Methods, compositions and dosing regimens for treating or preventing interferon-gamma related indications
The disclosure relates generally to methods compositions and dosing regimens for treating, preventing and/or delaying the onset or progression of, or alleviating a symptom associated with elevated IFN-γ levels.
1. An injectable pharmaceutical formulation comprising:
a) 5 mg/mL of a fully human anti-interferon gamma (IFNγ) monoclonal antibody; and
b) 1.55 mg/mL L-histidine, 3.14 mg/mL L-histidine monohydrochloride, monohydrate, 0.05 mg/mL Polysorbate 80, and 7.31 mg/mL sodium chloride (NaCl),
wherein the pH is between 5.8 and 6.2, and
wherein the antibody comprises a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SYAMS (SEQ ID NO: 1); a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of AISGSGGSTYYADSVKG (SEQ ID NO: 2); and a variable heavy chain complementarity determining region 3 (VH CDR3) comprising the amino acid sequence of DGSSGWYVPHWFDP (SEQ ID NO: 3); a variable light chain complementarity determining region 1 (VL CDR1) comprising the amino acid sequence of TRSSGSIASNYVQ (SEQ ID NO: 4); a variable light chain complementarity determining region 2 (VL CDR2) region comprising the amino acid sequence of EDNQRPS (SEQ ID NO: 5); and a variable light chain complementarity determining region 3 (VL CDR3) region comprising the amino acid sequence of QSYDGSNRWM (SEQ ID NO: 6).
2. The formulation of claim 1 , wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 47, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48.
3. A method of treating a condition in a human subject by administering the formulation of claim 1 , wherein the condition is primary hemophagocytic lymphohistiocytosis (HLH) or secondary HLH.
4. The method of claim 3 , wherein the human subject is pediatric or adult.
5. A unit dose vial comprising, 2 ml or 10 ml of a fully human anti-interferon gamma (IFNγ) monoclonal antibody solution suitable for injection,
wherein the solution comprises 1.55 mg/mL L-histidine, 3.14 mg/mL L-histidine monohydrochloride, monohydrate, 0.05 mg/mL Polysorbate 80, and 7.31 mg/mL sodium chloride (NaCl),
wherein the antibody comprises a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SYAMS (SEQ ID NO: 1); a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of AISGSGGSTYYADSVKG (SEQ ID NO: 2); and a variable heavy chain complementarity determining region 3 (VH CDR3) comprising the amino acid sequence of DGSSGWYVPHWFDP (SEQ ID NO: 3); a variable light chain complementarity determining region 1 (VL CDR1) comprising the amino acid sequence of TRSSGSIASNYVQ (SEQ ID NO: 4); a variable light chain complementarity determining region 2 (VL CDR2) region comprising the amino acid sequence of EDNQRPS (SEQ ID NO: 5); and a variable light chain complementarity determining region 3 (VL CDR3) region comprising the amino acid sequence of QSYDGSNRWM (SEQ ID NO: 6), wherein the concentration of antibody is at 5 mg/ml, and wherein the pH of the solution is between 5.8 and 6.2.
6. The unit dose vial of claim 5 , wherein the antibody is solubilized in the solution such that the solution is clear, colorless, and without precipitate.
7. The unit dose vial of claim 5 , wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO. 47, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48.
8. A method of treating a condition in a human subject by administering the unit dose vial of claim 5 , wherein the condition is primary hemophagocytic lymphohistiocytosis (HLH) or secondary HLH.
9. The method of claim 8 , wherein the human subject is pediatric or adult.