Recombinant antibodies specific for a growth factor receptor
First Claim
1. A recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the heavy chain variable domain comprises a polypeptide of the formula
wherein FR1 is a polypeptide comprising 25-33 naturally occurring amino acids, FR2 is a polypeptide comprising 12-16 naturally occurring amino acids, FR3 is a polypeptide comprising 30-34 naturally occurring amino acids, FR4 is a polypeptide comprising 6-13 naturally occurring amino acids, CDR1H is a polypeptide of the amino acid sequence 32-36 of SEQ ID NO;
5, CDR2H is a polypeptide of the amino acid sequence 51-67 of SEQ ID NO;
5, CDR3H is a polypeptide of the amino acid sequence 100 to 109 of SEQ ID NO;
5, and wherein the amino acid Cys may be in the oxidized state forming S--S-bridges.
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Abstract
The invention concerns recombinant antibodies directed to the extracellular domain of the human growth factor receptor c-erbB-2 comprising a light chain variable domain and a heavy chain variable domain of a monoclonal antibody, monoclonal antibodies directed to c-erbB-2 themselves, a method of manufacturing those recombinant and monoclonal antibodies, hybridoma cells secreting those monoclonal antibodies, a method of manufacturing those hybridoma cells, DNAs encoding the heavy and light chain variable domains and the recombinant antibody, a method of manufacturing that DNA, hybrid vectors suitable for the expression of that DNA, host cells transformed with that DNA, and processes of using those recombinant and monoclonal antibodies in the diagnosis and treatment of tumors.
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Citations
19 Claims
- 1. A recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the heavy chain variable domain comprises a polypeptide of the formula
- space="preserve" listing-type="equation">FR.sub.1 -CDR.sub.1H -FR.sub.2 -CDR.sub.2H -FR.sub.3 -CDR.sub.3H -FR.sub.4 (I)
wherein FR1 is a polypeptide comprising 25-33 naturally occurring amino acids, FR2 is a polypeptide comprising 12-16 naturally occurring amino acids, FR3 is a polypeptide comprising 30-34 naturally occurring amino acids, FR4 is a polypeptide comprising 6-13 naturally occurring amino acids, CDR1H is a polypeptide of the amino acid sequence 32-36 of SEQ ID NO;
5, CDR2H is a polypeptide of the amino acid sequence 51-67 of SEQ ID NO;
5, CDR3H is a polypeptide of the amino acid sequence 100 to 109 of SEQ ID NO;
5, and wherein the amino acid Cys may be in the oxidized state forming S--S-bridges.- View Dependent Claims (2, 3)
- 4. A recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the light chain variable domain comprises a polypeptide of the formula
- space="preserve" listing-type="equation">FR.sub.6 -CDR.sub.1L -FR.sub.7 -CDR.sub.2L -FR.sub.8 -CDR.sub.3L -FR.sub.9 (II)
wherein FR6 is a polypeptide comprising naturally occurring amino acids, FR7 is a polypeptide comprising 13-17 naturally occurring amino acids, FR8 is a polypeptide comprising 30-34 naturally occurring amino acids, FR9 is a polypeptide comprising naturally occurring amino acids, CDR1L is a polypeptide of the amino acid sequence 159 to 169 of SEQ ID NO;
5, CDR2L is a polypeptide of the amino acid sequence 185 to 191 of SEQ ID NO;
5, and CDR3L is a polypeptide of the amino acid sequence 224 to 232 of SEQ ID NO;
5, and wherein the amino acid Cys may be in the oxidized state forming S--S-bridges.- View Dependent Claims (5, 6)
- 7. A recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the heavy chain variable domain comprises a polypeptide of the formula
- space="preserve" listing-type="equation">FR.sub.1 -CDR.sub.1H -FR.sub.2 -CDR.sub.2H -FR.sub.3 -CDR.sub.3H -FR.sub.4 (I)
wherein FR1 is a polypeptide comprising 25-33 naturally occurring amino acids, FR2 is a polypeptide comprising 12-16 naturally occurring amino acids, FR3 is a polypeptide comprising 30-34 naturally occurring amino acids, FR4 is a polypeptide comprising 6-13 naturally occurring amino acids, CDR1H is a polypeptide of the amino acid sequence 32 to 36 of SEQ ID NO;
11, CDR2H is a polypeptide of amino acid sequence 51 to 67 of SEQ ID NO;
11, and CDR3H is a polypeptide of the amino acid sequence 100 to 110 of SEQ ID NO;
11, and wherein the amino acid Cys may be in the oxidized state forming S--S-bridges.- View Dependent Claims (8, 9)
- 10. A recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the light chain variable domain comprises a polypeptide of the formula
- space="preserve" listing-type="equation">FR.sub.6 -CD.sub.1L -FR.sub.7 -CDR.sub.2L -FR.sub.8 -CDR.sub.3L -FR.sub.9 (II)
wherein FR6 is a polypeptide comprising naturally occurring amino acids, FR7 is a polypeptide comprising 13-17 naturally occurring amino acids, FR8 is a polypeptide comprising 30-34 naturally occurring amino acids, FR9 is a polypeptide comprising naturally occurring amino acids, CDR1L is a polypeptide of the amino acid sequence 160 to 170 of SEQ ID NO;
11, CDR2L is a polypeptide of the amino acid sequence 186 to 192 of SEQ ID NO;
11, and CDR3L is a polypeptide of the amino sequence 225 to 232 of SEQ ID NO;
11, and wherein the amino acid Cys may be in the oxidized state forming S--S-bridges.- View Dependent Claims (11, 12)
- 13. A single-chain recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the heavy chain variable domain and the light chain variable domain are linked by a polypeptide spacer group, and further wherein the heavy chain variable domain and the light chain variable domain are derived from the mouse monoclonal antibody FRP5.
- 17. A single-chain recombinant antibody directed to the extracellular domain of the growth factor receptor c-erbB-2 comprising of heavy chain variable domain and a light chain variable domain of a monoclonal antibody, wherein the heavy chain variable domain and the light chain variable domain are linked by a polypeptide spacer group, and further wherein the heavy chain variable domain and the light chain variable domain are derived from the mouse monoclonal antibody FWP51.
Specification