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Cell programmed death acceptor 1 antibody preparation and use thereof

A formulation and pharmaceutical preparation technology, applied in the field of PD-1 antibody preparations, can solve the problems of different structures and properties, lack of protein preparations, etc.

Active Publication Date: 2020-02-14
SHANGHAI HENLIUS BIOTECH INC +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, antibody drugs have different structural properties and are easy to polymerize. At present, there is still a lack of stable protein preparations that meet the needs of the pharmaceutical industry.

Method used

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  • Cell programmed death acceptor 1 antibody preparation and use thereof
  • Cell programmed death acceptor 1 antibody preparation and use thereof
  • Cell programmed death acceptor 1 antibody preparation and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1. Sample Test Method

[0021] 1.1. Osmotic pressure detection

[0022] The pipette draws 20 μl of the sample and two osmotic pressure standards of 290 mOsmol / kg, and the Advanced 2020 osmometer is used to measure the osmotic pressure values ​​of the samples and the standard.

[0023] 1.2. SEC-HPLC

[0024] Agilent 1260 high performance liquid chromatography, TOSOH TSK G3000 (300*7.8 mm) chromatographic column was used to analyze the sample, the column temperature was room temperature, the flow rate was 0.5 mL / min, and the detection wavelength was 280 nm. The composition of the mobile phase was 100 mM PB, 0.5% NaCl, pH 6.8, the test sample was diluted to about 1.0 mg / mL with the mobile phase, 50 μL was injected, and the stop time was 30 min.

[0025] 1.3. CEX-HPLC

[0026] Agilent 1260 HPLC, Thermo ProPac WCX-10 column (4 × 250 mm) was used to analyze the sample, the column temperature was 35°C, the flow rate was 1.0 mL / min, the detection wavelength was 280 n...

Embodiment 2

[0031] Example 2. Preparation of Antibodies

[0032]The PD-1 antibody h1G4 is derived from the h1G4 disclosed in the patent application WO2018052818, and its preparation method fully refers to WO2018052818. The amino acid sequence of the PD-1 antibody h1G4 is as follows:

[0033] Table 2 CDR sequence of h1G4

[0034]

[0035] h1G4 antibody heavy chain variable region (VH) SEQ ID NO: 7

[0036] QVQLVESGGGLVKPGGSLRLSCAASG FTFS NYGMS WIRQAPGKGLEWVS TISGGGSNIY YADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYC VSYYYGIDF WGQGTSVTVSS

[0037] h1G4 antibody light chain variable region (VL) SEQ ID NO: 8

[0038] DIQMTQSPSSLSASVGDRVTITC KASQDVTTAVA WYQQKPGKAPKLLIY WASTRHT GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQHYTIPWT FGGGTKLEIK

[0039] h1G4 antibody light chain (LC) SEQ ID NO: 9

[0040] DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYWASTRHTGVPSRFSGSGSGTDFLTISSLQPEDFATYYCQQHYTIPWTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLGSKADYEVECKQGLSS ...

Embodiment 3

[0043] Embodiment 3. Buffer system screening research

[0044] In this study, two groups of different formulation buffer systems were selected as alternative formulations (hereinafter referred to as B1~B6), and the concentration of the target drug h1G4 antibody was 10.0 mg / mL. Among them, B1~B3 are 20 mmol / L citric acid-sodium citrate buffer system, the pH values ​​are 5.0, 5.5 and 6.0; B4~B6 are 20 mmol / L histidine-histidine hydrochloric acid buffer system, pH The values ​​are 5.0, 5.5 and 6.0; the above buffer systems all contain 3% mannitol, 0.02% polysorbate 80 and 0.3% sodium chloride as auxiliary materials, and the concentration percentages of auxiliary materials in this material refer to the mass volume ratio (w / v , g / L). See Table 3 for information on alternative prescriptions for screening research on the buffer system of h1G4 antibody preparations.

[0045] Table 3. Alternative buffer system compositions for h1G4 antibody preparations

[0046]

[0047] Take an ...

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PUM

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Abstract

The invention provides a pharmaceutical preparation containing a cell programmed death acceptor 1 monoclonal antibody. The pharmaceutical preparation comprises ingredients: a PD-1 monoclonal antibody,a citric acid-sodium citrate buffer solution, a protein protectant, a surfactant and an isotonicity regulator. According to the pharmaceutical preparation, proven by a longest-4-week accelerated experiment at a temperature of 40 DEG C, major detection indexes, i.e., testing equivalent standards such as appearance, concentration, turbidity (A350), pH value, osmotic pressure and purity are all freeof obvious changes, and good stability is shown.

Description

technical field [0001] The present invention relates to the field of biotechnology, in particular to a PD-1 antibody preparation and its application. Background technique [0002] Programmed death receptor 1 (programmed death 1, PD-1), also known as CD279, is an important immunosuppressive molecule, belonging to the CD28 family member of the immunoglobulin superfamily, and a type I transmembrane with a molecular weight of 50-55kD glycoprotein. PD-1 is persistently expressed on the surface of T cells, B cells, natural killer cells, monocytes and myeloid cells. PD-1 has two known ligands, PD-L1 and PD-L2. At present, studies have found that the combination of PD-1 and its ligand PD-L1 can transmit inhibitory signals and reduce the proliferation of lymph node CD8+ T cells, and PD-1 can also control the antigen in lymph nodes by regulating the Bcl-2 gene. Accumulation of specific T cells. Blocking the combination of PD-1 and PD-L1 can effectively prevent the generation of T ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K47/12A61K47/26A61K47/02
CPCC07K16/2818A61K39/395A61K47/12A61K47/26A61K47/02A61K2039/505A61K39/39591A61K9/0019A61K9/19A61K47/183A61K9/08C07K2317/94
Inventor 方源韩冬梅
Owner SHANGHAI HENLIUS BIOTECH INC
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