Humanized and chimeric anti-epidermal growth factor receptor monoclonal antibodies
AssigneeMerck Patent GmbH
InventorsMary M. Bendig, Catherine A. Kettleborough, Jose Saldanha
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Abstract
Humanized and chimeric anti-epidermal growth factor receptor (anti-EGF-R) monoclonal antibodies are disclosed, comprising an artificial modified consensus sequence for the heavy chain of the framework region of the variable region of a human immunoglobulin. Corresponding humanized and chimeric monoclonal antibodies which bind to epitopes of the epidermal growth factor receptor (EGF-R) having specific amino acid sequences in the hypervariable regions responsible for EGF-R binding are also disclosed. These antibodies are therapeutically and diagnostically useful.
Claims22
A humanized antibody, comprising a variable region and a constant region, wherein the hypervariable region of the light chain CDRs has the following amino acid sequences:
- ______________________________________ CDR-1 Ser--Ala--Ser--Ser--Ser--Val--Thr--Tyr--Met--Tyr (SEQ ID NO:1), CDR-2 Asp--Thr--Ser--Asn--Leu--Ala--Ser (SEQ ID NO:2) and CDR-3 Gln--Gln--Trp--Ser--Ser--His--Ile--Phe--Thr (SEQ ID NO:3);
- ______________________________________
- the hypervariable region of the heavy chain CDRs has the following amino acid sequences:
- ______________________________________ CDR-1 Ser--His--Trp--Met--His (SEQ ID NO:4), CDR-2 Glu--Phe--Asn--Pro--Ser--Asn--Gly--Arg--Thr--Asn-- Tyr--Asn--Glu--Lys--Phe--Lys--Ser (SEQ ID NO:5) and CDR-3 Arg--Asp--Tyr--Asp--Tyr--Asp--Gly--Arg--Tyr-- Phe--Asp--Tyr (SEQ ID NO:6);
- ______________________________________
- the light chain framework region has the following amino acid sequences:
- ______________________________________ FR-1 Asp--Ile--Gln--Met--Thr--Gln--Ser--Pro--Ser-- Ser--Leu--Ser--Ala--Ser--Val--Gly--Asp--Arg--Val-- Thr--Ile--Thr--Cys (SEQ ID NO:7), FR-2 Trp--Tyr--Gln--Gln--Lys--Pro--Gly--Lys--Ala-- Pro--Lys--Leu--Leu--Ile--Tyr (SEQ ID NO:8), FR-3 Gly--Val--Pro--Ser--Arg--Phe--Ser--Gly--Ser-- Gly--Ser--Gly--Thr--Asp--Xaa.sub.1 --Thr--Phe--Thr-- Ile--Ser--Ser--Leu--Gln--Pro--Glu--Asp--Ile--Ala-- Thr--Tyr--Tyr--Cys (SEQ ID NO:9) and FR-4 Phe--Gly--Gln--Gly--Thr--Lys--Val--Glu--Ile--Lys (SEQ ID NO:10);
- ______________________________________
- the heavy chain framework region has the following amino acid sequences:
- ______________________________________ FR-1 Gln--Val--Gln--Leu--Val--Gln--Ser--Gly--Ala--Glu-- Val--Lys--Lys--Pro--Gly--Ala--Ser--Val--Lys--Val-- Ser--Cys--Lys--Ala--Ser--Gly--Tyr--Thr--Phe--Xaa.sub.2 (SEQ ID NO:11), FR-2 Trp--Val--Xaa.sub.3 --Gln--Xaa.sub.4 --Xaa.sub.5 --Gly--Gln--Gly-- Leu--Glu--Trp--Xaa.sub.6 --Gly (SEQ ID NO:12), FR-3 Xaa.sub.7 --Xaa.sub.8 --Thr--Met--Thr--Xaa.sub.9 --Asp--Thr--Ser-- Thr--Asn--Thr--Ala--Tyr--Met--Xaa.sub.10 --Leu--Ser--Ser-- Leu--Arg--Ser--Glu--Asp--Thr--Ala--Val--Tyr--Tyr-- Cys--Ala--Ser (SEQ ID NO:13) and Fr-4 Trp--Gly--Gln--Gly--Thr--Leu--Val--Thr--Val--Ser-- Ser (SEQ ID NO:14);
- ______________________________________
- wherein Xaa.sub.1 is Tyr, Phe, Trp or His;
- Xaa.sub.2 is Thr or Ser;
- Xaa.sub.3 is Arg or His;
- Xaa.sub.4 is Ala, Lys or His;
- Xaa.sub.5 is Pro or Val;
- Xaa.sub.6 is Ile, Val or Leu;
- Xaa.sub.7 is Lys, Arg or His;
- Xaa.sub.8 is Ala, Val, Pro or Gly;
- Xaa.sub.9 is Val, Ala, Pro or Gly;
- and Xaa.sub.10 is Glu or Asn;
- and
- wherein said humanized antibody binds to human EGF receptors, and inhibits binding of EGF to EGF-receptor.
The expression vector pRVH425 (DSM 6339).
Dependencies are inferred from the claim text.