TOP > 外国特許検索 > COMPOSITION FOR NEUTRALIZING BOTULINUS TOXIN TYPE-A, AND HUMAN ANTI-BOTULINUS TOXIN TYPE-A ANTIBODY

COMPOSITION FOR NEUTRALIZING BOTULINUS TOXIN TYPE-A, AND HUMAN ANTI-BOTULINUS TOXIN TYPE-A ANTIBODY UPDATE

外国特許コード F110002652
整理番号 S2008-0274-C0
掲載日 2011年4月6日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2009JP000250
国際公開番号 WO 2009096162
国際出願日 平成21年1月23日(2009.1.23)
国際公開日 平成21年8月6日(2009.8.6)
優先権データ
  • 特願2008-017152 (2008.1.29) JP
発明の名称 (英語) COMPOSITION FOR NEUTRALIZING BOTULINUS TOXIN TYPE-A, AND HUMAN ANTI-BOTULINUS TOXIN TYPE-A ANTIBODY UPDATE
発明の概要(英語) Disclosed is a means which is effective for botulism diseases and the prevention of the botulism diseases. Specifically disclosed are multiple human anti-botulinus toxin type-A antibodies having different epitopes from one another. Also specifically disclosed is a composition for neutralizing botulinus toxin type-A, which comprises a combination of two or more of the antibodies and which has a high neutralizing activity.
従来技術、競合技術の概要(英語) BACKGROUND ART
Clostridial, toxin is produced by botulinum (Clostridium botulinum), depending on the difference in serotypes classified into type A - g. A, B, E, toxin type F is a significant impact on human health. Human botulism diseases include '(botulinum food poisoning) dietary botulinum disease', 'infant botulinum disease', 'wound botulinum disease' and, 'botulinum infection disease' types of 4. Botulinum toxin type A is involved in 26% of food poisoning. Botulinum toxin type A is involved in 26% of food poisoning. B, and this was followed by the type E, botulinum toxin type F ratio for participation of the food poisoning is relatively low. In addition, wound botulism toxin type B or type A is caused only by have been reported (non-patent document 1).
Adult botulinum food poisoning is usually, proliferation of fungi and spores in food as a result, be orally ingested toxin produced andcorticosteroids on the other hand, in the neonatal botulinum A, food products such as honey present in fungi and spores be orally ingested as a result, the intestinal tract to develop bacteria, growth and toxin production by poisoning symptoms. Somewhat vary depending on the country and the cause of food poisoning toxin type A, type B and type E by cases have been reported. The majority of the infant type A botulinum A, B-type system, by C. butiricum toxin type E, type F is a report by the toxin.
Botulinum toxin heavy chain and light chain S-S bond (disulfide bond) is a structure of a molecule. Botulinum toxin blocks the neurotransmission to muscles, thereby causing flaccid paralysis. Botulinum toxin into the airway or respiratory muscles cause breathing disorders and lethality. 12% And mortality due to botulism, a particular risk group further includes a high mortality rate (non-patent document 3).
On the other hand, the botulinum toxin is the most lethal biological toxins as the toxin (70 kg toxin type A in purified human lethal dose, in intravenous or intramuscular 0.09-0. , 0.70-0. 90µ inhalation; g, even orally 70μg since (JAMA. 2001 Feb 28;285 (8): 1059-70), as the side surfaces of the normal poisoning, bio-terrorism that is used in a specialty, both socially has attracted attention.
Botulinum toxin neutralizer for those which are approved in Japan as, formulation as a raw material and horse serum. The formulation comprises horse serum-derived immunoglobulin, that is predominantly used as heterologous proteins in humans, such as anaphylactic reactions is at risk of causing an immune reaction. In addition, unknown viral infections or serum is also problematic. Further, it is difficult to stably supply. Further, 1 or more years for manufacture of the formulation are necessary, such as bio-terrorism and it is difficult to cope with the emergency. In addition, the problem of husbandry Horse stocking the dosage form is not suitable for the purpose.
With respect to the infant botulinum diseases, such as anaphylactic reactions in order to avoid serious side effects, this horse globulin formulation treatment has not been performed in. In the United States, and normal healthy people neutralizing antibody titers obtained were immunized with higher plasma prepared from human globulin formulation using, for infant botulinum A performed specific therapy. In fact, under the trade name 'BabyBIG', by the subject of pharmaceutical botulinum infant FDA orphan drug approval in manufactured as United States approved. However, the method includes, in addition to the ethical problem and the problem of biohazard available raw materials, further from the viewpoint of securing safety at the time of manufacturing the virus inspection is required to perform various problem will occur. In addition, in Japan the dosage not approved cannot be used.
Toxin type A in the production of the chimeric antibody to recombinant neutralizing success was reported (Patent Document 1). However, in the case of using the antibody, the appearance of HACA (human anti-chimeric antibody) and the problem of, solve a problem such as anaphylactic reaction is necessary. On the other hand, a bio-terrorism threats in the United States in particular toxin-neutralizing also in the sense of have been researched and developed, botulinum toxin B pentamer were immunized human phage antibody libraries were made from lymphocytes, from among the method for selecting the desired fully human neutralizing antibodies have been attempted. However, the toxin type A, exhibit neutralizing activity alone may be sufficient for the acquisition of the antibody clones have not been successful. Therefore, phage obtained as a result of one human 1 antibody, 1 clones from one XENO mice, further immunization of mice obtained from the mouse antibody is humanized by mixing enhanced neutralizing activity (oligoclonal-) is required and thus, the desired purpose, i.e. completely neutralization of toxin by the human neutralizing antibodies, in order to achieve yet developed (Patent Document 2, 3, Non-Patent Document 4, 5, 6).
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • Institute for Antibodies Co., Ltd.
  • JAPAN as represented by DIRECTOR-GENERAL of National Institute of Infectious Diseases
  • OSAKA PREFECTURE UNIVERSITY PUBLIC CORPORATION
  • 発明者(英語)
  • AZUMA, Masachika
  • TAKAHASHI, Motohide
  • KOZAKI, Shunji
  • MUKAMOTO, Masafumi
  • KOHDA, Tomoko
  • KUROSAWA, Gene
  • KUROSAWA, Yoshikazu
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PG PH PL PT RO RS RU SC SD SE SG SK SL SM ST SV SY TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

PAGE TOP

close
close
close
close
close
close