Title:
複雑性が増大した生理活性アセンブリーを生成するための方法および組成物ならびに使用
Document Type and Number:
Japanese Patent JP2009517337
Kind Code:
A
Abstract:
The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.
Inventors:
Chang, Chen-Shin
David M, Goldenberg
McBride, William Jay
Rossi, Edmund A
David M, Goldenberg
McBride, William Jay
Rossi, Edmund A
Application Number:
JP2008536564A
Publication Date:
April 30, 2009
Filing Date:
June 29, 2006
Export Citation:
Assignee:
IBC PHARMACEUTICALS,INC.
International Classes:
A61K39/395; A61K45/00; A61K45/06; A61P1/04; A61P1/06; A61P3/10; A61P5/00; A61P7/00; A61P7/02; A61P7/06; A61P9/12; A61P11/00; A61P11/06; A61P13/12; A61P17/00; A61P17/06; A61P19/00; A61P19/02; A61P21/00; A61P21/04; A61P25/00; A61P25/28; A61P27/02; A61P27/06; A61P31/00; A61P35/00; A61P37/00; A61P37/06; C07K7/06; C07K7/08
Foreign References:
| US4868109A | 1989-09-19 | |||
| US20030232420A1 | 2003-12-18 | |||
| WO2004072287A1 | 2004-08-26 |
Other References:
JPN6011055448; ＳＨＡＲＫＥＹ，Ｒ．Ｍ． ｅｔ ａｌ: 'Ｏｐｔｉｍｉｚｉｎｇ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｐｒｅｔａｒｇｅｔｉｎｇ ｆｏｒ ｕｓｅ ｉｎ ｒａｄｉｏｉｍｍｕｎｏｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８９７Ｓ-９１３Ｓ
JPN6011055452; ＲＯＳＳＩ，Ｅ．Ａ． ｅｔ ａｌ: 'Ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｎｅｗ ｍｕｌｔｉｖａｌｅｎｔ-ｂｉｓｐｅｃｉｆｉｃ ａｇｅｎｔｓ ｆｏｒ ｐｒｅｔａｒｇｅｔｉｎｇ ｔｕｍｏｒ ｌｏｃａｌｉｚａｔｉｏｎ ａｎｄ ｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８８６Ｓ-９６Ｓ
