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Title:
FUSION PROTEIN BETWEEN ANTIGEN-BINDING MOLECULE AND STREPTAVIDIN VARIANT
Document Type and Number:
WIPO Patent Application WO/2023/008515
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a fusion protein that is for use in treatment or diagnosis of cancer and that is formed between a molecule recognizing a cancer cell or the like and a streptavidin variant. According to the present invention, provided is a fusion protein in which an antigen-binding molecule having a molecular weight of 20,000 or less is bound to, via a linker sequence, the N-terminal side and/or the C-terminal side of a streptavidin variant, said streptavidin variant containing an amino acid sequence derived from the amino acid sequence of core streptavidin described in SEQ ID NO: 17 (wherein the amino acid sequence of Pro-Ser-Ala-Ala-Ser at the C-terminal may be partially or totally deleted) by the following mutations (1) to (6) and having reduced immunogenicity compared to wild-type streptavidin. (1) A mutation in which tyrosine at the 10th amino acid residue is replaced by serine or threonine. (2) A mutation in which tyrosine at the 71st amino acid residue is replaced by alanine or serine. (3) A mutation in which arginine at the 72nd amino acid residue is replaced by lysine. (4) A mutation in which glutamic acid at the 89th amino acid residue is replaced by aspartic acid. (5) A mutation in which arginine at the 91st amino acid residue is replaced by lysine. (6) A mutation in which glutamic acid at the 104th amino acid residue is replaced by glutamine or asparagine.

Inventors:
TANAKA TOSHIYA (JP)
YAMASHITA TAKEFUMI (JP)
KODAMA TATSUHIKO (JP)
KANAI MOTOMU (JP)
YAMATSUGU KENZO (JP)
TATSUMI TOSHIFUMI (JP)
TAKAHASHI KAZUKI (JP)
SUGIYAMA AKIRA (JP)
TSUKAGOSHI MASANOBU (JP)
CHANSLER MICHAEL (JP)
NAKAI MASANORI (JP)
Application Number:
PCT/JP2022/029073
Publication Date:
February 02, 2023
Filing Date:
July 28, 2022
Export Citation:
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Assignee:
UNIV TOKYO (JP)
SAVID THERAPEUTICS INC (JP)
International Classes:
C12N15/62; A61K31/409; A61K38/16; A61K47/66; A61K49/00; A61P35/00; C07K14/195; C07K16/30; C07K19/00; C12P21/02
Domestic Patent References:
WO2020138427A12020-07-02
WO2020032165A12020-02-13
WO2010095455A12010-08-26
Foreign References:
JP6127045B22017-05-10
JP2017524659A2017-08-31
Other References:
ORLOVA ANNA, ET AL: "Tumor imaging using a picomolar affinity HER2 binding affibody molecule.", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 66, no. 8, 15 April 2006 (2006-04-15), US, pages 4339 - 4348, XP002488605, ISSN: 0008-5472, DOI: 10.1158/0008-5472.CAN-05-3521
SUGIYAMA AKIRA, KAWAMURA TAKESHI, TANAKA TOSHIYA, DOI HIROFUMI, YAMASHITA TAKEFUMI, SHINODA KEIKO, FUJITANI HIDEAKI, YAMATSUGU KEN: "Cupid and Psyche system for the diagnosis and treatment of advanced cancer", PROCEEDINGS OF THE JAPAN ACADEMY. SERIES B, PHYSICAL AND BIOLOGICAL SCIENCES, TOKYO, JP, vol. 95, no. 10, 11 December 2019 (2019-12-11), JP , pages 602 - 611, XP093028615, ISSN: 0386-2208, DOI: 10.2183/pjab.95.041
MULLIGAN ET AL., NATURE, vol. 277, 1979, pages 108
MIZUSHIMA ET AL., NUCLEIC ACIDS RES, vol. 18, 1990, pages 5322
LOFBLOM, J. FEBS LETT, vol. 584, no. 12, 2010, pages 2670 - 80
Attorney, Agent or Firm:
SIKS & CO. (JP)
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