Highly concentrated low viscosity MASP-2 inhibitory antibody formulations, kits, and methods
Inventors
Demopulos, Gregory A. • Ferguson, Kenneth M. • Lambert, William Joseph • Whitaker, John Steven
Assignees
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Publication Number
US-11628217-B2
Publication Date
2023-04-18
Expiration Date
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.
Core Innovation
The disclosed innovation is a stable, high-concentration, low-viscosity aqueous pharmaceutical formulation containing a human IgG4 monoclonal antibody, such as OMS646, that specifically binds human MASP-2. The formulation combines a citrate or histidine buffer system, arginine or L-arginine HCl, and polysorbate 80 for parenteral administration, particularly subcutaneous administration.
The formulations demonstrate syringeability, low viscosity, and refrigerated storage stability with retention of monomeric antibody and MASP-2-binding functionality. The compositions are associated with prefilled delivery devices and kits, and show selective inhibition of lectin-pathway MAC deposition without inhibiting classical or alternative complement pathways.
Claims Coverage
The claim coverage comprises two inventive features directed to stable aqueous formulations of a MASP-2-binding human IgG4 monoclonal antibody.
Stable subcutaneous MASP-2 antibody formulation
The first independent claim covers a stable aqueous formulation suitable for subcutaneous administration, comprising a citrate or histidine buffer system, a MASP-2-binding human IgG4 monoclonal antibody, arginine, and polysorbate 80. Specific claim elements define viscosity parameters and retention of monomeric antibody during refrigerated storage.
Stable parenteral MASP-2 antibody formulation
The second independent claim covers a stable aqueous formulation suitable for parenteral administration, comprising sodium citrate, L-arginine HCl, polysorbate 80, and a MASP-2-binding human IgG4 monoclonal antibody. Specific claim elements define pH, viscosity parameters, and retention of monomeric antibody during refrigerated storage.
Together, the independent claims cover stable aqueous formulations containing a MASP-2-binding human IgG4 monoclonal antibody tailored for subcutaneous or parenteral administration with defined excipients, viscosity, and storage stability parameters.
Stated Advantages
Polysorbate 80 reduces viscosity and improves syringeability, including through small-gauge needles.
Citrate and histidine formulations maintain refrigerated storage stability, retaining at least 95% monomeric antibody after extended storage while preserving MASP-2-binding functionality.
Selective inhibition of lectin-pathway MAC deposition is achieved without inhibition of the classical or alternative complement pathways.
Documented Applications
Parenteral administration, particularly subcutaneous administration, of the MASP-2 antibody formulation to a mammalian subject.
Prefilled delivery devices and kits configured for administration of the formulation.
Therapeutic use in treating MASP-2-dependent complement disorders.
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