Human monoclonal antibodies against CD30
AssigneeMedarex, Inc.
InventorsTibor Keler, Robert Graziano, John Treml, Yashwant M. Deo
Life of this patent
Estimating the term…
Abstract
Isolated human monoclonal antibodies which bind to CD30 (e.g., human CD30) are disclosed. The human antibodies can be produced in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are derivatives of the human antibodies (e.g., bispecific antibodies and immunoconjugates), pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.
Claims48
An isolated human monoclonal antibody which binds to human CD30.
An isolated human monoclonal antibody comprising a human heavy chain variable region comprising FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 sequences and a human light chain variable region comprising FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 sequences, wherein:
- (a) the human heavy chain variable region CDR3 sequence is selected from the group consisting of SEQ ID NOs:
- 18, 30 and 42, and conservative modifications thereof;
- (b) the human light chain variable region CDR3 sequence is selected from the group consisting of SEQ ID NOs:
- 24, 36 and 48, and conservative modifications thereof;
- (c) the human antibody binds to human CD30 with an affinity constant of at least 107 M−1;
- (d) the human antibody mediates lysis of CD30+ tumor cells in an antibody dependent cellular cytotoxicity (ADCC) assay;
- and
- (e) the human antibody inhibits growth of CD30+ tumor cells in vivo.
An isolated human monoclonal antibody comprising a human heavy chain variable region and a human light chain variable region, wherein:
- (a) the human heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 6, 10, and sequences that are at least 80% homologous to SEQ ID NOs:
- 2, 6 and 10;
- (b) the human light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 4, 8, 12, and sequences that are at least 80% homologous to SEQ ID NOs:
- 4, 8 and 12;
- (c) the human antibody binds to human CD30 with an affinity constant of at least 107 M−1;
- (d) the human antibody mediates lysis of CD30+ tumor cells in an antibody dependent cellular cytotoxicity (ADCC) assay;
- and
- (e) the human antibody inhibits growth of CD30+ tumor cells in vivo.
An isolated human monoclonal antibody comprising a human heavy chain variable region derived from the human heavy chain VH4-34 germline sequence and a human light chain variable region derived from the human light chain L15 germline sequence, wherein:
- (a) the human heavy chain variable region comprises the amino acid sequence of SEQ ID NO:
- 10 or a sequence that is at least 80% homologous to SEQ ID NO:
- 10;
- (b) the human light chain variable region comprises the amino acid sequence of SEQ ID NO:
- 12 or a sequences that is at least 80% homologous to SEQ ID NO:
- 12;
- (c) the human antibody binds to human CD30 with an affinity constant of at least 107 M−1;
- (d) the human antibody mediates lysis of CD30+ tumor cells in an antibody dependent cellular cytotoxicity (ADCC) assay;
- and
- (e) the human antibody inhibits growth of CD30+ tumor cells in vivo.
An isolated human monoclonal antibody comprising human heavy chain and human light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:2 and SEQ ID NO:4, respectively.
An isolated human monoclonal antibody comprising human heavy chain and human light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:
- 6 and SEQ ID NO:8, respectively.
An isolated human monoclonal antibody comprising human heavy chain and human light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:
- 10 and SEQ ID NO:12, respectively.
Dependencies are inferred from the claim text.