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Liquid composition comprising antibody of human interleukin-4 receptor alpha

A technology of liquid composition and human interleukin, which is applied in the direction of antibodies, drug combinations, antibody medical components, etc., can solve the problems of not being able to pass through the filter membrane, increase the side effects of drugs, and large deviations in dosage, so as to achieve easy production and storage, and improve Effect of drug efficacy, good thermal stability

Active Publication Date: 2020-09-22
SUZHOU CONNECT BIOPHARMACEUTICALS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the best way to administer this type of antibody drug is subcutaneous injection, and the dose required to exert its effect is relatively high, so it is often necessary to prepare high-concentration preparations
However, high concentration antibody preparations are often accompanied by many difficulties
For example, the viscosity of this type of preparation is very high, it is very difficult to suck and push the drug when using the syringe, the high residue of the drug in the container and the syringe causes large deviations in the administered dose, and causes pain at the injection site, etc.; in addition, the preparation The high viscosity will also bring serious technical problems in its production process, such as the concentration and filtration process requires extremely high pressure, or it cannot pass through the filter membrane at all
For another example, the high concentration of antibody protein in the preparation is very easy to aggregate, causing the preparation to be unstable, easy to form insoluble particles, increase the immunogenicity of the drug, and increase the side effects of the drug, etc.

Method used

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  • Liquid composition comprising antibody of human interleukin-4 receptor alpha
  • Liquid composition comprising antibody of human interleukin-4 receptor alpha
  • Liquid composition comprising antibody of human interleukin-4 receptor alpha

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] Example 1 pH value and buffer

[0106] The pH range and buffers of CBP-201 formulations were studied. Choose pH 5.4, 5.6, 5.8, 6.0, 6.2, 6.4, a total of 6 points, choose sodium acetate, histidine hydrochloride, sodium dihydrogen phosphate as buffer, and add sodium chloride. The following protein solutions containing 133.6mg / ml CBP-201 were subjected to accelerated experiments at 40°C to determine the appropriate pH range and buffer (see Table 1).

[0107] Table 1 pH value and buffer

[0108] serial number protein solution pH Preparation volume A 10mM NaAc 150mM NaCl 5.4 1L B 10mM NaAc 150mM NaCl 5.6 1L C 10mM His-HCl 150mM NaCl 5.8 3L D 10mM His-HCl 150mM NaCl 6.5 1L E 10mM NaH2PO4 150mM NaCl 6.4 1L

[0109] Appearance, protein concentration, SEC purity, CE-SDS purity, charge heterogeneity, DSC, and viscosity items were detected through accelerated experiments at 40°C.

[0110] Appearance inspection results...

Embodiment 2

[0120] Example 2 Protective agent

[0121] Suitable protectants for CBP-201 formulations were investigated. At pH 6.0, trehalose, sucrose, mannitol, proline, arginine hydrochloride, glycine, and sodium chloride were added, and the sodium chloride group was used as a control. The following protein solutions containing 133.6 mg / ml CBP-201 were subjected to accelerated experiments at 40°C to determine suitable protective agents (see Table 2).

[0122] Table 2 Protective agent

[0123]

[0124] Through accelerated experiments at 40°C, the appearance, protein concentration, SEC purity, CE-SDS purity, charge heterogeneity, viscosity, and DSC items were detected.

[0125] Appearance inspection results: all protein solutions were whitish in appearance.

[0126] Protein concentration test results: the protein concentrations were all within the range of 133.6±5% mg / ml.

[0127] In addition, after accelerating 2W at 40°C for protein solutions under different protective agent con...

Embodiment 3

[0134] Example 3 Viscosity in buffer only

[0135] Investigate the change of viscosity with concentration of CBP-201 in the case of only buffer (pH6.0 10mmol / L His-HCl) without protective agent, so as to judge the effect of each protective agent on reducing the viscosity of the preparation; challenge the highest concentrated concentration , and detect the viscosity to provide a basis for the selection of protein concentration in the preparation. The buffer solution in this embodiment does not contain NaCl, which is compared with the previous experiment containing NaCl.

[0136] Dialyze the protein with dialysis buffer (pH6.0 10mmol / L His-HCl), and concentrate the dialyzed protein to 71.23mg / ml, 89.04mg / ml, 106.85mg / ml, 133.56mg / ml, >151.37mg / ml (Protein concentration detection), and then filtered. Carry out appearance and viscosity inspection. The experimental results are shown in Table 3. Figure 18 .

[0137] Table 3 The protein solution appearance and viscosity test ...

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Abstract

The invention discloses a liquid composition comprising an antibody of human interleukin-4 receptor alpha. The liquid composition comprises the antibody at a concentration of 50-200 mg / ml, a buffer agent, a protective agent and a surfactant, wherein the buffer agent, the protective agent and the surfactant serve as auxiliary materials, and the liquid composition has pH of 5.4 to 6.4. When the pharmaceutical composition is used for subcutaneous injection or intravenous injection, the high-dose antibody can be provided, the administration requirement is met, and the curative effect of a medicineis improved.

Description

technical field [0001] The invention relates to the field of biopharmaceutical preparations, in particular, the invention relates to a stable liquid preparation containing high-concentration antibodies. Background technique [0002] The human interleukin-4 receptor is known to produce a soluble form of the protein (shIL-4Rα) that inhibits IL-4-mediated cell proliferation and T cell-mediated IL-5 raised. Both forms of this receptor are associated with allergic reactions, which manifest in conditions such as allergic rhinitis, sinusitis, asthma or eczema. Therefore, blocking antibodies targeting this protein are helpful for treating and alleviating such diseases. [0003] At present, monoclonal antibody drugs targeting hIL-4R have entered clinical trials, such as Dupilumab, which has shown good efficacy in phase II clinical trials for the treatment of atopic dermatitis. However, the best way to administer this type of antibody drug is subcutaneous injection, and the dose re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K9/08A61K47/02A61K47/12A61K47/18A61P17/00A61P37/08A61P11/02A61P19/02A61P37/02A61P1/00A61P11/06A61P29/00
CPCA61K39/3955A61K9/08A61K47/183A61K47/12A61K47/02A61P17/00A61P37/08A61P11/02A61P19/02A61P37/02A61P1/00A61P11/06A61P29/00C07K16/2866C07K2317/94A61K9/0019A61K47/26A61K39/39591A61K47/22A61P1/04C07K16/28A61K2039/505A61K47/10
Inventor 郑伟潘武宾杨欣陈阳张立民蒋洁
Owner SUZHOU CONNECT BIOPHARMACEUTICALS LTD
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