High affinity human antibodies to tumor antigens
AssigneeThe Regents of the University of California
InventorsJames D. Marks, Robert Schier
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Abstract
This invention provides novel human antibodies that specifically bind to human c-erbB-2. In one embodiment, the antibodies are single chain antibodies initially developed by phage display against a c-erbB-2 target. The resulting antibodies (designated C6 antibodies) show improved specificity and affinity for c-erbB-2. In addition, since the C6 antibodies are both relatively small and fully human they are less immunogenic in humans than other (e.g., full-size or chimeric) anti-c-erbB-2 antibodies. The C6 antibodies may be used alone or as components of chimeric molecules that specifically target and deliver effector molecules to cells overexpressing c-erbB-2.
Claims40
An isolated human antibody that specifically binds to c-erbB-2, said antibody being a C6 antibody, wherein said C6 antibody has the variable heavy (V.sub.H) chain of C6.5 (SEQ ID NO. 32) or the variable light (V.sub.L) chain of C6.5 (SEO ID NO. 36).
A polypeptide comprising one or more of the complementarity determining regions (CDRs) whose amino acid sequence contains a CDR sequence selected from the group consisting of the CDRs listed in Tables 4 (SEQ ID NOs. 6-24), 10 (SEQ ID NOs. 36 and 39-43), 12 (SEQ ID NOs. 44-59), 14 (SEQ ID NOs. 61 and 68-95), and 15 (SEQ ID NOs. 6, 7, 9, 12, 14, 15, 20-24, and 97-109).
An antibody selected from the group consisting of an antibody having a V.sub.L domain with one of the amino acid sequences shown in Table 10, (SEQ ID NOs. 36 and 39-43) an antibody having a V.sub.H domain with one of the amino acid sequences shown in Table 12 (SEQ ID NOs. 44-59), an antibody having a V.sub.L CDR3 domain having one of the amino acid sequences shown in Tables 4 (SEQ ID NOs. 6-24) and 15 (SEQ ID NOs. 6, 7, 9, 12, 14, 15, 20-24, and 97-109), and an antibody having a V.sub.H CDR3 domain having one of the amino acid sequences shown in Table 14 (SEQ ID NOs. 61 and 68-95).
An isolated human antibody that specifically binds to c-erbB-2, said antibody being a C6 antibody, wherein said C6 antibody comprises a framework region of C6.5 (V.sub.H SEO ID NO. 32 linked to V.sub.L SEO ID NO.36).
An isolated human antibody that specifically binds to c-erbB-2, said antibody being a C6 antibody, wherein said C6 antibody comprises a C6.5 complementarity determining region (amino acids 31-35, 50-66, or 99-118 of SEQ ID NO. 32 or amino acids 23-35, 51-57, and 90-98 of SEQ ID NO. 36).
An isolated human single chain antibody that has a binding affinity (K.sub.d) of 1.times.10.sup.-9 or greater for a c-erbB-2 on an SK-BR-3 cell as determined by a Scatchard assay or for a purified c-erbB-2 as determined by surface plasmon resonance in a BIAcore.
Dependencies are inferred from the claim text.