Monoclonal antibodies against Glypican-3
View Patent ↗The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to Glypican-3 with high affinity. Nucleic acid molecules encoding Glypican-3 antibodies, expression vectors, host cells and methods for expressing the Glypican-3 antibodies are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the Glypican-3 antibodies are also provided. Methods for detecting Glypican-3, as well as methods for treating various Glypican-3-related conditions, including hepatocellular cancer, are disclosed.
1. An isolated nucleic acid molecule encoding;
(a) a heavy chain of an anti-Glypican-3 antibody, or antigen-binding portion thereof, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 19; or
(b) a light chain of an anti-Glypican-3 antibody, or antigen-binding portion thereof, wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 22.
2. The nucleic acid molecule of claim 1 , comprising the nucleotide sequence of SEQ ID NO: 25.
3. The nucleic acid molecule of claim 1 , comprising the nucleotide sequence of SEQ ID NO: 28.
4. The nucleic acid molecule of claim 1 , encoding a heavy chain and a light chain of an anti-Glypican-3 antibody, or antigen-binding portion thereof, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 19 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 22.
5. An expression vector comprising the nucleic acid molecule of claim 1 .
6. A host cell comprising the expression vector of claim 5 .
7. A method for preparing an anti-Glypican-3 antibody, which comprises:
(a) obtaining a host cell that contains a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 19 and a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 22;
(b) growing the host cell in a host cell culture;
(c) providing host cell culture conditions wherein the nucleic acid molecules are expressed; and
(d) recovering the antibody from the host cell or from the host cell culture.
8. A method according to claim 7 , wherein the nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 19 and the nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 22 are inserted into separate expression vectors.
9. A method according to claim 7 , wherein the nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 19 and the nucleic acid molecule encoding the amino acid sequence of SEQ ID NO: 22 are inserted into the same expression vector.