Liquid preparation of recombinant anti-PD-L1 whole-human monoclonal antibody

A monoclonal antibody, liquid preparation technology, applied in the direction of antibodies, anti-tumor drugs, drug combinations, etc., can solve the problem of difficulty in obtaining liquid preparations, and achieve the effect of good stability

Inactive Publication Date: 2017-09-26
CSTONE PHARM (SUZHOU) CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, proteins are prone to form aggregates and particles in solution, which has always been a problem in the development of protein products for parenteral administration
Especially for the PD-L1 fully human monoclonal antibody in the patent publication number CN106432501A, experiments have found that it is very easy to form agglomerates in a solution state, and it is difficult to obtain a stable liquid preparation

Method used

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  • Liquid preparation of recombinant anti-PD-L1 whole-human monoclonal antibody
  • Liquid preparation of recombinant anti-PD-L1 whole-human monoclonal antibody
  • Liquid preparation of recombinant anti-PD-L1 whole-human monoclonal antibody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The screening of embodiment 1 buffer system kind

[0048] The formula of the recombinant anti-PD-L1 fully human monoclonal antibody liquid preparation of this embodiment is as follows:

[0049] Formula 1: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM acetic acid / sodium acetate buffer system, pH value is 4.5;

[0050] Formula 2: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM acetic acid / sodium acetate buffer system, pH value is 5.0;

[0051] Formula 3: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM citric acid / sodium citrate buffer system, pH 5.0;

[0052] Formula 4: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM citric acid / sodium citrate buffer system, pH value is 5.5;

[0053] Formula 5: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM citric acid / sodium citrate buffer system, pH value is 6.0;

[0054] Formula 6: 30mg / ml recombinant anti-PD-L1 fully hum...

Embodiment 2

[0063] Embodiment 2 auxiliary material screening test

[0064] The formula of the recombinant anti-PD-L1 fully human monoclonal antibody liquid preparation of this embodiment is as follows:

[0065] Formula 9: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM histidine-histidine hydrochloride buffer + 150mM trehalose + 55mM sodium chloride + 0.01wt% polysorbate 80;

[0066] Formula 10: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM histidine-histidine hydrochloride buffer + 150mM sucrose + 55mM sodium chloride + 0.03wt% polysorbate 80;

[0067] Formula 11: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM histidine-histidine hydrochloride buffer + 150mM glycine + 55mM sodium chloride + 0.05wt% polysorbate 80;

[0068] Formula 12: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM histidine-histidine hydrochloride buffer + 150mM mannitol + 55mM sodium chloride + 0.05wt% polysorbate 80;

[0069] ...

Embodiment 3

[0075] The screening test of embodiment 3 surfactants

[0076] Formula 13: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM histidine-histidine hydrochloride buffer + 150mM mannitol + 55mM sodium chloride + 0.01wt% polysorbate 80;

[0077] Formula 14: 30mg / ml recombinant anti-PD-L1 fully human monoclonal antibody + 20mM citrate buffer + 150mM mannitol + 55mM sodium chloride + 0.05wt% polysorbate 80;

[0078] The preparation method of the recombinant anti-PD-L1 fully human monoclonal antibody liquid preparation of the above formulations is the same as that in Example 1.

[0079]The samples of the above formulations 13 and 14 were sampled and divided into two groups, which were respectively placed under the conditions of 40°C 75% RH and 25°C 100rpm shaking conditions for investigation. The samples were taken at 2 weeks and 4 weeks for purity testing, and cation exchange chromatography CEX -HPLC detects, and the investigation results are shown in Table 3:

...

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Abstract

The invention discloses a stable liquid preparation of a recombinant anti-PD-L1 whole-human monoclonal antibody. The liquid preparation is prepared from a recombinant anti-PD-L1 whole-human monoclonal antibody, a buffer solution, a stabilizing agent, an osmotic pressure regulator and a surfactant, wherein the buffer solution is a histidine-histidine hydrochloride buffer solution; the stabilizing agent is mannitol; the osmotic pressure regulator is sodium chloride; the surfactant is polysorbate 80. The liquid preparation of the recombinant anti-PD-L1 whole-human monoclonal antibody has superior stability, and can be stored stably at the temperature of 5+ / -3 DEG C for at least 24 months.

Description

technical field [0001] The invention relates to the field of biological preparations, in particular to a liquid preparation of a stable recombinant anti-PD-L1 fully human monoclonal antibody. Background technique [0002] The full name of PD-1 is programmed death receptor 1, and its English name is programmed death 1. It is an important immunosuppressive molecule and a member of the CD28 family. The full name of PD-L1 is programmed death receptor-ligand 1, and its English name is programmed cell death-Ligand 1. It is the first type of transmembrane protein with a size of 40kDa. Immune regulation targeting PD-L1 is of great significance in anti-tumor, anti-infection, anti-autoimmune diseases, and organ transplant survival. [0003] Under normal circumstances, the immune system will respond to foreign antigens accumulated in the lymph nodes or spleen, promoting the proliferation of antigen-specific T cells. The combination of programmed cell death receptor-1 (PD-1) and progr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00A61P31/00A61P37/02A61P37/06
CPCC07K16/2827C07K2317/56C07K2317/565C07K2317/94
Inventor 吴晓丽刘琴贾春媛王叶飞罗建军周伟昌陈智胜
Owner CSTONE PHARM (SUZHOU) CO LTD
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