Anti-IL-23 antibodies
An anti-IL-23 antibody, including isolated nucleic acids that encode at least one anti-IL-23 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof have applications in diagnostic and/or therapeutic compositions, methods and devices.
1. An isolated IL-23p19 antibody fragment, wherein said antibody fragment binds to human IL-23p19 at one or more regions of human IL-23p19 consisting of the amino acid residues selected from the group consisting of residues 93-102, 93-110, and 127-137 of SEQ ID NO:1.
2. The isolated antibody fragment of claim 1 , wherein said antibody fragment is selected from the group consisting of rodent, chimeric, humanized, and human.
3. An isolated antibody that competitively binds to IL-23p19 with the isolated IL-23p19 antibody fragment of claim 1 .
4. The IL-23p19 antibody fragment of claim 1 , wherein said antibody fragment 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.
5. The IL-23p19 antibody fragment of claim 4 , wherein said antibody fragment binds IL-23p19 with an affinity between about 3.38×10 −10 M and about 4.3×10 −11 M, as determined by surface plasmon resonance.
6. The IL-23-p19 antibody fragment of claim 4 , wherein said antibody fragment substantially downregulates an activity of the IL-23 polypeptide comprising SEQ ID NO:1, the activity being selected from the group consisting of binding to the IL-23 receptor (IL-23R), induction of STAT3 phosphorylation, and IL-17 production.
7. An isolated IL-23p19 antibody fragment, comprising a light chain variable region comprising:
a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:9;
a CDRL2 amino acid sequence of SEQ ID NO:10; and
a CDRL3 amino acid sequence of SEQ ID NO:11,
or a heavy chain variable region comprising:
a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:4;
a CDRH2 amino acid sequence of SEQ ID NO:5; and
a CDRH3 amino acid sequence of SEQ ID NO:6.
8. The isolated IL-23p19 antibody fragment of claim 7 , comprising a light chain variable region amino acid sequence of SEQ ID NO:8.
9. The isolated IL-23p19 antibody fragment of claim 7 , comprising a heavy chain variable region amino acid sequence of SEQ ID NO:3.
10. An isolated antibody fragment of any one of claim 8 or 9 , wherein said antibody light chain variable region is at least one of chimerized, humanized, or CDR-grafted.
11. A composition comprising an isolated IL-23p19 antibody fragment of any one of claim 1 or 3 , and at least one pharmaceutically acceptable carrier or diluent.
12. The composition of claim 11 , further comprising a compound or polypeptide selected from the group consisting of a detectable label or reporter, 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 opthalmic, otic or nasal drug, a topical drug, a nutritional drug, a cytokine, and a cytokine antagonist.
13. An isolated antibody fragment of any one of claim 1 , 3 or 10 , wherein said fragment is selected from the group consisting of a Fab, Fab', F(ab′) 2 , pFc, Fd, Fv, scFv, and fragments thereof.