PHARMACEUTICAL COMPOSITIONS OF HER2 ANTIBODY CONJUGATE Russian patent published in 2023 - IPC A61K9/19 A61K47/10 A61K47/18 A61K47/26 A61K47/64 A61K47/68 A61P35/00 

FIELD: medicine.

SUBSTANCE: group of inventions relates to an aqueous liquid pharmaceutical composition of an antibody-drug conjugate for the treatment of a disease caused by a violation of HER2 expression, where the composition includes an antibody-drug conjugate, a non-reducing sugar, an amino acid and a solubilizer, the antibody-drug conjugate is an anti-HER2-vc-MMAE monoclonal antibody, wherein the anti-HER2 monoclonal antibody is linked to MMAE via a vc linker, and the structure of the linker and MMAE after linkage is as follows:

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the antibody in the antibody-drug conjugate comprises a heavy chain and a light chain, wherein the heavy chain contains CDRs 1-3 having the amino acid sequences as shown in SEQ ID NO: 1, 2 and 3, respectively, and wherein the light chain contains CDRs 1-3 having the amino acid sequences as shown in SEQ ID NO: 4, 5 and 6, respectively; the concentration of monoclonal antibodies against HER2-vc-MMAE is 5–30 mg/ml; non-reducing sugar is 240–260 mmol/l mannitol and 40–60 mmol/l sucrose, the amino acid is 8–12 mmol/l histidine hydrochloride, and the solubilizer is 0–0.02 w/v.% Tween 80; the aqueous liquid pharmaceutical composition has a pH of 5.6–6.8, also refers to a lyophilized pharmaceutical composition of an antibody-drug conjugate for the treatment of a disease caused by a disorder in the expression of HER2, and also refers to the use of a pharmaceutical composition in the manufacture of a medicament for the treatment of a disease caused by disruption of HER2 expression.

EFFECT: group of inventions provides for obtaining a conjugate of a monoclonal antibody against Her2 with MMAE, which can dissolve well before and after lyophilization, while insoluble microparticles, as well as a visible precipitate, meet the standards for human injection; in addition, the conjugate can remain stable for a long time during lyophilization and storage, can resist to polymerization or decomposition after reconstitution, and still maintain good biological activity.

12 cl, 2 dwg, 16 tbl, 7 ex