Excipients To Reduce the Viscosity of Antibody Formulations and Formulation Compositions
AssigneeAmgen Inc.
InventorsJian Hua GU, Robert M. FESINMEYER, Rulin QIAN
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Abstract
This invention concerns a series of excipients capable of effectively reducing the viscosity of protein formulations. The viscosity reducing excipients are oligopeptides (e.g., dipeptides, tripeptides) comprising at least one arginine. The peptides may also include basic or acidic or hydrophilic or hydrophobic/aromatic amino acids. An arginine residue may be either at the amino or the carboxyl end of the oligopeptide.
Claims20
A liquid pharmaceutical formulation comprising an antibody, a buffer, and at least one oligopeptide, wherein (i) the oligopeptide comprises an arginine residue and consists of 2 to 10 amino acid residues but is not arg-asp, arg-glu, or poly-arginine, (ii) the buffer is acetate, glutamate, or phosphate and (iii) the pH of the formulation is about 4.5 to about 6.5.
The formulation of claim 8, wherein the second oligopeptide is selected from Arg-Lys, Arg-Pro, Arg-Ala, Asp-Arg, Lys-Arg, Pro-Arg, Val-Arg, Ala-Arg, Phe-Arg, and Arg-Tyr and the one or more amino acids are selected from arginine, proline, n-acetyl arginine, n-acetyl lysine, n-acetyl histidine, n-acetyl proline.
A method of reducing viscosity in a pharmaceutical formulation comprising an antibody, wherein the method comprises:
- providing a solution at a pH of about 4.5 to about 6.5 comprising (i) the antibody, (ii) an oligopeptide salt, wherein the oligopeptide comprises an arginine residue, consists of 2 to 10 amino acid residues and is present in a viscosity-reducing concentration, and (iii) a buffer.
A pharmaceutical formulation of tezepelumab, which comprises an excipient selected from arginine, proline, proline and arginine, N-acetyl arginine, Arg-Lys, Arg-Phe, Arg-Pro, Arg-Val, Arg-Ala, Asp-Arg, Lys-Arg, Pro-Arg, Leu-Arg, Val-Arg, or Ala-Arg.
A pharmaceutical formulation of PCSK9 binding polypeptide, wherein the formulation comprises an excipient selected from Arg-Phe, Arg-Ala, Arg-Val, Pro-Arg, Val-Arg, Ala-Arg, Phe-Arg, Arg-Tyr, and Arg-Phe.
Dependencies are inferred from the claim text.