Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof

A specific, antibody technology, applied in the direction of antibody, receptor/cell surface antigen/cell surface determinant, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve unclear MMP-inducing activity How to correlate and the degree of correlation to avoid side effects

Inactive Publication Date: 2007-11-21
伊沃詹尼克斯有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CD147 has also been shown to have homotypic adhesive properties, but it is unclear how and to what extent this is related to its MMP-inducing activity

Method used

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  • Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof
  • Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof
  • Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0232] Example 1: Humanization of murine antibody Hab18

[0233] Based on the teachings of US Patent Application Publication No. US 2003 / 0039649 (Foote) and PCT Application Publication No. WO 04 / 006955 (Foote) and by Tan et al. (2002) and Hwang et al. (2005b) and the present Application to further elucidate the method for superhumanizing the murine Hab18 antibody by determining the canonical structure of the CDRs of the heavy and light chains TM .

[0234] First, based on the teachings of U.S. Patent Application Serial No. 10 / 194975 and U.S. Patent No. 6,681,557 and by Tan et al. (2002. J. Immunol. 169(2): 1119-25) and Hwang et al. ( 2005b) and the method further elucidated in this application (see above), the canonical structures of the heavy and light chain CDRs were determined by examining their sequences as follows. For the sequences below, the upper row shows the Kabat number for each residue and the lower row shows the one-letter amino acid code for each residue.

[0...

Embodiment 2

[0254] Example 2: Binding affinity of humanized Habl8 scFv fragments

[0255] Transhumanization TM Whether the process was successful in altering binding affinity, the following superhumanization was constructed by gene synthesis methods (Stemmer et al., 1995. Gene 16:49-53) TM Single-chain variable region fragments:

[0256] scFv-1 (SEQ ID NO:68): The humanized heavy chain sequence shown in SEQ ID NO:20 was combined with the humanized light chain sequence shown in SEQ ID NO:66.

[0257] scFv-2 (SEQ ID NO: 69): The humanized heavy chain sequence shown in SEQ ID NO: 20 was combined with the humanized light chain sequence shown in SEQ ID NO: 67.

[0258] superhumanized TM Heavy chain, superhumanized TM light chains and the one linking them with (G 4 S 3 ) motif (Huston et al., 1988) consisting of a 15-residue junction region (Huston et al., 1988) assembled using NcoI, BamHI and NotI restriction at the start of the heavy chain, in the junction region and at the end of the l...

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PUM

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Abstract

Antibodies, humanized antibodies, super-humanizedTM antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with or without cytotoxic agents, which specifically bind to hepatocellular cancers and other cancers, and reduce the survival of such target cells, are provided. Said antibodies and fragments thereof may be used in the treatment of patients with tumors that express elevated levels of the antigen, such as hepatocellular carcinoma.

Description

technical field [0001] The present invention relates to antibodies and antibody fragments that bind to CD147, and their use for treating cancer cells expressing CD147. More specifically, the invention relates to non-human antibodies and antibody fragments that have been mutated to reduce their immunogenicity in humans. Background technique [0002] Primary liver cancer - hepatocellular carcinoma (HCC) - is the fourth most common type of cancer worldwide, responsible for approximately 1.3 million deaths per year (Venook, 2000). The number of deaths ranges from 17,000 cases per year in the United States to more than 250,000 cases per year in China. With approximately four million Americans currently infected with epidemic hepatitis C, the number of deaths in the United States is expected to increase dramatically over the next 10-20 years. Because HCC is usually not detected in its advanced stages, it is one of the most lethal forms of cancer, with patients surviving an avera...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/18C07K7/08A61K39/395C07K14/705A61P1/16C07K16/30C07H21/04C12N15/85C07K7/06
CPCC07K16/2803C07K2317/34C07K2317/622C07K2317/92C07K14/70503C07K2317/56C07K2317/24A61P1/16
Inventor V·巴特瑞D·S·威尔森
Owner 伊沃詹尼克斯有限公司
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