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Removal promoters and inhibitor for apoptosis cells in vivo 実績あり

外国特許コード F110003487
整理番号 A131-11EP
掲載日 2011年6月28日
出願国 欧州特許庁(EPO)
出願番号 02803517
公報番号 1459756
公報番号 1459756
出願日 平成14年11月19日(2002.11.19)
公報発行日 平成16年9月22日(2004.9.22)
公報発行日 平成26年3月26日(2014.3.26)
国際出願番号 JP2002012053
国際公開番号 WO2003043649
国際出願日 平成14年11月19日(2002.11.19)
国際公開日 平成15年5月30日(2003.5.30)
優先権データ
  • 2002JP012053 (2002.11.19) WO
  • 特願2001-354282 (2001.11.20) JP
発明の名称 (英語) Removal promoters and inhibitor for apoptosis cells in vivo 実績あり
発明の概要(英語) The present invention is to provide a removal promoter for apoptotic cells which is capable of immediately removing apoptotic cells in vivo bymacrophages, or a removal inhibitor which inhibits the removal of apoptotic cells in vivo by macrophages.
A removal promoter for apoptotic cells in vivo containing the milk fat globule-EGF factor 8-L (MFG-E8-L), MFG-E8-L mutant having removal promotion action for apoptotic cells in vivo by macrophages, or preferably a recombinant human or mouse MFG-E8-L, or a recombinant human or mouse MFG-E8-L mutant as an active ingredient is prepared.
Such removal promoters specifically bind to apoptotic cells and promote the phagocytosis of apoptotic cells by macrophages by recognizing aminophospholipids such as phosphatidylserine exposed on apoptotic cell surface.
On the other hand, a point mutation (D89E) MFG-E8-L mutant is used as a removal inhibitor.
特許請求の範囲(英語) [claim1]
1. Any one of the following (a) to (f) for use in a treatment of diseases resulting from incomplete phagocytosis of apoptotic cells in vivo by macrophages: (a) MFG-E8-L which has an action to promote phagocytosis by binding to the apoptotic cells; (b) MFG-E8-L mutant which has an action to promote phagocytosis by binding to the apoptotic cells, which is comprised of an amino acid sequence wherein one or more amino acids are deleted, substituted or added in the amino acid sequence comprising MFG-E8-L, and which contains an EGF-2 domain having RGD motif, a proline/threonine-rich domain, and two factor VIII-homologous domains (C1 and C2); (c) the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b), which is enveloped or embedded in liposome; (d) a recombinant vector comprising DNA encoding the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b); (e) a host cell comprising an expression system which can express the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b); or (f) an antibody against the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b).
[claim2]
2. Any one of the following (a) to (f) for use in a treatment of a decline of biodefense mechanism: a) MFG-E8-L which has an action to promote phagocytosis by binding to the apoptotic cells; (b) MFG-E8-L mutant which has an action to promote phagocytosis by binding to the apoptotic cells, which is comprised of an amino acid sequence wherein one or more amino acids are deleted, substituted or added in the amino acid sequence comprising MFG-E8-L, and which contains an EGF-2 domain having RGD motif, a proline/threonine-rich domain, and two factor VIII-homologous domains (C 1 and C2); (c) the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b), which is enveloped or embedded in liposome; (d) a recombinant vector comprising DNA encoding the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b); (e) a host cell comprising an expression system which can express the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b); or (f) an antibody against the MFG-E8-L of the above (a) or the MFG-E8-L mutant of the above (b).
[claim3]
3. The MFG-E8-L or MFG-E8-L mutant for use in a treatment according to claim 1 or 2, which is a recombinant MFG-E8-L or a recombinant MFG-E8-L mutant.
[claim4]
4. The recombinant MFG-E8-L or the recombinant MFG-E8-L mutant for use in a treatment according to claim 3, which is a recombinant human or mouse MFG-E8-L or a recombinant human or mouse MFG-E8-L mutant.
[claim5]
5. The recombinant MFG-E8-L or the recombinant MFG-E8-L mutant for use in a treatment according to claim 3 or 4, which is a translation product in human cells.
[claim6]
6. The recombinant MFG-E8-L for use in a treatment according to any one of claims 3 to 5, which contains an EGF-2 domain having RGD motif, a proline/threonine-rich domain, and two factor VIII-homologous domains (C1 and C2).
[claim7]
7. The antibody for use in a treatment according to claim 1 or 2, which is an anti-MFG-E8-L monoclonal antibody or an anti-MFG-E8-L mutant monoclonal antibody.
[claim8]
8. A detection method for apoptotic cells in vivo wherein a detection agent for apoptotic cells in vivo, which contains a labeled MFG-E8-L or MFG-E8-L mutant having an action to promote phagocytosis of apoptotic cells in vivo by macrophages, or an antibody against them as an active ingredient is used,
wherein the MFG-E8-L mutant is comprised of an amino acid sequence wherein one or more amino acids are deleted, substituted or added in the amino acid sequence comprising MFG-E8-L, and contains an EGF-2 domain having RGD motif, a proline/threonine-rich domain, and two factor VIII-homologous domains (C1 and C2).
[claim9]
9. A screening method for a substance inducing a promotion of phagocytosis or a substance suppressing a promotion of phagocytosis of apoptotic cells in vivo by macrophages wherein MFG-E8-L or a MFG-E8-L mutant having an action to promote phagocytosis of apoptotic cells in vivo by macrophages, or an antibody against them is contacted with a test substance, to evaluate the extent of phagocytosis of apoptotic cells in vivo,
wherein the MFG-E8-L mutant is comprised of an amino acid sequence wherein one or more amino acids are deleted, substituted or added in the amino acid sequence comprising MFG-E8-L, and contains an EGF-2 domain having RGD motif, a proline/threonine-rich domain, and two factor VIII-homologous domains (C 1 and C2).
  • 出願人(英語)
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • 発明者(英語)
  • NAGATA SHIGEKAZU
国際特許分類(IPC)
欧州特許分類/主・副
  • C07K014/705
  • K61K038/00
指定国 Contracting States: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LI LU MC NL PT SE SK TR
参考情報 (研究プロジェクト等) CREST Structure and Function of Genomes AREA
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