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US 11,628,217 B2Granted
Highly concentrated low viscosity MASP-2 inhibitory antibody formulations, kits, and methods
AssigneeOmeros Corporation
InventorsGregory A. Demopulos, Kenneth M. Ferguson, William Joseph Lambert, John Steven Whitaker
Life of this patent
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Abstract
The present invention relates to stable, high-concentration low-viscosity formulations of MASP-2 inhibitory antibodies, kits comprising the formulations and therapeutic methods using the formulations and kits for inhibiting the adverse effects of MASP-2 dependent complement activation.
Claims28
A stable aqueous pharmaceutical formulation suitable for subcutaneous administration to a mammalian subject, consisting of:
- (a) a sodium citrate or histidine buffer system having a pH of 5.5 to 6.5, wherein the sodium citrate or histidine is at a concentration of from 10 mM to 50 mM;
- (b) a monoclonal antibody that specifically binds to human Mannan-binding lectin-associated serine protease-2 (MASP-2) at a concentration of from 150 mg/mL to 200 mg/mL, wherein said antibody is a human IgG4 antibody comprising (i) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:2, and (ii) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:3;
- (c) arginine at a concentration of from 200 mM to 300 mM, wherein the arginine is present in a sufficient amount for the formulation to be hypertonic;
- and
- (d) polysorbate 80 (PS-80) at a concentration from 0.001% (w/v) to 0.1% (w/v);
- wherein the formulation has a viscosity suitable for subcutaneous administration of between 2 and 25 centipoise (cP) as measured at about 25° C. with a shear rate in the range of 100,000 to 250,000 l/sec, and wherein the formulation has at least 95% monomeric antibody as determined by size exclusion chromatography (SEC) after storage at between 2° C. and 8° C. for at least six months.
3 more elements
A stable aqueous pharmaceutical formulation suitable for parenteral administration to a mammalian subject, the formulation consisting of:
- (a) polysorbate 80 at a concentration from 0.01 to 0.08% w/v;
- (b) L-arginine HCl at a concentration of 200 mM;
- (c) sodium citrate at a concentration of 20 mM;
- and
- (d) a monoclonal antibody that specifically binds to human Mannan-binding lectin-associated serine protease-2 (MASP-2) at a concentration of from 175 mg/mL to 195 mg/mL, wherein said antibody is a human IgG4 isotype antibody comprising (i) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:2, and (ii) a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:3;
- wherein the formulation has a pH from about 5.5 to about 6.5, a viscosity of between 2 and 25 centipoise (cP) as measured at about 25° C. with a shear rate in the range of 100,000 to 250,000 l/sec, and wherein the formulation has at least 95% monomeric antibody as determined by size exclusion chromatography (SEC) after storage at between 2° C. and 8° C. for at least six months.
3 more elements
Dependencies are inferred from the claim text.