Bispecific fusion antibodies with enhanced serum half-life
AssigneeDomantis Limited
InventorsLucy J. Holt, Ian M. Tomlinson
Life of this patent
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Abstract
Drug compositions, fusions and conjugates are provided. The drug fusions and conjugates contain a therapeutic or diagnostic agent that is fused or conjugated to an antigen-binding fragment of an antibody that binds serum albumin. The drug compositions, fusions and conjugates have a longer in vivo half-life in comparison with the unconjugated or unfused therapeutic or diagnostic agent.
Claims38
A drug fusion comprising moieties X′ and Y′, wherein
- X′ is a polypeptide drug, with the proviso that X′ does not comprise an antibody chain or a fragment of an antibody chain;
- and
- Y′ is an immunoglobulin single variable domain that has binding specificity for serum albumin, wherein Y′ is an amino acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23;
- and
- wherein said drug fusion has a longer in vivo serum half-life relative to said polypeptide drug.
A drug fusion comprising moieties X′ and Y′, wherein
- X′ is a polypeptide drug, with the proviso that X′ does not comprise an antibody chain or a fragment of an antibody chain;
- and
- Y′ is an immunoglobulin light chain single variable domain that has binding specificity for serum albumin;
- and
- wherein Y′ comprises the amino acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26.
A drug fusion comprising moieties X′ and Y′, wherein
- X′ is a polypeptide drug, with the proviso that X′ does not comprise an antibody chain or a fragment of an antibody chain;
- and
- Y′ is an immunoglobulin heavy chain single variable domain that has binding specificity for serum albumin;
- and
- wherein Y′ comprises the amino acid sequence selected from the group consisting of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23.
A drug conjugate comprising an immunoglobulin heavy chain single variable domain that has binding specificity for serum albumin, or an immunoglobulin light chain single variable domain that has binding specificity for serum albumin, and a drug that is covalently bonded to said immunoglobulin heavy chain single variable domain or said immunoglobulin light chain single variable domain, with the proviso that said drug does not comprise an antibody chain or a fragment of an antibody chain,
- wherein said immunoglobulin heavy chain single variable domain that has binding specificity for serum albumin, or said immunoglobulin light chain single variable domain that has binding specificity for serum albumin comprises an amino acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, and
- wherein said drug conjugate has a longer in vivo serum half-life relative to said drug.
A drug conjugate comprising an immunoglobulin heavy chain single variable domain that has binding specificity for serum albumin, or an immunoglobulin light chain single variable domain that has binding specificity for serum albumin, and a drug that is covalently bonded to said immunoglobulin heavy chain single variable domain or said immunoglobulin light chain single variable domain, with the proviso that said drug does not comprise an antibody chain or a fragment of an antibody chain;
- wherein said immunoglobulin heavy chain single variable domain that has binding specificity for serum albumin, or said immunoglobulin light chain single variable domain that has binding specificity for serum albumin comprises an amino acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23.
A noncovalent drug conjugate comprising an immunoglobulin single variable domain that has binding specificity for serum albumin, and a drug that is noncovalently bonded to said immunoglobulin single variable domain, wherein said immunoglobulin single variable domain is selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23,
- with the proviso that said drug does not comprise an antibody chain or a fragment of an antibody chain, and wherein said noncovalent drug conjugate has a longer in vivo serum half-life relative to said drug.
A method for increasing the in vivo serum half-life of a drug without substantially reducing the activity of the drug, comprising binding a drug to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, whereby a drug composition is produced,
- wherein said drug composition has a longer in vivo serum half-life relative to said drug.
A method for increasing the in vivo serum half-life of a drug and reducing the immunogenicity of the drug, comprising binding a drug to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, whereby a drug composition is produced,
- wherein said drug composition has a longer in vivo serum half-life relative to said drug, and is less immunogenic than said drug.
A method for decreasing the immunogenicity of a drug without substantially reducing the activity of the drug, comprising binding a drug to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, whereby a drug composition is produced,
- wherein said drug composition is less immunogenic than said drug.
A method for increasing the in vivo serum half-life of a drug and reducing the immunogenicity of the drug without substantially reducing the activity of the drug, comprising binding a drug to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23, whereby a drug composition is produced,
- wherein said drug and composition has a longer in vivo serum half-life relative to said drug, is less immunogenic than said drug.
A drug composition comprising a drug that is bound to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23,
- wherein said drug composition has a longer in vivo serum half-life relative to drug.
A drug composition comprising a drug that is bound to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23,
- wherein said drug composition has a longer in vivo serum half-life relative to said drug, and is less immunogenic than said drug.
A drug composition comprising a drug that is bound to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23,
- wherein said drug composition is less immunogenic than said drug.
A drug composition comprising a drug that is bound to a polypeptide binding moiety selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23,
- wherein said drug composition has a longer in vivo serum half-life relative to said drug, is less immunogenic than said drug.
Dependencies are inferred from the claim text.