Stable anti-pd-1 antibody pharmaceutical preparation and application thereof in medicine

Abstract

A stable anti-PD-1 antibody pharmaceutical preparation and an application thereof in a medicine. The anti-PD-1 antibody pharmaceutical preparation comprises an anti-PD-1 antibody, a buffer, and can further comprise at least one type of stabilizer, and optionally can further con a surfactant. The anti-PD-1 antibody pharmaceutical preparation of the present invention can effectively suppress antibody aggregation and deamidation, thereby preventing degradation of an antibody product, obtaining a stable injected pharmaceutical preparation.

It is claimed: 
     
         1 . An anti-PD-1 antibody comprising a heavy chain having the amino acid sequence of SEQ ID NO: 7 and alight chain having the amino acid sequence of SEQ ID NO: 8. 
     
     
         2 . A pharmaceutical composition comprising the anti-PD-1 antibody of  claim 1 . 
     
     
         3 . The pharmaceutical composition of  claim 2 , being an injectable pharmaceutical formulation further comprising water for injection. 
     
     
         4 . A lyophilized powder prepared from the pharmaceutical formulation of  claim 2 . 
     
     
         5 . A method of blocking the binding of PD-1 to PD-L1 in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 2 . 
     
     
         6 . The method of  claim 5 , wherein the subject is in need of a treatment of a cancer selected from the group consisting of breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer, and melanoma. 
     
     
         7 . The method of  claim 5 , wherein the pharmaceutical composition is an injectable pharmaceutical formulation further comprising water for injection. 
     
     
         8 . A method of blocking the binding of PD-1 to PD-L1 in a subject in need thereof, comprising administering to the subject a stable pharmaceutical formulation comprising:
 (i) an anti-PD-1 antibody comprising a heavy chain having the amino acid sequence of SEQ ID NO: 7 and a light chain having the amino acid sequence of SEQ ID NO: 8;   (ii) a buffer selected from the group consisting of an acetate buffer, a citrate buffer, a succinate buffer, and a phosphate buffer;   (iii) a stabilizer selected from the group consisting of a saccharide and an amino acid, and   (iv) a surfactant selected from the group consisting of polyoxyethylene hydrogenated castor oil, a glycerol fatty acid ester, and a polyoxyethylene sorbitan fatty acid ester.   
     
     
         9 . The method of  claim 8 , wherein the concentration of the anti-PD-1 antibody in the pharmaceutical formulation is in the range of 1 mg/ml to 60 mg/ml. 
     
     
         10 . The method of  claim 8 , wherein the buffer is the acetate buffer. 
     
     
         11 . The method of  claim 10 , wherein the concentration of the buffer is 1 mM to 50 mM. 
     
     
         12 . The method of  claim 8 , wherein the pH of the formulation ranges from 4.5 to 6.0. 
     
     
         13 . The method of  claim 8 , wherein the at least one stabilizer comprises a disaccharide selected from the group consisting of sucrose, lactose, trehalose, and maltose. 
     
     
         14 . The method of  claim 13 , wherein the disaccharide is at concentration from 30 mg/ml to 120 mg/ml. 
     
     
         15 . The method of  claim 8 , wherein the surfactant is the polyoxyethylene sorbitan fatty acid ester selected from the group consisting of polysorbate 20, 40, 60 and 80. 
     
     
         16 . The method of  claim 15 , wherein the surfactant is at a concentration from 0.01 mg/ml to 1 mg/ml. 
     
     
         17 . The method of  claim 8 , wherein the pharmaceutical formulation is an injectable pharmaceutical formulation winch further comprises water for injection. 
     
     
         18 . The method of  claim 8 , wherein the subject is in need of a treatment of a cancer selected from the group consisting of breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer, and melanoma. 
     
     
         19 . A method of treating a cancer selected from the group consisting of breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer, and melanoma in a subject in need thereof, comprising administering to the subject a pharmaceutical formulation comprising:
 (a) an anti-PD-1 antibody, wherein the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 7, and a light chain having the amino acid sequence of SEQ ID: 8; and   (b) at least one of:
 (i) 90 mg/ml α,α-trehalose dihydrate, and 10 mM acetate buffer at pH 5.2; 
 or 
 (ii) 90 mg/ml α,α-trehalose dihydrate, 0.2 mg/ml polysorbate 20, and 10 mM acetate buffer at pH 5.2; or 
 (iii) 90 mg/ml α,αtrehalose dihydrate, 0.2 mg/ml polysorbate 20, and 20 mM acetate buffer at pH 5.4; or 
 (iv) 60 mg/ml α,α-trehalose dihydrate, 0.4 mg/ml polysorbate 20, and 20 mM acetate buffer at pH 5.0; or 
 (v) 60 mg/ml α,α-trehalose dihydrate, 0.1 mg/ml polysorbate 20, and 20 mM acetate buffer at pH 5.2; or 
 (vi) 60 mg/ml α,α-trehalose dihydrate, 0.2 mg/ml polysorbate 20, and 10 mM acetate buffer at pH 5.2; or 
 (vii) 30 mg/ml α,α-trehalose dihydrate, 0.4 mg/ml polysorbate 20, and 10 mM acetate buffer at pH 4.8; or 
 (viii) 30 mg/ml α,α-trehalose dihydrate, 0.2 mg/ml polysorbate 20, and 30 mM acetate buffer at pH 5.2; or 
 (ix) 30 mg/ml α,α-trehalose dihydrate, 0.4 mg/ml polysorbate 20. and 10 mM acetate buffer at pH 5.6; or 
 (x) 90 mg/ml α,α-trehalose dihydrate, 0.2 mg/ml polysorbate 20, 10 mM acetate buffer, and the pH of the formulation is 5.2, wherein the concentration of the anti-PD-1 antibody in (x) is 40 mg/ml. 
   
     
     
         20 . The method of  claim 19 , wherein the pharmaceutical formulation is an injectable pharmaceutical formulation which further comprises water for injection.