JPN6011055454; ＢＡＮＫＹ，Ｐ． ｅｔ ａｌ: 'Ｄｉｍｅｒｉｚａｔｉｏｎ／ｄｏｃｋｉｎｇ ｄｏｍａｉｎ ｏｆ ｔｈｅ ｔｙｐｅ Ｉａｌｐｈａ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ．' Ｊ Ｂｉｏｌ Ｃｈｅｍ Ｖｏｌ．２７３， Ｎｏ．５２, 1998, ｐ．３５０４８-５５
JPN6011055457; ＯＹＥＮ，Ｏ． ｅｔ ａｌ: 'Ｈｕｍａｎ ｔｅｓｔｉｓ ｃＤＮＡ ｆｏｒ ｔｈｅ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ＲＩＩ ａｌｐｈａ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ ｅｎｃｏｄｅｓ ａｎ ａ' ＦＥＢＳ Ｌｅｔｔ Ｖｏｌ．２４６， Ｎｏ．１-２, 1989, ｐ．５７-６４
JPN6011055460; ＰＬＵＣＫＴＨＵＮ，Ａ． ｅｔ ａｌ: 'Ｎｅｗ ｐｒｏｔｅｉｎ ｅｎｇｉｎｅｅｒｉｎｇ ａｐｐｒｏａｃｈｅｓ ｔｏ ｍｕｌｔｉｖａｌｅｎｔ ａｎｄ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｆｒａｇｍｅｎｔｓ' Ｉｍｍｕｎｏｔｅｃｈｎｏｌｏｇｙ Ｖｏｌ．３， Ｎｏ．２, 1997, ｐ．８３-１０５
JPN6011055462; ＺＨＡＮＧ，Ｙ． ｅｔ ａｌ: 'Ｉｎｔｒａｖｅｎｏｕｓ ＲＮＡ ｉｎｔｅｒｆｅｒｅｎｃｅ ｇｅｎｅ ｔｈｅｒａｐｙ ｔａｒｇｅｔｉｎｇ ｔｈｅ ｈｕｍａｎ ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ ｐｒｏｌｏ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．１０， Ｎｏ．１１, 2004, ｐ．３６６７-７７
JPN6011055433; ＤＥＹＥＶ，Ｓ．Ｍ． ｅｔ ａｌ: 'Ｄｅｓｉｇｎ ｏｆ ｍｕｌｔｉｖａｌｅｎｔ ｃｏｍｐｌｅｘｅｓ ｕｓｉｎｇ ｔｈｅ ｂａｒｎａｓｅ＊ｂａｒｓｔａｒ ｍｏｄｕｌｅ' Ｎａｔ Ｂｉｏｔｅｃｈｎｏｌ Ｖｏｌ．２１， Ｎｏ．１２, 2003, ｐ．１４８６-９２
JPN6011055434; ＢＡＮＫＹ，Ｐ． ｅｔ ａｌ: 'Ｒｅｌａｔｅｄ ｐｒｏｔｅｉｎ-ｐｒｏｔｅｉｎ ｉｎｔｅｒａｃｔｉｏｎ ｍｏｄｕｌｅｓ ｐｒｅｓｅｎｔ ｄｒａｓｔｉｃａｌｌｙ ｄｉｆｆｅｒｅｎｔ ｓｕｒｆａｃｅ ｔｏｐｏｇｒａｐｈｉｅｓ ｄｅｓｐｉ' Ｊ Ｍｏｌ Ｂｉｏｌ Ｖｏｌ．３３０， Ｎｏ．５, 2003, ｐ．１１１７-２９
JPN6011055436; ＮＥＷＬＯＮ，Ｍ．Ｇ． ｅｔ ａｌ: 'Ｔｈｅ ｍｏｌｅｃｕｌａｒ ｂａｓｉｓ ｆｏｒ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ Ａ ａｎｃｈｏｒｉｎｇ ｒｅｖｅａｌｅｄ ｂｙ ｓｏｌｕｔｉｏｎ ＮＭＲ' Ｎａｔ Ｓｔｒｕｃｔ Ｂｉｏｌ Ｖｏｌ．６， Ｎｏ．３, 1999, ｐ．２２２-７
