Stable compositions of high-concentration allotype-selected antibodies for small-volume administration

摘要

Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

主权项

1. A composition for subcutaneous administration comprising an antibody in high concentration formulation buffer, wherein the antibody or immunoglobulin is concentrated to at least 300 mg/ml, wherein the buffer is pH 5.2 and comprises 6.2 mM citric acid monohydrate, 105 mM sodium chloride, 1.2 mM sodium citrate dihydrate, 8.7 mM sodium phosphate dibasic, 5.5 mM sodium phosphate monobasic, 0.1% polysorbate 80 and 66 mM mannitol, wherein the antibody is a chimeric, humanized or human antibody of nG1m1 allotype, wherein the nG1m1 allotype is characterized by glutamate at Kabat residue 356 and methionine at Kabat residue 358 of the antibody heavy chain.