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Title:
FUSION PROTEIN, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/217691
Kind Code:
A1
Abstract:
The present invention relates to the field of biological medicines. Disclosed are a fusion protein, and a manufacturing method therefor and an application thereof. The fusion protein comprises a polypeptide specifically binding to a KRas protein, a tumor cell-specific cell penetrating peptide and a lysosome recognition peptide. In the present invention, for the first time, a fusion protein having tumor targeting and penetrability and protein specificity degradation is constructed for an "undruggable" protein design, and a new idea is provided for development of anticancer targeted drugs. The fusion protein can simultaneously induce degradation of wild type and mutant KRas proteins, which is different from the case in the prior art that one molecule can only target one target protein. Moreover, the fusion protein can improve the sensitivity of a KRas mutant tumor on a tumor targeting drug by inducing KRas degradation, thereby expanding the application range of existing anticancer targeting drugs, and the invention has great significance in clinical tumor treatment.

Inventors:
ZENG MUSHENG (CN)
YANG JIE (CN)
FENG GUOKAI (CN)
WANG QIAOLI (CN)
Application Number:
PCT/CN2021/094237
Publication Date:
October 20, 2022
Filing Date:
May 18, 2021
Export Citation:
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Assignee:
UNIV SUN YAT SEN (CN)
SUN YAT SEN UNIV CANCER CENTER SYSUCC (CN)
International Classes:
C07K19/00; A61K38/16; A61P35/00; C12N5/10; C12N15/62; C12N15/63
Domestic Patent References:
WO2019005822A12019-01-03
Foreign References:
CN104797603A2015-07-22
CN104131034A2014-11-05
CN106852148A2017-06-13
Other References:
MA YIHUI, PANG XIA, XU JINGJING, XIA PEIYI, GAO HANQING: "A preliminary study on targeted degradation of KRAS oncoprotein by using a ubiqui- tin-independent, proteasome-mediated degradation pathway "ODC/AZ"", CHINESE JOURNAL OF CLINICAL ONCOLOGY, TIANJIN SHI YIXUE ZAZHISHE, TIANJIN, CH, vol. 43, no. 21, 15 November 2016 (2016-11-15), CH , pages 937 - 942, XP055977017, ISSN: 1000-8179, DOI: 10.3969/j.issn.1000-8179.2016.21.868
MELCHIONNA, T. CATTANEO, A.: "A Protein Silencing Switch by Ligand-induced Proteasome-targeting Intrabodies", JOURNAL OF MOLECULAR BIOLOGY, ACADEMIC PRESS, UNITED KINGDOM, vol. 374, no. 3, 1 November 2007 (2007-11-01), United Kingdom , pages 641 - 654, XP022324999, ISSN: 0022-2836, DOI: 10.1016/j.jmb.2007.09.053
Attorney, Agent or Firm:
JIAQUAN IP LAW (CN)
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