Methods of treatment using an interferon gamma inhibitor
AssigneeAmgen Inc.
InventorsAndrew A. Welcher, Michael J. Boedigheimer, James B. Chung
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Abstract
The invention encompasses methods of treatment of interferon gamma (IFN-γ)-mediated diseases using IFN-γ inhibitors, such as anti-huIFN-γ antibodies, wherein levels of expression of one or more biomarkers are determined either before administration of the IFN-γ inhibitor and/or after administration. Also contemplated are methods of treatment using particular, pharmacodynamically effective doses of an anti-huIFN-γ antibody.
Claims29
A method for treating a patient suffering from an IFN-γ-mediated disease comprising administering to the patient a monoclonal anti-human interferon gamma (anti-huIFN-γ) antibody at a dose of 60 milligrams or 180 milligrams,
- wherein the anti-huIFN-γ antibody has a heavy chain complementarity determining region 1 (CDR1) comprising the amino acid sequence of SEQ ID NO:34, a heavy chain complementarity determining region 2 (CDR2) comprising the amino acid sequence of SEQ ID NO:35, a heavy chain complementarity determining region 3 (CDR3) comprising the amino acid sequence of SEQ ID NO:36, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:38, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:41, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:43.
A method for treating a patient having an IFN-γ-mediated disease comprising administering to the patient a therapeutically effective dose an anti-huIFN-γ antibody,
- wherein the anti-huIFN-γ antibody has a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:34, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:35, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:36, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:38, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:41, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:43, and
- wherein the level(s) of expression in a biological sample taken from the patient before administration of the antibody of one or more genes listed in Table 1, 2, 4, 5, and/or 6 at the RNA or protein level deviate from the level(s) of expression of the gene(s) in a control biological sample in a direction consistent with excess IFN-γ.
A method for treating a patient suffering from SLE, an inflammatory bowel disease, or psoriasis comprising:
- (a) taking a biological sample from the patient before administering a human anti-huIFN-γ antibody in step (b), wherein the level(s) of expression at the RNA or protein level in the biological sample from the patient of one or more of the genes in Table(s) 2, 4, 5, and/or 6 is determined;
- (b) administering to the patient a pharmacodynamically effective dose of the human anti-huIFN-γ antibody, wherein the antibody has a heavy chain complementarity determining region 1 (CDR1) comprising the amino acid sequence of SEQ ID NO:34, a heavy chain complementarity determining region 2 (CDR2) comprising the amino acid sequence of SEQ ID NO:35, a heavy chain complementarity determining region 3 (CDR3) comprising the amino acid sequence of SEQ ID NO:36, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:38, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:41, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:43;
- (c) taking a second biological sample taken from the patient after administration of the antibody, wherein the level(s) of expression of the gene(s) of step (a) in the second biological sample are determined;
- and
- (d) if the level(s) of expression of the gene(s) in the second biological sample determined in step (c), as compared to the level(s) of expression in the biological sample determined in step (a)
- (i) is modulated in a direction consistent with inhibition of IFN-γ, then continuing treatment of the patient with another pharmacodynamically effective dose of the antibody or
- (ii) is substantially the same as that in the biological sample of (a) or if the level of expression of the gene(s) in second biological sample of (c) deviates from the level of expression in the biological sample of (a) in a direction that is consistent with an excess of IFN-γ, then discontinuing treatment with the anti-human IFN-γ antibody.
Dependencies are inferred from the claim text.