Anti-cancer treatments with anti-EGFR antibodies having a low fucosylation
An EGFR-, fucose technology, applied in the direction of antibody medical components, antibodies, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve problems such as adverse skin reactions and achieve high therapeutic efficacy , significant treatment characteristics and effects of
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Embodiment approach
[0243] Specific and particularly preferred embodiments of the invention will be described again below:
[0244] In specific embodiments, the fucose-reduced anti-EGFR antibodies of the invention have the following characteristics:
[0245] (i) it comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 or 9 or an amino acid sequence at least 80% identical thereto and comprising CDR1 having the amino acid sequence of SEQ ID NO: 1 , CDR2, which has the amino acid sequence of SEQ ID NO:2, and CDR3, which has the amino acid sequence of SEQ ID NO:3;
[0246] (ii) it comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 8 or 10 or an amino acid sequence at least 80% identical thereto and comprising, CDR1, an amino acid sequence of SEQ ID NO: 4 Sequence, CDR2, which has the amino acid sequence of SEQ ID NO:5, and CDR3, which has the amino acid sequence of SEQ ID NO:6;
[0247] (iii) It has the following glycosylatio...
Embodiment approach 1
[0305] Embodiment 1: An anti-EGFR antibody having a glycosylation site in the CH2 domain, wherein 50% or less of the glycans attached to the glycosylation site carry fucose (reduced fucose anti-EGFR antibody), and wherein the fucose-reduced anti-EGFR antibody is capable of inducing an antibody-dependent cytotoxic response for the treatment of EGFR-positive neoplastic disease in a human patient, wherein the fucose-reduced Anti-EGFR antibodies resulted in grade 3 or higher adverse skin reactions in no more than 10% of treated patients.
Embodiment approach 2
[0306] Embodiment 2 of embodiment 1: an anti-EGFR antibody, wherein the fucose-reduced anti-EGFR antibody results in a grade 3 or higher acneiform rash in no more than 5% of treated patients.
[0307] Embodiment 3 of embodiment 1 or 2: an anti-EGFR antibody for use in the treatment of a human patient suffering from an EGFR positive neoplasia in which at least one other anti-EGFR antibody has been shown to be active in more than 50% of the treated Patients exhibited adverse skin reactions and / or grade 3 or higher adverse skin reactions in at least 12% of patients.
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Application Information
- IPC
- C07K16/28; A61K39/00
- CPC
- C07K16/2863; A61K2039/505; C07K2317/41; C07K2317/732; A61K47/6871; A61P35/00; A61P35/04; A61P43/00
- Inventors
- S·戈勒茨; A·丹尼尔奇克