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Il-33 antagonist-containing therapeutic agent for endometriosis

A technology for endometriosis, applied in medical preparations containing active ingredients, medical preparations with non-active ingredients, anti-animal/human immunoglobulin, etc., can solve uninvestigated endometriosis To achieve the effects of inhibiting fibrosis or proliferation, relieving pain, and inhibiting growth

Pending Publication Date: 2020-05-05
MITSUBISHI TANABE PHARMA CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although Patent Document 1 mentions endometriosis as one of the cases of localized fibrosis, it does not investigate the therapeutic effect of endometriosis in its examples

Method used

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  • Il-33 antagonist-containing therapeutic agent for endometriosis
  • Il-33 antagonist-containing therapeutic agent for endometriosis
  • Il-33 antagonist-containing therapeutic agent for endometriosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0142] Example 1: Effect of IL-33 gene defect in endometriosis model

[0143] As an animal model of endometriosis, uterus-transplanted mice administered estrogen were used (Ricci et al., Reprod. Sci. 2011, vol. 18, p614). Using isoflurane (concentration of isoflurane: 3.0%, air flow: 300-400 to maintain anesthesia) on wild-type 6-week-old female Balb / c mice (Charles River, Japan) or Balb / c background IL- 33 knockout mice (Yasuda et al., PNAS, 2012, Vol.109, p3451; Haenuki et al., J. Allergy Clin. Immunol., 2012, Vol.130, p184) (hereinafter referred to as "IL-33KO mice") were performed After inhalation anesthesia was introduced, a small incision was made on the left side of the middle of the lower abdomen of the mouse, and the left and right uteri were pulled out sequentially from the laparotomy hole, and the ovaries attached to the front end of the uterus were removed. For these mice, 0.5 μg / 100 μL / body corn oil for subcutaneous injection (Wako Junyaku Kogyo) was subcutaneo...

Embodiment 2

[0145] Example 2: Effect of administration of IL-33 on endometriosis model

[0146] A wild-type 6-week-old female Balb / c mouse was used to prepare an endometriosis model by the method described in Example 1. In the IL-33 administration group, recombinant human IL-33 dissolved in PBS was intraperitoneally administered 1 time at 100 ng / 200 μL / body, 3 times / week, 2 weeks, and 6 times in total from the time of implantation of the uterus protein (residue 112-residue 270) (Kondo et al., Int. Immunol. 2008, vol. 20, p791). Two weeks after the transplantation, the mice were euthanized, the abdomen was opened, and the cyst lesions formed in the abdominal cavity were excised, and the respective volumes were measured. like figure 2 As shown, the volume of the cyst lesion was significantly increased in the human IL-33-administered group compared with the vehicle-administered group. This result shows that IL-33 is involved in the growth of cystic lesions. In addition, the concentrat...

Embodiment 3

[0147] Example 3: IL-33 antagonists

[0148] Five kinds of human anti-IL-33 antibodies (A10-1C04, A23-1A05, A25-2C02, A25-3H04, A26-1F02) and fusion proteins formed by mouse ST2 and human IgG1 constant region were prepared using recombinant CHO cells. Mouse sST2-Fc (International Publication No. 2015 / 099175). Their amino acid sequences are shown in the table below. The affinity of the five human anti-IL-33 antibodies to human IL-33 protein (residue 112-residue 270) (ATGen, ILC0701) was determined by KinExA. As a result, A10 Kd=100.3pM in -1C04, Kd=195.3pM in A23-1A05, Kd=700fM in A25-2C02, Kd=7.7pM in A25-3H04, Kd=5.3pM in A26-1F02.

[0149] [Table 1]

[0150]

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Abstract

To provide a therapeutic agent for endometriosis and adenomyosis. IL-33 was identified as an exacerbating factor in endometriosis and adenomyosis, and an IL-33 antagonist, which is capable of inhibiting the function of IL-33, was found to be useful for treating, preventing or alleviating endometriosis and uterine adenomyosis.

Description

technical field [0001] The present invention relates to a therapeutic agent for endometriosis comprising an interleukin-33 (IL-33) antagonist as an active ingredient. Background technique [0002] Endometriosis is a benign (noncancerous) disease in which endometrial tissue proliferates (ectopically) away from the uterine cavity, afflicting approximately 10% of all women of reproductive age. Between 25 and 50% of infertile women suffer from endometriosis. [0003] There are various theories about the cause of endometriosis, but one of the causes is considered to be that endometrial cells reach other tissues along with menstrual blood, and endometrial tissue forms and proliferates ectopically. [0004] Adenomyosis is a disease in which lesions similar to endometrium are observed in the myometrium. Although it is a disease with histological similarities to endometriosis, it is treated as a different disease because of its different pathogenesis and clinical picture. The peak...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K38/17A61K39/395A61K47/68A61P15/00C07K16/24C07K19/00C12N15/113
CPCA61K38/17A61K45/00A61K47/68A61P15/00C07K19/00C12N15/113C07K16/244A61K2039/505C07K2317/76C07K2319/30C07K14/7155A61K39/395
Inventor 善本知广J·M·帕伦博I·V·斯通加藤彻安田好文
Owner MITSUBISHI TANABE PHARMA CORP
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