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Lyophilized formulatons of engineered anti-il-23p19 antibodies

一种il-23p19、冻干制剂的技术，应用在抗炎剂、抗病毒剂、冻干输送等方向，能够解决过敏反应、致命、治疗效果降低等问题

Active Publication Date: 2011-09-28
MERCK SHARP & DOHME BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because most monoclonal antibodies are derived from non-human species, multiple uses in humans lead to the generation of an immune response against the therapeutic antibody
This type of immune response results in a minimal reduction in the effectiveness of the treatment and can lead to a fatal allergic reaction

Method used

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  • Lyophilized formulatons of engineered anti-il-23p19 antibodies
  • Lyophilized formulatons of engineered anti-il-23p19 antibodies
  • Lyophilized formulatons of engineered anti-il-23p19 antibodies

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] Lyophilized formulation of humanized anti-IL-23p19 antibody.

[0108] Lyophilized formulations of humanized anti-IL-23p19 antibodies were prepared as follows. Table 3 provides the batch formula of the humanized anti-IL-23p19 antibody. The final concentration of humanized anti-IL-23p19 antibody was 25 mg / mL. This batch formulation can be used to prepare lyophilized 50 mg / vial units as described in Table 4 below. Uses polysorbate-80 from plant sources. Additional citric acid or sodium hydroxide can be added to adjust the pH to the desired value of about 4.8 (±0.2). Use pH 4.8 to reduce opalescence when antibodies are reconstituted from pH 5.5-5.6 citrate buffer. Use Sterile Water for Injection (WFI) to bring the ingredients to a final volume of 40 L. Of course, correspondingly smaller batches could be prepared by proportionally reducing the amounts listed in Table 3.

[0109] table 3

[0110] Batch formulation of anti-IL-23p19 antibody

[0111] Element

...

Embodiment 2

[0129] Stability testing of lyophilized preparations of humanized anti-IL-23p19 antibody.

[0130] Figure 2-7 The test results of the stability of the lyophilized preparation of the humanized anti-human IL-23p19 antibody under different storage conditions are provided. Some vials are stored in upright and inverted configurations, as shown in the figure. As described in more detail below, Figure 2-4 demonstrated stability of at least 18 months for antibodies lyophilized at pH 5.5 (citrate buffer), Figure 5-7 Antibodies lyophilized at pH 4.8 (citrate buffer) were shown to have a stability of at least 12 months, with 18 and 12 months being the longest time points shown and not the stability endpoints determined by the assay.

[0131] Stability was evaluated as follows. Samples were lyophilized in 5 mL Type I glass vials, sealed with 13 mm bromobutyl lyophilization stoppers (Helvoet Rubber & Plastic Technologies BV, Hellevoetsluis, The Netherlands) and aluminum snap-off cap...

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Abstract

The present invention provides lyophilized formulations of antibodies, such as antibodies that specifically bind to human interleukin-23 p19 (IL-23p19), or antigen binding fragments thereof.

Description

technical field [0001] The present invention generally relates to lyophilized formulations of therapeutic antibodies. Background technique [0002] Interleukin-23 (IL-23) is a heterodimeric cytokine composed of 2 subunits (p19 unique to IL-23 and p40 shared with IL-12). The p19 subunit is structurally related to the p35 subunit of IL-6, granulocyte colony stimulating factor (G-CSF) and IL-12. IL-23 mediates signal transduction through binding to a heterodimeric receptor consisting of IL-23R and IL-12β1 shared with the IL-12 receptor. Numerous earlier studies demonstrated that the consequences of genetic defects in p40 (p40 knockout mice; p40KO mice) were more severe than those found in p35KO mice. Some of these results are finally explained by the discovery of IL-23 and the discovery that p40KO blocks the expression of not only IL-12 but also IL-23. See, e.g., Oppmann et al. (2000) Immunity 13:715-725; Wiekowski et al. (2001) J. Immunol. 166:7563-7570; Parham et al. (2002...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/19A61K47/12A61K47/26C07K16/24
CPCA61K47/12A61K47/26C07K16/244A61K9/19A61K39/39591C07K2317/24A61P1/00A61P1/04A61P17/06A61P19/02A61P25/00A61P27/02A61P29/00A61P31/04A61P31/10A61P31/12A61P35/00A61P37/02A61P37/06A61P3/10Y02A50/30
Inventor 李旭红R·S·卡施A·巴卡
Owner MERCK SHARP & DOHME BV