Methods of using monoclonal antibodies targeting epitopes of ASPH
AssigneeMidwestern University
InventorMark Jon Olsen
Life of this patent
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Abstract
Monoclonal antibodies (MAbs) targeting one or more specific epitopes of aspartyl (asparaginyl) β-hydroxylase (ASPH), including humanized, bi-specific, and other chimeric MAb variants, and fragments thereof (collectively ASPH epitope-specific MAbs, or simply ASPH MAbs), are disclosed. Methods of production, purification, and use of the ASPH epitope-specific MAbs, and compositions comprising them, as agents in therapeutic and diagnostic applications to interact with target molecules in cell-free samples, cell- and tissue-based assays, animal models, and in a subject are also disclosed. Other aspects of the invention relate to use of the molecules disclosed herein to diagnose, ameliorate, or treat cell proliferation disorders and related diseases.
Claims13
A method of treating cancer in a mammalian subject, comprising administering to a subject in need thereof a composition comprising an antibody or fragment or variant thereof, which binds to one or more peptide epitopes of human aspartyl (asparaginyl) β-hydroxylase (ASPH) in an amount sufficient to treat cancer, wherein said antibody comprises:
- a recombinant heavy chain and a recombinant light chain, each heavy and each light chain comprising 3 complementarity-determining regions (CDRs), or fragment or variant thereof, which binds to one or more peptide epitopes of human aspartyl (asparaginyl) β-hydroxylase (ASPH), wherein at least one of said peptide epitopes comprises at least 4 consecutive amino acid residues located within or adjacent to a position in the catalytic domain of ASPH that is within 30 amino acids of the C-terminus of human ASPH, corresponding to the sequence
- QDASSFRLIFIVDVWHPELTPQQRRSLPAI represented by positions 729-758 of SEQ ID NO:
- 1;
- wherein said antibody or fragment or variant thereof contains one or more conservative amino acid substitutions in which the functional activity relating to binding of the antibody or fragment thereof to an epitope of ASPH is retained;
- wherein said antibody comprises a recombinant heavy chain comprising
- a CDR1 comprising a sequence selected from the group consisting of
- NFMC represented by SEQ ID NO:
- 31, and
- NAMC represented by SEQ ID NO:
- 32;
- a CDR2 comprising a sequence selected from the group consisting of
- CIYF represented by SEQ ID NO:
- 33, and
- CIDN represented by SEQ ID NO:
- 34;
- and
- a CDR3 comprising a sequence selected from the group consisting of
- DGPGSISWKI represented by SEQ ID NO:
- 35, and
- NFNI represented by SEQ ID NO:
- 36;
- wherein said antibody comprises a recombinant light chain comprising
- a CDR1 comprising a sequence selected from the group consisting of
- SVYSKNR represented by SEQ ID NO:
- 37, and
- SVYDNNR represented by SEQ ID NO:
- 38;
- a CDR2 comprising the sequence
- LAS represented by SEQ ID NO:
- 39;
- and
- a CDR3 comprising a sequence selected from the group consisting of
- QGTYDSSGWYWA represented by SEQ ID NO:
- 40, and
- LGSYSGYIYI represented by SEQ ID NO:
- 41.
A method of treating cancer in a mammalian subject comprising administering to a subject in need thereof a composition comprising a monoclonal antibody comprising a recombinant heavy chain and a recombinant light chain, or a fragment thereof, which binds to one or more peptide epitopes of human aspartyl (asparaginyl) β-hydroxylase (ASPH), wherein at least one of said peptide epitopes is located within or adjacent to a position in the catalytic domain of ASPH that is within 30 amino acids of the C-terminus of human ASPH, corresponding to the sequence
- QDASSFRLIFIVDVWHPELTPQQRRSLPAI represented by positions 729-758 of SEQ ID NO:
- 1;
- wherein said antibody binds to an epitope comprising at least 4 consecutive amino acid residues located within 30 amino acids from the C-terminal end of human ASPH represented by SEQ ID NO:
- 1;
- wherein said antibody comprises a recombinant heavy chain and a recombinant light chain,
- wherein said recombinant heavy chain comprises
- a polypeptide sequence selected from the group consisting of SEQ ID NOS 21-25;
- and
- wherein said recombinant light chain comprises
- a polypeptide sequence selected from the group consisting of SEQ ID NOS 26-30.
A method of inhibiting the proliferation of tumor cell or tissue samples grown in culture, comprising administering to the locus of the tumor cells a composition comprising an antibody or fragment or variant thereof which binds to one or more peptide epitopes of human aspartyl (asparaginyl) β-hydroxylase (ASPH) in an amount sufficient to inhibit proliferation, wherein said antibody comprises
- a recombinant heavy chain and a recombinant light chain, each heavy and each light chain comprising 3 complementarity-determining regions (CDRs), or fragment or variant thereof, which binds to one or more peptide epitopes of human aspartyl (asparaginyl) β-hydroxylase (ASPH), wherein at least one of said peptide epitopes comprises at least 4 consecutive amino acid residues located within or adjacent to a position in the catalytic domain of ASPH that is within 30 amino acids of the C-terminus of human ASPH, corresponding to the sequence
- QDASSFRLIFIVDVWHPELTPQQRRSLPAI represented by positions 729-758 of SEQ ID NO:
- 1;
- wherein said antibody or fragment or variant thereof contains one or more conservative amino acid substitutions in which the functional activity relating to binding of the antibody or fragment thereof to an epitope of ASPH is retained;
- wherein said antibody comprises a recombinant heavy chain comprising
- a CDR1 comprising a sequence selected from the group consisting of
- NFMC represented by SEQ ID NO:
- 31, and
- NAMC represented by SEQ ID NO:
- 32;
- a CDR2 comprising a sequence selected from the group consisting of
- CIYF represented by SEQ ID NO:
- 33, and
- CIDN represented by SEQ ID NO:
- 34;
- and
- a CDR3 comprising a sequence selected from the group consisting of
- DGPGSISWKI represented by SEQ ID NO:
- 35, and
- NFNI represented by SEQ ID NO:
- 36;
- wherein said antibody comprises a recombinant light chain comprising
- a CDR1 comprising a sequence selected from the group consisting of
- SVYSKNR represented by SEQ ID NO:
- 37, and
- SVYDNNR represented by SEQ ID NO:
- 38;
- a CDR2 comprising the sequence
- LAS represented by SEQ ID NO:
- 39;
- and
- a CDR3 comprising a sequence selected from the group consisting of
- QGTYDSSGWYWA represented by SEQ ID NO:
- 40, and
- LGSYSGYIYI represented by SEQ ID NO:
- 41.
Dependencies are inferred from the claim text.