Compounds
AssigneeMedImmune, LLC
InventorsSimon Charles Cruwys, Steven Godfrey Lane, Philip Mallinder
Life of this patent
Estimating the term…
Abstract
Binding members, e.g. human antibody molecules, which bind interleukin-6 (IL-6) and neutralise its biological effects. Use of binding members for IL-6 in medical treatment e.g. for treating inflammatory diseases and tumours associated with IL-6.
Claims67
An isolated binding member for human IL-6, which binds human IL-6 with a KD of not more than 30 pM as defined by surface plasmon resonance.
An isolated binding member for human IL-6, which binds human IL-6 at residue Phe102 and/or Ser204, the residue numbering being defined according to the full length human IL-6 amino acid sequence SEQ ID NO:
- 161.
An isolated binding member for human IL-6, wherein the binding member has an IC50 of less than 1 nM in an assay of inhibition of VEGF release from human synovial fibroblasts stimulated with 0.6 pM human IL-1β and 2.4 nM soluble human IL-6Rα.
An isolated binding member for human IL-6, comprising a set of CDRs:
- HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the set of CDRs has 22 or fewer amino acid alterations from a set of CDRs in which:
- HCDR1 has amino acid sequence SEQ ID NO:
- 3;
- HCDR2 has amino acid sequence SEQ ID NO:
- 4;
- HCDR3 has amino acid sequence SEQ ID NO:
- 115;
- LCDR1 has amino acid sequence SEQ ID NO:
- 8;
- LCDR2 has amino acid sequence SEQ ID NO:
- 9;
- and
- LCDR3 has amino acid sequence SEQ ID NO:
- 120, and wherein
- the binding member has an IC50 of less than 100 pM in an assay for inhibition of proliferation of TF-1 cells in response to 20 pM human IL-6.
An isolated binding member for human IL-6, comprising an HCDR3, an LCDR3 and/or a set of CDRs of any of antibodies 2, 3, 4, 5, 7, 8, 10, 14, 16, 17, 18, 19, 21, 22 or 23.
An isolated antibody molecule comprising a heavy chain comprising amino acid sequence SEQ ID NO:
- 112 and a light chain comprising amino acid sequence SEQ ID NO:
- 117.
An isolated antibody molecule that binds IL-6, wherein the antibody molecule comprises a VH domain amino acid sequence at least 90% identical to SEQ ID NO:
- 112 and a VL domain amino acid sequence at least 90% identical to SEQ ID NO:
- 117.
42-48. (canceled)
A method for producing an antibody antigen-binding domain for IL-6, the method comprising
- providing, by way of addition, deletion, substitution or insertion of one or more amino acids in the amino acid sequence of a parent VH domain comprising HCDR1, HCDR2 and HCDR3, wherein the parent VH domain HCDR1, HCDR2 and HCDR3 are a set of HCDRs as shown in Table 7, a VH domain which is an amino acid sequence variant of the parent VH domain, and optionally combining the VH domain thus provided with one or more VL domains to provide one or more VH/VL combinations;
- and
- testing said VH domain which is an amino acid sequence variant of the parent VH domain or the VH/VL combination or combinations to identify an antibody antigen binding domain for IL-6.
A method for producing a binding member that binds IL-6, which method comprises:
- providing starting nucleic acid encoding a VH domain or a starting repertoire of nucleic acids each encoding a VH domain, wherein the VH domain or VH domains either comprise a HCDR1, HCDR2 and/or HCDR3 to be replaced or lack a HCDR1, HCDR2 and/or HCDR3 encoding region;
- combining said starting nucleic acid or starting repertoire with donor nucleic acid or donor nucleic acids encoding or produced by mutation of the amino acid sequence of an HCDR1, HCDR2, and/or HCDR3 shown in Table 7, such that said donor nucleic acid is or donor nucleic acids are inserted into the CDR1, CDR2 and/or CDR3 region in the starting nucleic acid or starting repertoire, so as to provide a product repertoire of nucleic acids encoding VH domains;
- expressing the nucleic acids of said product repertoire to produce product VH domains;
- optionally combining said product VH domains with one or more VL domains;
- selecting a binding member for IL-6, which binding member comprises a product VH domain and optionally a VL domain;
- and
- recovering said binding member or nucleic acid encoding it.
Dependencies are inferred from the claim text.