Anti-PD-1 monoclonal antibody liquid preparation

Abstract

The invention provides an anti-PD-1 monoclonal antibody liquid preparation. The anti-PD-1 monoclonal antibody liquid preparation comprises an anti-PD-1 monoclonal antibody, a buffer solution, a protein protective agent and a surfactant. The liquid preparation can be used for protecting the anti-PD-1 monoclonal antibody and improving the stability of an IgG4 type anti-PD-1 monoclonal antibody. The liquid preparation can be preserved at 2-8 DEG C for at least 60 months and at 25 DEG C for at least 6 months, and is suitable for being used as an injection to be clinically applied.

Description

technical field

[0001] The present invention relates to the field of antibody pharmaceutical preparations, in particular to a liquid anti-PD-1 monoclonal antibody preparation. Background technique

[0002] Programmed death receptor 1 (PD-1) is an important immunosuppressive molecule, and its ligand is programmed death receptor-ligand 1 (PD-L1). 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. One way for tumor cells to escape the destruction of T cells as an antigen is to produce PD-L1 on its surface. When PD-1 on the surface of immune cells T cells recognizes PD-L1, it can transmit inhibitory signals, and T cells cannot find tumor cells and send an attack signal to tumor cells. The mechanism of action of PD-1 immunotherapy is to design specific protein antibodies against PD-1, prevent the recognition process of PD-1 and PD-L1, and partially rest...

Examples

Embodiment 1

[0048] The influence of embodiment 1pH on formula

[0049] Prepare 5 kinds of buffer solutions with different pH values ​​in Table 1, and prepare the protein and auxiliary materials to obtain the prescription solutions in the following table. After being sterilized and filtered by a 0.22μm filter membrane, 1ml / bottle was divided into 2ml vials, stoppered and capped to obtain candidate prescription samples, and placed in a stability test box at 40±2°C. Sampling and investigation at 2 weeks, 4 weeks, 6 weeks, and 8 weeks, and the inspection indicators are SEC purity and IEC purity.

[0050] Table 1 pH investigation

[0051]

[0052] The results are shown in Table 2. The results show that with the increase of the pH value, the decrease rate of the SEC purity of the protein in each prescription solution is gradually accelerated, and the pH range of 4.5-6.0 is better. The change trend of IEC purity shows that prescription 1-2, prescription 1-3 and prescription 1-4 are better t...

Embodiment 2

[0055] The impact of embodiment 2 buffer system on formula

[0056] Prepare 4 different buffer system solutions in Table 3, and prepare the protein and excipients to obtain the target prescription solution. After being sterilized and filtered by a 0.22μm filter membrane, 1ml / bottle was divided into 2ml vials, stoppered and capped to obtain candidate prescription samples, and placed in a stability test box at 40±2°C. Sampling and investigation at 2 weeks, 4 weeks, 6 weeks, and 8 weeks, and the inspection indicators are SEC purity and IEC purity.

[0057] Table 3 Buffer system screening prescription information

[0058]

[0059] Investigating the stability of each formulation under the condition of 40±2℃, the change trend of SEC purity and IEC purity showed that prescription 2-1 and prescription 2-2 were better than prescription 2-3 and prescription 2-4; There were no significant differences between prescriptions. It can be seen that the acetic acid buffer system and the h...

Embodiment 3

[0063] Embodiment 3 albumen protectant and surfactant affect formula

[0064] Prepare the histidine-histidine hydrochloride buffer system in Table 5, and prepare the protein and excipients to obtain the target prescription solution. After being sterilized and filtered by a 0.22μm filter membrane, 1ml / bottle was divided into 2ml vials, stoppered and capped to obtain candidate prescription samples, and placed in a stability test box at 40±2°C. Sampling and investigation at 2 weeks, 4 weeks, and 8 weeks, and the inspection indicators are SEC purity, IEC purity, and insoluble particles.

[0065] Table 5 Screening Prescription Information of Protein Protectants and Surfactants

[0066]

[0067] The stability, insoluble particles and SEC purity of each formulation were investigated under the condition of 40±2°C. The results further showed that the addition of sugar protective agent and polysorbate in the formulation could effectively improve the stability; there was no significa...

technical field

[0001] The present invention relates to the field of antibody pharmaceutical preparations, in particular to a liquid anti-PD-1 monoclonal antibody preparation. Background technique

[0002] Programmed death receptor 1 (PD-1) is an important immunosuppressive molecule, and its ligand is programmed death receptor-ligand 1 (PD-L1). 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. One way for tumor cells to escape the destruction of T cells as an antigen is to produce PD-L1 on its surface. When PD-1 on the surface of immune cells T cells recognizes PD-L1, it can transmit inhibitory signals, and T cells cannot find tumor cells and send an attack signal to tumor cells. The mechanism of action of PD-1 immunotherapy is to design specific protein antibodies against PD-1, prevent the recognition process of PD-1 and PD-L1, and partially rest...

Examples

Embodiment 1

[0048] The influence of embodiment 1pH on formula

[0049] Prepare 5 kinds of buffer solutions with different pH values ​​in Table 1, and prepare the protein and auxiliary materials to obtain the prescription solutions in the following table. After being sterilized and filtered by a 0.22μm filter membrane, 1ml / bottle was divided into 2ml vials, stoppered and capped to obtain candidate prescription samples, and placed in a stability test box at 40±2°C. Sampling and investigation at 2 weeks, 4 weeks, 6 weeks, and 8 weeks, and the inspection indicators are SEC purity and IEC purity.

[0050] Table 1 pH investigation

[0051]

[0052] The results are shown in Table 2. The results show that with the increase of the pH value, the decrease rate of the SEC purity of the protein in each prescription solution is gradually accelerated, and the pH range of 4.5-6.0 is better. The change trend of IEC purity shows that prescription 1-2, prescription 1-3 and prescription 1-4 are better t...

Embodiment 2

[0055] The impact of embodiment 2 buffer system on formula

[0056] Prepare 4 different buffer system solutions in Table 3, and prepare the protein and excipients to obtain the target prescription solution. After being sterilized and filtered by a 0.22μm filter membrane, 1ml / bottle was divided into 2ml vials, stoppered and capped to obtain candidate prescription samples, and placed in a stability test box at 40±2°C. Sampling and investigation at 2 weeks, 4 weeks, 6 weeks, and 8 weeks, and the inspection indicators are SEC purity and IEC purity.

[0057] Table 3 Buffer system screening prescription information

[0058]

[0059] Investigating the stability of each formulation under the condition of 40±2℃, the change trend of SEC purity and IEC purity showed that prescription 2-1 and prescription 2-2 were better than prescription 2-3 and prescription 2-4; There were no significant differences between prescriptions. It can be seen that the acetic acid buffer system and the h...

Embodiment 3

[0063] Embodiment 3 albumen protectant and surfactant affect formula

[0064] Prepare the histidine-histidine hydrochloride buffer system in Table 5, and prepare the protein and excipients to obtain the target prescription solution. After being sterilized and filtered by a 0.22μm filter membrane, 1ml / bottle was divided into 2ml vials, stoppered and capped to obtain candidate prescription samples, and placed in a stability test box at 40±2°C. Sampling and investigation at 2 weeks, 4 weeks, and 8 weeks, and the inspection indicators are SEC purity, IEC purity, and insoluble particles.

[0065] Table 5 Screening Prescription Information of Protein Protectants and Surfactants

[0066]

[0067] The stability, insoluble particles and SEC purity of each formulation were investigated under the condition of 40±2°C. The results further showed that the addition of sugar protective agent and polysorbate in the formulation could effectively improve the stability; there was no significa...

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