JPN6011055438; ＡＬＴＯ，Ｎ．Ｍ． ｅｔ ａｌ: 'Ｂｉｏｉｎｆｏｒｍａｔｉｃ ｄｅｓｉｇｎ ｏｆ Ａ-ｋｉｎａｓｅ ａｎｃｈｏｒｉｎｇ ｐｒｏｔｅｉｎ-ｉｎ ｓｉｌｉｃｏ： ａ ｐｏｔｅｎｔ ａｎｄ ｓｅｌｅｃｔｉｖｅ ｐｅｐｔｉｄｅ ａｎｔａｇｏｎ' Ｐｒｏｃ Ｎａｔｌ Ａｃａｄ Ｓｃｉ Ｕ Ｓ Ａ Ｖｏｌ．１００， Ｎｏ．８, 2003, ｐ．４４４５-５０
JPN6011055441; ＬＥＯＮ，Ｄ．Ａ． ｅｔ ａｌ: 'Ａ ｓｔａｂｌｅ ａｌｐｈａ-ｈｅｌｉｃａｌ ｄｏｍａｉｎ ａｔ ｔｈｅ Ｎ ｔｅｒｍｉｎｕｓ ｏｆ ｔｈｅ ＲＩａｌｐｈａ ｓｕｂｕｎｉｔｓ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉ' Ｊ Ｂｉｏｌ Ｃｈｅｍ Ｖｏｌ．２７２， Ｎｏ．４５, 1997, ｐ．２８４３１-７
JPN6011055444; ＢＵＲＮＳ-ＨＡＭＵＲＯ，Ｌ．Ｌ． ｅｔ ａｌ: 'Ｄｅｓｉｇｎｉｎｇ ｉｓｏｆｏｒｍ-ｓｐｅｃｉｆｉｃ ｐｅｐｔｉｄｅ ｄｉｓｒｕｐｔｏｒｓ ｏｆ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ Ａ ｌｏｃａｌｉｚａｔｉｏｎ' Ｐｒｏｃ Ｎａｔｌ Ａｃａｄ Ｓｃｉ Ｕ Ｓ Ａ Ｖｏｌ．１００， Ｎｏ．７, 2003, ｐ．４０７２-７
JPN6011055446; ＺＨＡＮＧ，Ｙ． ｅｔ ａｌ: 'Ｎｅｕｒｏｐｒｏｔｅｃｔｉｏｎ ｉｎ ｔｒａｎｓｉｅｎｔ ｆｏｃａｌ ｂｒａｉｎ ｉｓｃｈｅｍｉａ ａｆｔｅｒ ｄｅｌａｙｅｄ ｉｎｔｒａｖｅｎｏｕｓ ａｄｍｉｎｉｓｔｒａｔｉｏｎ ｏｆ ｂｒａｉｎ-' Ｓｔｒｏｋｅ Ｖｏｌ．３２， Ｎｏ．６, 2001, ｐ．１３７８-８４
JPN6011055448; ＳＨＡＲＫＥＹ，Ｒ．Ｍ． ｅｔ ａｌ: 'Ｏｐｔｉｍｉｚｉｎｇ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｐｒｅｔａｒｇｅｔｉｎｇ ｆｏｒ ｕｓｅ ｉｎ ｒａｄｉｏｉｍｍｕｎｏｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８９７Ｓ-９１３Ｓ
JPN6011055452; ＲＯＳＳＩ，Ｅ．Ａ． ｅｔ ａｌ: 'Ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｎｅｗ ｍｕｌｔｉｖａｌｅｎｔ-ｂｉｓｐｅｃｉｆｉｃ ａｇｅｎｔｓ ｆｏｒ ｐｒｅｔａｒｇｅｔｉｎｇ ｔｕｍｏｒ ｌｏｃａｌｉｚａｔｉｏｎ ａｎｄ ｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８８６Ｓ-９６Ｓ
JPN6011055454; ＢＡＮＫＹ，Ｐ． ｅｔ ａｌ: 'Ｄｉｍｅｒｉｚａｔｉｏｎ／ｄｏｃｋｉｎｇ ｄｏｍａｉｎ ｏｆ ｔｈｅ ｔｙｐｅ Ｉａｌｐｈａ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ．' Ｊ Ｂｉｏｌ Ｃｈｅｍ Ｖｏｌ．２７３， Ｎｏ．５２, 1998, ｐ．３５０４８-５５
