INTERLEUKIN-17 (IL-17) ANTAGONISTIC ANTIBODIES
An Interleukin-17 (IL-17) binding molecule, in particular an antibody to human IL-17, more preferably a human antibody to human IL-17 is provided, wherein the hypervariable regions of the heavy and light chains have amino acid sequences as defined, for use in the treatment of an IL-17 mediated disease or disorder, e.g. rheumatoid arthritis.
1 . A method of treating an Interleukin-17 (IL-17)-mediated disease or disorder, comprising administering an effective amount of a monoclonal anti-IL-17 antibody or antigen-binding thereof to a patient in need thereof, wherein the anti-IL-17 antibody or antigen-binding thereof is produced by a process comprising:
a) culturing a recombinant host cell comprising:
i) a nucleic acid that encodes an antibody heavy chain variable domain (V H ) comprising, in sequence:
a complementarity determining region (CDR) 1 having the amino acid sequence set forth as SEQ ID NO:1, a CDR2 having the amino acid sequence set forth as SEQ ID NO:2, and a CDR3 having the amino acid sequence set forth as SEQ ID NO:3; or
a CDR1-x having the amino acid sequence set forth as SEQ ID NO:11, a CDR2-x having the amino acid sequence set forth as SEQ ID NO:12, and a CDR3-x having the amino acid sequence set forth as SEQ ID NO:13; and
ii) a nucleic acid that encodes an antibody light chain variable domain (V L ) comprising, in sequence, a CDR1′ having the amino acid sequence set forth as SEQ ID NO:4, a CDR2′ having the amino acid sequence set forth as SEQ ID NO:5, and a CDR3′ having the amino acid sequence set forth as SEQ ID NO:6,
under conditions sufficient to express the anti-IL-17 antibody or antigen-binding fragment thereof; and
b) recovering the anti-IL-17 antibody or antigen-binding fragment thereof from the host cell culture.
2 . The method according to claim 1 , wherein the recombinant host cell comprises:
i) a nucleic acid that encodes an antibody V H comprising the amino acid sequence set forth as SEQ ID NO:8; and
ii) a nucleic acid that encodes an antibody V L comprising the amino acid sequence set forth as SEQ ID NO:10.
3 . The method according to claim 2 , wherein the anti-IL-17 antibody or antigen-binding fragment thereof is a human antibody.
4 . The method according to claim 3 , wherein the anti-IL-17 antibody or antigen-binding fragment thereof is a human antibody of the IgG1/κ isotype.
5 . The method according to claim 4 , wherein the anti-IL-17 antibody or antigen-binding fragment thereof has an IC 50 of about 5 nM or less for inhibition of Interleukin-6 (IL-6) production induced by 1 nM human IL-17 in human dermal fibroblasts.
6 . The method according to claim 4 , wherein the anti-IL-17 antibody or antigen-binding fragment thereof has a K D for binding to human IL-17 of about 122 pM±22 pM as determined by surface plasmon resonance.
7 . The method according to claim 4 , wherein the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof is administered to the patient at a dosage from about 0.05 mg/kg—about 10 mg/kg.
8 . The method according to claim 7 , wherein the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof is administered to the patient once per week, once every 2 weeks, once every 4 weeks, once every 8 weeks, once every 10 weeks, once every month, once every 2 months, or once every 3 months.
9 . The method according to claim 8 , wherein the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof is administered to the patient parenterally, intravenously, intramuscularly, or subcutaneously.
10 . The method according to claim 9 , further comprising administering, concomitantly or in sequence, a therapeutically effective amount of at least one second drug substance selected from an immuno-suppressive drug, an immunomodulatory drug, an anti-inflammatory drug, a chemotherapeutic drug or an anti-infectious drug.
11 . The method according to claim 4 , wherein the monoclonal anti-IL-17 antibody or antigen-binding fragment thereof is administered monthly to the patient subcutaneously as part of a liquid pharmaceutical composition at a dosage of about 0.1 mg/kg-about 5 mg/kg, wherein the patient has psoriatic arthritis, ankylosing spondylitis, or psoriasis.
12 . A monoclonal anti-IL-17 antibody or antigen-binding thereof, wherein the anti-IL-17 antibody or antigen-binding thereof is produced by a process comprising:
a) culturing a recombinant host cell comprising:
i) a nucleic acid that encodes an antibody heavy chain variable domain (V H ) comprising, in sequence:
a complementarity determining region (CDR) 1 having the amino acid sequence set forth as SEQ ID NO:1, a CDR2 having the amino acid sequence set forth as SEQ ID NO:2, and a CDR3 having the amino acid sequence set forth as SEQ ID NO:3; or
a CDR1-x having the amino acid sequence set forth as SEQ ID NO:11, a CDR2-x having the amino acid sequence set forth as SEQ ID NO:12, and a CDR3-x having the amino acid sequence set forth as SEQ ID NO:13; and
ii) a nucleic acid that encodes an antibody light chain variable domain (V L ) comprising, in sequence, a CDR1′ having the amino acid sequence set forth as SEQ ID NO:4, a CDR2′ having the amino acid sequence set forth as SEQ ID NO:5, and a CDR3′ having the amino acid sequence set forth as SEQ ID NO:6,
under conditions sufficient to express the anti-IL-17 antibody or antigen-binding fragment thereof; and
b) recovering the anti-IL-17 antibody or antigen-binding fragment thereof from the host cell culture.
13 . A process for producing a monoclonal anti-IL-17 antibody or antigen-binding thereof, comprising:
a) culturing a recombinant host cell comprising:
i) a nucleic acid that encodes an antibody heavy chain variable domain (V H ) comprising, in sequence:
a complementarity determining region (CDR) 1 having the amino acid sequence set forth as SEQ ID NO:1, a CDR2 having the amino acid sequence set forth as SEQ ID NO:2, and a CDR3 having the amino acid sequence set forth as SEQ ID NO:3; or
a CDR1-x having the amino acid sequence set forth as SEQ ID NO:11, a CDR2-x having the amino acid sequence set forth as SEQ ID NO:12, and a CDR3-x having the amino acid sequence set forth as SEQ ID NO:13; and
ii) a nucleic acid that encodes an antibody light chain variable domain (V L ) comprising, in sequence, a CDR1′ having the amino acid sequence set forth as SEQ ID NO:4, a CDR2′ having the amino acid sequence set forth as SEQ ID NO:5, and a CDR3′ having the amino acid sequence set forth as SEQ ID NO:6,
under conditions sufficient to express the anti-IL-17 antibody or antigen-binding fragment thereof; and
b) recovering the anti-IL-17 antibody or antigen-binding fragment thereof from the host cell culture.