Anti-IL-17A/IL-17F cross-reactive antibodies

• US 8,715,669 B2
• Filed: 12/28/2011
• Issued: 05/06/2014
• Est. Priority Date: 05/05/2008
• Status: Active Grant

• Current Assignee: Novimmune SA (Light Chain Bioscience AG)
• Original Assignee: Novimmune SA (Light Chain Bioscience AG)
• Inventors: Masternak, Krzysztof, Leger, Olivier
• Primary Examiner(s): Jiang, Dong
• Application Number:
  US13/339,110
• Publication Number:
  US 20120141492A1
• Time in Patent Office: 860 Days
• Field of Search: None
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• 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 2317/76 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

This invention provides fully human monoclonal antibodies that recognize IL-17F, the IL-17F homodimer, IL-17A, the IL-17A homodimer, and/or the heterodimeric IL-17A/IL-17F protein complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Claims

1. An isolated antibody, or an antigen-binding fragment thereof, that (1) binds IL-17A homodimer, IL-17F homodimer and IL-17A/IL-17F heterodimeric complex, and (2) exhibits (i) a binding affinity of at least 100 pM or less against the human IL-17A homodimer, (ii) a binding affinity of at least 300 pM or less against the human IL-17F homodimer, (iii) a binding affinity of at least 400 pM or less against the human IL-17A/IL-17F heterodimeric complex, (iv) a neutralizing ability of at least 40 nM or less against the human IL-17A homodimer, (v) a neutralizing ability of at least 120 nM or less against the human IL-17F homodimer, and (vi) a neutralizing ability of at least 31 nM or less against the human IL-17A/IL-17F heterodimeric complex, wherein the binding affinity is measured by surface plasmon resonance, and the neutralizing ability is determined by measuring IL-6 secretion by IL-17A, IL-17F or IL-17A/IL-17F heterodimeric complex-stimulated mouse or human embryonic fibroblasts.

2. The antibody or antibody fragment of claim 1, which binds IL-17A, IL-17F and the IL-17A/IL-17F heterodimeric complex and prevents one or more of IL-17F, IL-17A or the IL-17A/IL-17F heterodimeric complex from binding with its receptor.

3. The antibody or antibody fragment of claim 1, which is monoclonal.

4. The antibody or antibody fragment of claim 1, wherein the surface plasmon resonance is measured using a Biacore assay.

5. The antibody or antibody fragment of claim 4, wherein the Biacore assay is performed at 25°

C.

18. The antibody or antigen-binding fragment, of any one of claims 1, 6, 11 and 13, wherein the antibody fragment is selected from the group consisting of Fab, Fab′

, F(ab′

)₂, and Fv fragments, diabodies, and single-chain antibody molecules.

19. A pharmaceutical composition comprising the antibody or antibody fragment of claim 1, claim 6, claim 11, or claim 13, and a carrier.

6. An isolated antibody, or an antigen-binding fragment thereof, wherein the antibody comprises a VH CDR1 sequence comprising the amino acid sequence of SEQ ID NO:

85, a VH CDR2 sequence comprising the amino acid sequence of SEQ ID NO;

94, a VH CDR3 sequence comprising the amino acid sequence of SEQ ID NO;

95, a VL CDR1 sequence comprising the amino acid sequence of SEQ ID NO;

110, a VL CDR2 sequence comprising the amino acid sequence of SEQ ID NO;

97 and a VL CDR3 sequence comprising the amino acid sequence of SEQ ID NO;

111, wherein said antibody binds IL-17F and IL-17A.

7. The antibody or antibody fragment of claim 6, which binds IL-17A homodimer, IL-17F homodimer, and the IL-17A/IL-17F heterodimeric complex.

8. The antibody or antibody fragment of claim 6, which is an IgG isotype.

9. The antibody or antibody fragment of claim 6, which is an IgG1 isotype.

10. The antibody, or antigen-binding fragment, of claim 6, which is an IgG4 isotype.

11. The antibody or antibody fragment of claim 6, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:

54, and a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO;

40, wherein said antibody binds IL-17A homodimer, IL-17F homodimer and IL-17A/IL-17F heterodimeric complex.

12. The isolated antibody, or an antigen-binding fragment thereof, of claim 11, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO:

54 and a light chain variable region comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO;

40.

16. The antibody, or antigen-binding fragment, of claim 11 or 13, which is an IgG4 isotype.

17. The antibody or antibody fragment of any one of claims 2, 7, 11 and 13, which binds human IL-17A homodimer, IL-17F homodimer and human IL-17A/IL-17F heterodimeric complex.

13. An isolated antibody to IL-17A and IL-17F, or an antigen binding fragment thereof, wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

54, and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

40.

14. The antibody or antibody fragment of claim 13, which is an IgG isotype.

15. The antibody or antibody fragment of claim 13, which is an IgG1 isotype.