ANTIBODIES TO IL-6 AND USE THEREOF

• US 20120142900A1
• Filed: 10/20/2011
• Published: 06/07/2012
• Est. Priority Date: 05/21/2007
• Status: Abandoned Application

• Current Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Original Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Inventors: Garcia-Martinez, Leon, Jensen, Anne Elisabeth Carvalho, Olson, Katie, Dutzar, Ben, Ojala, Ethan, Kovacevich, Brian, Latham, John, Smith, Jeffrey T. L.
• Application Number:
  US13/277,390
• Publication Number:
  US 20120142900A1
• Time in Patent Office: Days
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• 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 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• 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 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention relates to anti-IL-6 antibodies and antibody fragments having a particular epitopic specificity. These antibodies and antibody fragments have clinical therapeutic and diagnostic applications in treating and detecting disease conditions wherein Il-6 levels are elevated.

Claims

1-153. -153. (canceled)

154. An anti-human Il-6 antibody or antibody fragment that specifically competes with an anti-human IL-6 antibody comprising the variable light and heavy chains in SEQ ID NO:

2 and 3 respectively, wherein said competition can be detected in a competitive binding assay using said antibody or antibody fragment, the human Il-6 polypeptide in SEQ ID NO;

1, and an anti-human IL-6 antibody comprising the variable light and heavy sequences contained in SEQ ID NO;

2 and 3 respectively.

156. The antibody or fragment of claim 154, which blocks the interaction of human Il-6 with Il-6R1 and an 130.

158. The antibody or fragment of claim 154, which is selected from chimeric antibodies, humanized antibodies, humanized antibodies, human antibodies, rabbit antibodies, and single chain antibodies.

160. The antibody or fragment of claim 154, which is selected from scFvs, camelbodies, nanobodies, IgNAR, small modular immunopharmaceuticals (SMIPs), Fab, Fab′

, and F(ab′

) fragments.

162. The antibody or fragment of claim 154, which contains human constant regions selected from IgG1, IgG2, IgG3, IgG4, IgG5, IgG6, IgG7, IgG8, IgG9, IgG10, IgG11, IgG12, IgG13, IgG14, IgG15, IgG16, IgG17, IgG18 and IgG19 constant regions.

164. The antibody or fragment of claim 154, which contains human IgG1 or IgG3 constant regions.

166. The antibody or fragment of claim 154, which is substantially non-glycosylated.

155. An anti-human Il-6 antibody or antibody fragment that specifically competes with the epitope bound by an anti-human IL-6 antibody comprising the variable light and heavy chains in SEQ ID NO:

2 and 3 respectively, wherein said competition can be detected in a competitive binding assay using said antibody or antibody fragment, the human II-6 polypeptide in SEQ ID NO;

1, and an anti-human IL-6 antibody comprising the variable light and heavy sequences contained in SEQ ID NO;

2 and 3 respectively, and further wherein said anti-human Il-6 antibody or fragment when used in a western immunoblot assay that detects binding of the antibody or fragment to peptides comprised in a library of 57 overlapping polypeptides which each are 15 amino acids i length corresponding to the entirety of the human Il-6 polypeptide in SEQ ID NO;

1, wherein said 57 peptides are those in SEQ ID NO;

590-645 inclusive, specifically binds to the same peptides in said libray as an anti-human Il-6 antibody or fragment comprising the variable light and heavy sequences in SEQ ID NO;

2 and 3 respectively, wherein specific binding of the antibody or fragment is detected using a chemiluminescent label which emits a detectable chemiluminescent signal when specific binding of the antibody or fragment to a peptide in the library occurs.

157. The antibody or fragment of claim 155, which blocks the interaction of human Il-6 with Il-6R1 and gp130.

159. The antibody or fragment of claim 155, which is selected from chimeric antibodies, humanized antibodies, humanized antibodies, human antibodies, rabbit antibodies, single chain antibodies.

161. The antibody or fragment of claim 155, which is selected from scFvs, camelbodies, nanobodies, IgNAR, small modular immunopharmaceuticals (SMIPs), Fab, Fab′

, and F(ab′

) fragments.

163. The antibody or fragment of claim 155, which contains human constant regions selected from IgG1, IgG2, IgG3, IgG4, IgG5, IgG6, IgG7, IgG8, IgG9, IgG10, IgG11, IgG12, IgG13, IgG14, IgG15, IgG16, IgG17, IgG18 and IgG19 constant regions.

165. The antibody or fragment of claim 155, which contains human IgG1 or IgG3 constant regions.

167. The antibody or fragment of claim 155, which is substantially non-glycosylated.