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 fragment, 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 fragment of claim 1 , further comprising at least one human framework region adjacent to a complementarity determining region.
3. An isolated IL-23p19 antibody fragment, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:116.
4. An isolated IL-23p19 antibody fragment, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:106.
5. An isolated IL-23p19 antibody fragment, 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: 106.
6. An isolated IL-23p19 antibody fragment, comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:106 having up to three substitutions from residues 50-66 of the amino acid sequence of SEQ ID NO: 106.
7. An IL-23p19 antibody fragment according to claim 1 or 5 , 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.
8. An IL-23p19 antibody fragment according to claim 1 or 5 , wherein said antibody fragment 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.
9. A composition comprising the isolated IL-23p19 antibody fragment according to claim 1 or 5 and at least one pharmaceutically acceptable carrier or diluent.
10. The composition according to claim 9 , 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.
11. An IL-23p19 antibody fragment according to claim 1 or 5 , wherein the fragment is a Fab, Fab′, F(ab′) 2 , facb, pFc′, Fd, Fv or scFv.