JPN6011055457; ＯＹＥＮ，Ｏ． ｅｔ ａｌ: 'Ｈｕｍａｎ ｔｅｓｔｉｓ ｃＤＮＡ ｆｏｒ ｔｈｅ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ＲＩＩ ａｌｐｈａ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ ｅｎｃｏｄｅｓ ａｎ ａ' ＦＥＢＳ Ｌｅｔｔ Ｖｏｌ．２４６， Ｎｏ．１-２, 1989, ｐ．５７-６４
JPN6011055460; ＰＬＵＣＫＴＨＵＮ，Ａ． ｅｔ ａｌ: 'Ｎｅｗ ｐｒｏｔｅｉｎ ｅｎｇｉｎｅｅｒｉｎｇ ａｐｐｒｏａｃｈｅｓ ｔｏ ｍｕｌｔｉｖａｌｅｎｔ ａｎｄ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｆｒａｇｍｅｎｔｓ' Ｉｍｍｕｎｏｔｅｃｈｎｏｌｏｇｙ Ｖｏｌ．３， Ｎｏ．２, 1997, ｐ．８３-１０５
JPN6011055462; ＺＨＡＮＧ，Ｙ． ｅｔ ａｌ: 'Ｉｎｔｒａｖｅｎｏｕｓ ＲＮＡ ｉｎｔｅｒｆｅｒｅｎｃｅ ｇｅｎｅ ｔｈｅｒａｐｙ ｔａｒｇｅｔｉｎｇ ｔｈｅ ｈｕｍａｎ ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ ｐｒｏｌｏ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．１０， Ｎｏ．１１, 2004, ｐ．３６６７-７７
JPN6011055452; ＲＯＳＳＩ，Ｅ．Ａ． ｅｔ ａｌ: 'Ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｎｅｗ ｍｕｌｔｉｖａｌｅｎｔ-ｂｉｓｐｅｃｉｆｉｃ ａｇｅｎｔｓ ｆｏｒ ｐｒｅｔａｒｇｅｔｉｎｇ ｔｕｍｏｒ ｌｏｃａｌｉｚａｔｉｏｎ ａｎｄ ｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８８６Ｓ-９６Ｓ
JPN6011055454; ＢＡＮＫＹ，Ｐ． ｅｔ ａｌ: 'Ｄｉｍｅｒｉｚａｔｉｏｎ／ｄｏｃｋｉｎｇ ｄｏｍａｉｎ ｏｆ ｔｈｅ ｔｙｐｅ Ｉａｌｐｈａ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ．' Ｊ Ｂｉｏｌ Ｃｈｅｍ Ｖｏｌ．２７３， Ｎｏ．５２, 1998, ｐ．３５０４８-５５
JPN6011055457; ＯＹＥＮ，Ｏ． ｅｔ ａｌ: 'Ｈｕｍａｎ ｔｅｓｔｉｓ ｃＤＮＡ ｆｏｒ ｔｈｅ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ＲＩＩ ａｌｐｈａ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ ｅｎｃｏｄｅｓ ａｎ ａ' ＦＥＢＳ Ｌｅｔｔ Ｖｏｌ．２４６， Ｎｏ．１-２, 1989, ｐ．５７-６４
JPN6011055460; ＰＬＵＣＫＴＨＵＮ，Ａ． ｅｔ ａｌ: 'Ｎｅｗ ｐｒｏｔｅｉｎ ｅｎｇｉｎｅｅｒｉｎｇ ａｐｐｒｏａｃｈｅｓ ｔｏ ｍｕｌｔｉｖａｌｅｎｔ ａｎｄ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｆｒａｇｍｅｎｔｓ' Ｉｍｍｕｎｏｔｅｃｈｎｏｌｏｇｙ Ｖｏｌ．３， Ｎｏ．２, 1997, ｐ．８３-１０５
