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
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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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