HUMAN MONOCLONAL ANTIBODIES TO GANGLIOSIDE GD2
The present invention provides compositions for the production of an antibody or functional fragment thereof directed against disialoganglioside-GD2. The compositions of the invention include polynucleotides encoding a heavy chain and/or a light chain variable domain that binds to GD2. The invention also provides an isolated antibody or functional fragment thereof and methods of treating or preventing a disease, such as cancer or tumor formation, wherein the antibody or functional fragment includes a variable heavy chain domain and a variable light chain domain that has an amino acid sequence provided herein. The invention further provides a conjugate of an antibody or functional fragment thereof conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent, and methods of treating, preventing or diagnosing a disease in a subject in need thereof.
1 - 31 . (canceled)
32 . An isolated polynucleotide comprising a nucleotide sequence encoding an antibody heavy chain,
wherein said antibody heavy chain has VH CDR1, VH CDR2, and VH CDR3 amino acid sequences that comprise residues 26-33, residues 51-58, and residues 97-110 of SEQ ID NO: 34, respectively, or
wherein said antibody heavy chain has VH CDR1, VH CDR2, and VH CDR3 amino acid sequences that comprise residues 26-33, residues 51-58, and residues 97-110 of SEQ ID NO: 36, respectively.
33 . The isolated polynucleotide of claim 32 , wherein said antibody heavy chain comprises the variable heavy chain (VH) domain comprising the amino acid sequence of SEQ ID NO: 34 or 36.
34 . The isolated polynucleotide of claim 33 , comprising the nucleotide sequence of SEQ ID NO: 33 or 35.
35 . The isolated polynucleotide of claim 34 , further comprising the nucleotide sequence of SEQ ID NO: 37.
36 . An isolated polynucleotide comprising a nucleotide sequence encoding an antibody light chain, wherein said antibody light chain has VL CDR1, VL CDR2, and VL CDR3 amino acid sequences that comprise residues 27-32, residues 50-52, and residues 89-97 of SEQ ID NO: 38, respectively.
37 . The isolated polynucleotide of claim 36 , wherein the antibody light chain comprises a variable light chain (VL) domain comprising the amino acid sequence of SEQ ID NO: 38.
38 . The isolated polynucleotide of claim 37 , comprising the nucleotide sequence of SEQ ID NO: 37.
39 . An isolated antibody heavy chain comprising a variable heavy chain (VH) domain, wherein said VH domain comprises the amino acid sequence of SEQ ID NO: 34 or wherein said VH domain comprises the amino acid sequence of SEQ ID NO: 36.
40 . An isolated antibody light chain comprising a variable light chain (VL) domain, wherein said VL domain comprises the amino acid sequence of SEQ ID NO: 38.
41 . An isolated antibody or antigen binding fragment thereof that binds to GD2, said antibody or antigen binding fragment thereof comprising a variable heavy chain (VH) domain and a variable light chain (VL) domain;
wherein said VH domain comprises VH CDR1, VH CDR2, and VH CDR3 amino acid sequences that comprise residues 26-33, residues 51-58, and residues 97-110 of SEQ ID NO: 34, respectively, or wherein said VH domain comprises VH CDR1, VH CDR2, and VH CDR3 amino acid sequences that comprise residues 26-33, residues 51-58, and residues 97-110 of SEQ ID NO: 36, respectively; and
wherein said VL domain comprises VL CDR1, VL CDR2, and VL CDR3 amino acid sequences that comprise residues 27-32, residues 50-52, and residues 89-97 of SEQ ID NO: 38, respectively.
42 . The isolated antibody or antigen binding fragment thereof of claim 41 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 34 or 36; and
wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 38.
43 . The isolated antibody or antigen binding fragment thereof of claim 41 , wherein said antibody is a human antibody.
44 . The isolated antibody or antigen binding fragment thereof of claim 41 , wherein said antibody or antigen binding fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, a scFV, a diabody, a triabody, and a minibody.
45 . The isolated antibody or antigen binding fragment thereof of claim 41 , wherein said antibody is a monoclonal antibody.
46 . The isolated antibody or antigen binding fragment thereof of claim 41 , wherein said antibody is an IgG or IgM isotope.
47 . The isolated antibody or antigen binding fragment thereof of claim 46 , wherein said IgG antibody is an IgG1 subclass.
48 . A conjugate comprising the isolated antibody or antigen binding fragment thereof of claim 41 conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent.
49 . The conjugate of claim 48 , wherein said antibody or antigen binding fragment thereof is conjugated or recombinantly fused to a detectable agent.
50 . A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 41 and a pharmaceutically acceptable carrier.