JPN6011055462; ＺＨＡＮＧ，Ｙ． ｅｔ ａｌ: 'Ｉｎｔｒａｖｅｎｏｕｓ ＲＮＡ ｉｎｔｅｒｆｅｒｅｎｃｅ ｇｅｎｅ ｔｈｅｒａｐｙ ｔａｒｇｅｔｉｎｇ ｔｈｅ ｈｕｍａｎ ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ ｐｒｏｌｏ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．１０， Ｎｏ．１１, 2004, ｐ．３６６７-７７
JPN6011055433; ＤＥＹＥＶ，Ｓ．Ｍ． ｅｔ ａｌ: 'Ｄｅｓｉｇｎ ｏｆ ｍｕｌｔｉｖａｌｅｎｔ ｃｏｍｐｌｅｘｅｓ ｕｓｉｎｇ ｔｈｅ ｂａｒｎａｓｅ＊ｂａｒｓｔａｒ ｍｏｄｕｌｅ' Ｎａｔ Ｂｉｏｔｅｃｈｎｏｌ Ｖｏｌ．２１， Ｎｏ．１２, 2003, ｐ．１４８６-９２
JPN6011055434; ＢＡＮＫＹ，Ｐ． ｅｔ ａｌ: 'Ｒｅｌａｔｅｄ ｐｒｏｔｅｉｎ-ｐｒｏｔｅｉｎ ｉｎｔｅｒａｃｔｉｏｎ ｍｏｄｕｌｅｓ ｐｒｅｓｅｎｔ ｄｒａｓｔｉｃａｌｌｙ ｄｉｆｆｅｒｅｎｔ ｓｕｒｆａｃｅ ｔｏｐｏｇｒａｐｈｉｅｓ ｄｅｓｐｉ' Ｊ Ｍｏｌ Ｂｉｏｌ Ｖｏｌ．３３０， Ｎｏ．５, 2003, ｐ．１１１７-２９
JPN6011055436; ＮＥＷＬＯＮ，Ｍ．Ｇ． ｅｔ ａｌ: 'Ｔｈｅ ｍｏｌｅｃｕｌａｒ ｂａｓｉｓ ｆｏｒ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ Ａ ａｎｃｈｏｒｉｎｇ ｒｅｖｅａｌｅｄ ｂｙ ｓｏｌｕｔｉｏｎ ＮＭＲ' Ｎａｔ Ｓｔｒｕｃｔ Ｂｉｏｌ Ｖｏｌ．６， Ｎｏ．３, 1999, ｐ．２２２-７
JPN6011055438; ＡＬＴＯ，Ｎ．Ｍ． ｅｔ ａｌ: 'Ｂｉｏｉｎｆｏｒｍａｔｉｃ ｄｅｓｉｇｎ ｏｆ Ａ-ｋｉｎａｓｅ ａｎｃｈｏｒｉｎｇ ｐｒｏｔｅｉｎ-ｉｎ ｓｉｌｉｃｏ： ａ ｐｏｔｅｎｔ ａｎｄ ｓｅｌｅｃｔｉｖｅ ｐｅｐｔｉｄｅ ａｎｔａｇｏｎ' Ｐｒｏｃ Ｎａｔｌ Ａｃａｄ Ｓｃｉ Ｕ Ｓ Ａ Ｖｏｌ．１００， Ｎｏ．８, 2003, ｐ．４４４５-５０
JPN6011055441; ＬＥＯＮ，Ｄ．Ａ． ｅｔ ａｌ: 'Ａ ｓｔａｂｌｅ ａｌｐｈａ-ｈｅｌｉｃａｌ ｄｏｍａｉｎ ａｔ ｔｈｅ Ｎ ｔｅｒｍｉｎｕｓ ｏｆ ｔｈｅ ＲＩａｌｐｈａ ｓｕｂｕｎｉｔｓ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉ' Ｊ Ｂｉｏｌ Ｃｈｅｍ Ｖｏｌ．２７２， Ｎｏ．４５, 1997, ｐ．２８４３１-７
JPN6011055444; ＢＵＲＮＳ-ＨＡＭＵＲＯ，Ｌ．Ｌ． ｅｔ ａｌ: 'Ｄｅｓｉｇｎｉｎｇ ｉｓｏｆｏｒｍ-ｓｐｅｃｉｆｉｃ ｐｅｐｔｉｄｅ ｄｉｓｒｕｐｔｏｒｓ ｏｆ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ Ａ ｌｏｃａｌｉｚａｔｉｏｎ' Ｐｒｏｃ Ｎａｔｌ Ａｃａｄ Ｓｃｉ Ｕ Ｓ Ａ Ｖｏｌ．１００， Ｎｏ．７, 2003, ｐ．４０７２-７
