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US 12,649,791 B2Granted
IgM Fc and j-chain mutations that affect IgM serum half-life
AssigneeIGM Biosciences, Inc.
InventorsRamesh Baliga, Bruce Keyt, Dean Ng
Life of this patent
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Abstract
This disclosure provides an IgM antibody or IgM-like antibody comprising a variant J-chain and/or variant IgM heavy chain constant regions that can confer increased serum half-life upon the antibody.
Claims26
A polynucleotide encoding an IgM antibody with enhanced serum half-life comprising:
- a nucleic acid encoding an IgM heavy chain that comprises an IgM heavy chain constant region fused to a single chain Fv (scFv), a single domain variable region (VHH), or a heavy chain variable region (VH),
- a nucleic acid encoding an antibody light chain that comprises a human antibody light chain constant region fused to a light chain variable region (VL), and
- a nucleic acid encoding a variant J chain that comprises the amino acid sequence of SEQ ID NO:
- 2 except for:
- an alanine (A), serine(S), or arginine (R) substitution at amino acid Y102 of SEQ ID NO:
- 2, an alanine (A) substitution at amino acid T103 of SEQ ID NO:
- 2, an alanine (A) substitution at amino acid N49 of SEQ ID NO:
- 2, or a combination thereof;
- wherein the IgM antibody encoded by the polynucleotide exhibits an increased serum half-life upon administration to a subject animal relative to a reference IgM antibody that is identical except that the J chain comprises SEQ ID NO:
- 2, and wherein the IgM antibody and the reference IgM antibody are administered in the same way to the same animal species.
7 more elements
A polynucleotide encoding an IgM antibody with enhanced serum half-life comprising:
- a nucleic acid encoding a variant IgM heavy chain that comprises an IgM heavy chain constant region fused to a single chain Fv (scFv), a single domain variable region (VHH), or a heavy chain variable region (VH), wherein the variant IgM heavy chain constant region is identical to a human IgM heavy chain constant region except for:
- an alanine (A) substitution at a position corresponding to amino acid S401 of SEQ ID NO:
- 12, an alanine (A) substitution at a position corresponding to amino acid E402 of SEQ ID NO:
- 12, or alanine (A) substitutions at positions corresponding to amino acids S401 and E402 of SEQ ID NO:
- 12;
- and
- a nucleic acid encoding an antibody light chain comprising a human antibody light chain constant region fused to a light chain variable region (VL);
- wherein the IgM antibody encoded by the polynucleotide exhibits an increased serum half-life upon administration to a subject animal relative to a reference IgM antibody that is identical except that the IgM heavy chain constant region comprises SEQ ID NO:
- 12, and wherein the IgM antibody and the reference IgM antibody are administered in the same way to the same animal species.
6 more elements
Dependencies are inferred from the claim text.