TOP > 外国特許検索 > NOVEL HIGH-FUNCTIONING ENZYME HAVING ALTERED HUMAN β-HEXOSAMINIDASE B SUBSTRATE SPECIFICITY, AND HAVING PROTEASE RESISTANCE APPLIED THERETO

NOVEL HIGH-FUNCTIONING ENZYME HAVING ALTERED HUMAN β-HEXOSAMINIDASE B SUBSTRATE SPECIFICITY, AND HAVING PROTEASE RESISTANCE APPLIED THERETO

外国特許コード F140008026
整理番号 S2013-0022-C0
掲載日 2014年11月19日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2013JP078179
国際公開番号 WO 2014061735
国際出願日 平成25年10月17日(2013.10.17)
国際公開日 平成26年4月24日(2014.4.24)
優先権データ
  • 特願2012-232266 (2012.10.19) JP
発明の名称 (英語) NOVEL HIGH-FUNCTIONING ENZYME HAVING ALTERED HUMAN β-HEXOSAMINIDASE B SUBSTRATE SPECIFICITY, AND HAVING PROTEASE RESISTANCE APPLIED THERETO
発明の概要(英語) Provided is an improved β-subunit of human β-hexosaminidase, having activity derived from a α-subunit of wild-type human β-hexosaminidase, and having resistance to protease. A protein comprising, in the amino acid sequence for a β-subunit of wild-type human β-hexosaminidase, an amino acid sequence in which the 312th-318th amino acids have been substituted, in order, for glycine, serine, glutamic acid, proline, serine, glycine and threonine respectively.
従来技術、競合技術の概要(英語) BACKGROUND ART
- Tailing directional zandohoffu saxophone disease and a disease that is, both, by a decrease in the activity of β - hexosaminidase A (Hex A), neural cell GM2 ganglioside is accumulated to the cranial nerves causing disease symptoms. Is Hex A, α - β - subunit of a heterodimeric subunits and, having an activity of enzymes that degrade the ganglioside GM2. - Tailing directional saxophone is a disease that is, based on the α - subunit Hex A deficiency and deficiency, is a disease that is zandohoffu, based on the subunit β - Hex A deficiency is deficient.
The present inventors discovered that this, with respect to the CHO cell lines and special yeast strain, α - β - subunit and the subunit encoded by the gene (each HEXA cDNA and HEXB cDNA) is inserted into the expression vector is introduced, the wild-type recombinant Hex A to establish a cell line which expresses constantly are. In this method the production of wild-type recombinant Hex A, was administered to mice zandohoffu disease models, GM2 accumulated in the cranial nervous system gangliosides showed an improvement of diarrhea and weight loss, disease - or tailing directional saxophone zandohoffu to check the validity of the disease and enzyme replacement therapies (Patent Document 1; non-patent document 1).
However, in general, an enzyme deficient patient and repeatedly administering the therapeutic agent, therapeutic agent in many cases the enzymes in the body and recognized as foreign, resulting in an antibody is produced, as a result, adverse side reactions such as anaphylactic reactions and allergic reaction appears. Therefore, it is wild-type recombinant Hex A saxophone - tailing directional zandohoffu disease when administered to a patient's disease is, in the same manner as described above, to possibly result in harmful side reactions. In addition, the wild-type recombinant Hex A, low stability in blood (in plasma), organ failure (neural cell) to the cells is a problem of low efficiency of incorporation of the.
In order to solve these problems, the inventors have found that α - β - β - hexosaminidase subunit and of the dimensional structure of the subunit based on the information, the active site of the α - subunit β - subunit was substituted with the active site of a modified β - subunit was produced. Then, this modified β - constitute a sub-unit as a component, a modified homodimer β - hexosaminidase B type (hereinafter, referred to as' ModB ') was prepared, the recombinant enzyme has activity in gangliosides GM2 was confirmed to be (Patent Document 2; non-patent document 2).
  • 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
  • TOKUSHIMA UNIVERSITY
  • MEIJI PHARMACEUTICAL UNIVERSITY
  • 発明者(英語)
  • ITO Koji
  • SAKURABA Hitoshi
  • TSUJI Daisuke
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL 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 IR IS JP KE KG 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 PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL 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 RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN TD TG
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