immunomodulation drug, an ophthalmic drug, an otic drug or nasal drug, a topical drug, a nutritional drug, and a cytokine antagonist.
21. An article of manufacture for human pharmaceutical or diagnostic use, comprising packaging material and a container comprising a solution or a lyophilized form of the IL-23p19 antibody according to claim 16 .
22. The article of manufacture of claim 21 , wherein said container is a component of a parenteral, subcutaneous, intramuscular, intravenous, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, intralesional, bolus, vaginal, rectal, buccal, sublingual, intranasal, or transdermal delivery device or system.
23. The composition according to claim 10 , wherein the antibody is conjugated to a detectable label or reporter.
24. The composition according to claim 19 , wherein the antibody is conjugated to a detectable label or reporter.