High concentration formulations of anti-CSF1 and anti-CSF1R antibodies
Inventors
Alani, Laman • Hsu, Chung-Chiang • Zhu, Aihua • Johnson, Kirk William • Huang, Michael
Assignees
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Publication Number
US-12178915-B2
Publication Date
2024-12-31
Expiration Date
Abstract
Provided are high concentration stable formulations of anti-CSF1R/CSF1 antibodies. An example formulation includes 105 to 250 mg/mL of the antibody, 100 mM to 200 mM of arginine glutamate or arginine HCl, 10 mM to 50 mM histidine, and 0.015 to 0.035 w/v % of polysorbate 80, at a pH of 5.4 to 5.6. Also provided are methods of using the formulations for treating diseases.
Core Innovation
The invention relates to high-concentration, pH-buffered aqueous and lyophilized formulations of anti-CSF1/anti-CSF1R antibodies. The aqueous pharmaceutical composition includes an antibody at at least 105 mg/mL, formulated at a pH of 5.0-6.0, and the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:7 and a light chain comprising the amino acid sequence of SEQ ID NO:8.
The formulation further includes a salt of arginine selected from arginine glutamate, arginine aspartate, and arginine HCl, together with histidine and polysorbate selected from PS 80 and PS 20. The disclosed formulation defines selected excipients in an acidic pH window and provides experimental findings that stable high viscosity and low aggregation are achieved in a narrow acidic pH window using histidine plus an arginine salt.
The document contrasts the claimed excipient choices with alternative excipients that can increase opalescence/turbidity, viscosity, aggregation, or phase separation, including NaCl, citrate, many sugars/polyols, succinate/proline/sorbitol, and lysine. The invention also includes lyophilized compositions that reconstitute with water to form the disclosed aqueous pharmaceutical formulation.
Claims Coverage
The independent claims cover a high-concentration antibody formulation with specified SEQ ID sequences, a constrained acidic pH, and a defined combination of arginine salt, histidine, and polysorbate (PS80 or PS20), with a lyophilized format that reconstitutes to the aqueous formulation. The main inventive features are extracted for the independent claim coverage described in the input.
High-concentration antibody formulation with specified SEQ ID sequences
An aqueous pharmaceutical composition comprising at least 105 mg/mL of an antibody, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:7 and a light chain comprising the amino acid sequence of SEQ ID NO:8.
Arginine salt plus histidine at acidic pH
An aqueous pharmaceutical composition comprising a salt of arginine selected from arginine glutamate, arginine aspartate, and arginine HCl, and histidine, at a pH of 5.0-6.0.
Polysorbate selection in the formulation
An aqueous pharmaceutical composition further comprising polysorbate selected from PS 80 and PS 20.
Lyophilized solid that reconstitutes to the aqueous composition
A lyophilized solid composition made from the aqueous pharmaceutical composition of the claim, which can also be reconstituted to form that same aqueous pharmaceutical composition by mixing with water.
Overall, the claim coverage centers on a high-concentration antibody formulation with SEQ ID NO:7 and SEQ ID NO:8, formulated at pH 5.0-6.0 with an arginine salt, histidine, and polysorbate (PS80 or PS20), and includes a lyophilized format that reconstitutes to the aqueous pharmaceutical composition.
Stated Advantages
Stable high viscosity and low aggregation are achieved in a narrow acidic pH window with selected excipients.
Certain alternative excipients are avoided to reduce increased opalescence/turbidity, increased viscosity, increased aggregation, or phase separation.
Documented Applications
Treating TGCT/PVNS, including local/subcutaneous administration.
Treating idiopathic pulmonary fibrosis (IPF).
Treating polycystic kidney disease (PKD).
Treating ocular diseases.
Lyophilized compositions that reconstitute to the aqueous formulation.
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