JPN6011055446; ＺＨＡＮＧ，Ｙ． ｅｔ ａｌ: 'Ｎｅｕｒｏｐｒｏｔｅｃｔｉｏｎ ｉｎ ｔｒａｎｓｉｅｎｔ ｆｏｃａｌ ｂｒａｉｎ ｉｓｃｈｅｍｉａ ａｆｔｅｒ ｄｅｌａｙｅｄ ｉｎｔｒａｖｅｎｏｕｓ ａｄｍｉｎｉｓｔｒａｔｉｏｎ ｏｆ ｂｒａｉｎ-' Ｓｔｒｏｋｅ Ｖｏｌ．３２， Ｎｏ．６, 2001, ｐ．１３７８-８４
JPN6011055448; ＳＨＡＲＫＥＹ，Ｒ．Ｍ． ｅｔ ａｌ: 'Ｏｐｔｉｍｉｚｉｎｇ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｐｒｅｔａｒｇｅｔｉｎｇ ｆｏｒ ｕｓｅ ｉｎ ｒａｄｉｏｉｍｍｕｎｏｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８９７Ｓ-９１３Ｓ
JPN6011055452; ＲＯＳＳＩ，Ｅ．Ａ． ｅｔ ａｌ: 'Ｄｅｖｅｌｏｐｍｅｎｔ ｏｆ ｎｅｗ ｍｕｌｔｉｖａｌｅｎｔ-ｂｉｓｐｅｃｉｆｉｃ ａｇｅｎｔｓ ｆｏｒ ｐｒｅｔａｒｇｅｔｉｎｇ ｔｕｍｏｒ ｌｏｃａｌｉｚａｔｉｏｎ ａｎｄ ｔｈｅｒａｐｙ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．９， Ｎｏ．１０ Ｐｔ ２, 2003, ｐ．３８８６Ｓ-９６Ｓ
JPN6011055454; ＢＡＮＫＹ，Ｐ． ｅｔ ａｌ: 'Ｄｉｍｅｒｉｚａｔｉｏｎ／ｄｏｃｋｉｎｇ ｄｏｍａｉｎ ｏｆ ｔｈｅ ｔｙｐｅ Ｉａｌｐｈａ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ．' Ｊ Ｂｉｏｌ Ｃｈｅｍ Ｖｏｌ．２７３， Ｎｏ．５２, 1998, ｐ．３５０４８-５５
JPN6011055457; ＯＹＥＮ，Ｏ． ｅｔ ａｌ: 'Ｈｕｍａｎ ｔｅｓｔｉｓ ｃＤＮＡ ｆｏｒ ｔｈｅ ｒｅｇｕｌａｔｏｒｙ ｓｕｂｕｎｉｔ ＲＩＩ ａｌｐｈａ ｏｆ ｃＡＭＰ-ｄｅｐｅｎｄｅｎｔ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ ｅｎｃｏｄｅｓ ａｎ ａ' ＦＥＢＳ Ｌｅｔｔ Ｖｏｌ．２４６， Ｎｏ．１-２, 1989, ｐ．５７-６４
JPN6011055460; ＰＬＵＣＫＴＨＵＮ，Ａ． ｅｔ ａｌ: 'Ｎｅｗ ｐｒｏｔｅｉｎ ｅｎｇｉｎｅｅｒｉｎｇ ａｐｐｒｏａｃｈｅｓ ｔｏ ｍｕｌｔｉｖａｌｅｎｔ ａｎｄ ｂｉｓｐｅｃｉｆｉｃ ａｎｔｉｂｏｄｙ ｆｒａｇｍｅｎｔｓ' Ｉｍｍｕｎｏｔｅｃｈｎｏｌｏｇｙ Ｖｏｌ．３， Ｎｏ．２, 1997, ｐ．８３-１０５
JPN6011055462; ＺＨＡＮＧ，Ｙ． ｅｔ ａｌ: 'Ｉｎｔｒａｖｅｎｏｕｓ ＲＮＡ ｉｎｔｅｒｆｅｒｅｎｃｅ ｇｅｎｅ ｔｈｅｒａｐｙ ｔａｒｇｅｔｉｎｇ ｔｈｅ ｈｕｍａｎ ｅｐｉｄｅｒｍａｌ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ ｐｒｏｌｏ' Ｃｌｉｎ Ｃａｎｃｅｒ Ｒｅｓ Ｖｏｌ．１０， Ｎｏ．１１, 2004, ｐ．３６６７-７７
Attorney, Agent or Firm:
Hajime Tsukuni
Koshiro Tsukuda
Fusayuki Saito
Koshiro Tsukuda
Fusayuki Saito