Title:
sc(Fv)2 STRUCTURAL ISOMERS
Document Type and Number:
WIPO Patent Application WO/2006/106903
Kind Code:
A1
Abstract:
By separating structural isomers from a human Mp1 antibody and humanized antihuman Mp1 antibody composition and cleaving linkers in the obtained structural isomers, it is confirmed that these structural isomers are in the single chain diabody type and the bivalent scFv type. It is also clarified that these structural isomers are largely different from each other in agonistic activity. Furthermore, it is clarified that the ratio of the structural isomers contained in the sc(Fv)2 composition can be controlled depending on a change in temperature or modification in the sc(Fv)2 linker length and modification in the amino acids in the variable domain.
Inventors:
IGAWA TOMOYUKI (JP)
TSUNODA HIROYUKI (JP)
KOGA AKIKO (JP)
KIKUCHI YASUFUMI (JP)
TSUNODA HIROYUKI (JP)
KOGA AKIKO (JP)
KIKUCHI YASUFUMI (JP)
Application Number:
PCT/JP2006/306800
Publication Date:
October 12, 2006
Filing Date:
March 31, 2006
Export Citation:
Assignee:
CHUGAI PHARMACEUTICAL CO LTD (JP)
IGAWA TOMOYUKI (JP)
TSUNODA HIROYUKI (JP)
KOGA AKIKO (JP)
KIKUCHI YASUFUMI (JP)
IGAWA TOMOYUKI (JP)
TSUNODA HIROYUKI (JP)
KOGA AKIKO (JP)
KIKUCHI YASUFUMI (JP)
International Classes:
C12N15/09; A61K39/395; C07K1/14; C07K16/46
Other References:
KIPRIYANOV S.M. ET AL.: "Effect of domain order on the activity of bacterially produced bispecific single-chain Fv antibodies", J. MOL. BIOL., vol. 330, no. 1, 2003, pages 99 - 111, XP004445110
KRIANGKUM J. ET AL.: "Bispecific and bifunctional single chain recombinant antibodies", BIOMOL. ENG., vol. 18, no. 2, 2001, pages 31 - 40, XP004304464
DE JONGE J. ET AL.: "In vivo retargeting of T cell effector function by recombinant bispecific single chain Fv (anti-CD3 x anti-idiotype) induces long-term survival in the murine BCL1 lymphoma model", J. IMMUNOL., vol. 161, no. 3, 1998, pages 1454 - 1461, XP002350359
MALLENDER W.D. ET AL.: "Construction, expression, and activity of a bivalent bispecific single-chain antibody", J. BIOL. CHEM., vol. 269, no. 1, 1994, pages 199 - 206, XP002262643
MACK M. ET AL.: "A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity", PROC. NATL. ACAD. SCI. USA, vol. 92, no. 15, 1995, pages 7021 - 7025, XP000566333
ORITA T. ET AL.: "A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor", BLOOD, vol. 105, no. 2, 15 January 2005 (2005-01-15), pages 562 - 566, XP002377285
KRIANGKUM J. ET AL.: "Bispecific and bifunctional single chain recombinant antibodies", BIOMOL. ENG., vol. 18, no. 2, 2001, pages 31 - 40, XP004304464
DE JONGE J. ET AL.: "In vivo retargeting of T cell effector function by recombinant bispecific single chain Fv (anti-CD3 x anti-idiotype) induces long-term survival in the murine BCL1 lymphoma model", J. IMMUNOL., vol. 161, no. 3, 1998, pages 1454 - 1461, XP002350359
MALLENDER W.D. ET AL.: "Construction, expression, and activity of a bivalent bispecific single-chain antibody", J. BIOL. CHEM., vol. 269, no. 1, 1994, pages 199 - 206, XP002262643
MACK M. ET AL.: "A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity", PROC. NATL. ACAD. SCI. USA, vol. 92, no. 15, 1995, pages 7021 - 7025, XP000566333
ORITA T. ET AL.: "A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor", BLOOD, vol. 105, no. 2, 15 January 2005 (2005-01-15), pages 562 - 566, XP002377285
Attorney, Agent or Firm:
Shimizu, Hatsushi (1-1-1 Oroshi-machi, Tsuchiura-sh, Ibaraki 47, JP)
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