Multimers, tetramers and octamers
AssigneeQuadrucept Bio Limited
InventorsHanif Ali, Terence Rabbitts, Christian Grøndahl, Jasper Clube
Life of this patent
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Abstract
The invention relates to multimers such as tetramers of polypeptides and tetramers and octamers of effector domains, such as antigen binding sites (eg, antibody or TCR binding sites that specifically bind to antigen or pMHC, or variable domains thereof) or peptides such as incretin, insulin or hormone peptides.
Claims25
A protein multimer of at least first, second, third and fourth copies of an effector domain or a peptide, wherein the multimer is multimerized by first, second, third and fourth self-associating tetramerization domains (TDs) which are associated together, wherein each tetramerization domain is comprised by a respective engineered polypeptide comprising one or more copies of said effector domain or peptide,
- wherein
- (i) each TD is a p53 TD or a homologue or orthologue thereof;
- (ii) the multimer is soluble in an aqueous medium and is obtainable by extracellular secretion from a eukaryotic cell;
- and
- (iii) wherein the multimer comprises eukaryotic cell glycosylation.
A tetramer or octamer of
- (a) TCR V domains or TCR binding sites, wherein the tetramer or octamer is soluble in aqueous solution;
- (b) antibody single variable domains, wherein the tetramer or octamer is soluble in aqueous solution;
- (c) TCR V domains or TCR binding sites, wherein the tetramer or octamer is capable of being extracellularly expressed by HEK293 cells;
- or
- (d) antibody variable domains, wherein the tetramer or octamer is capable of being extracellularly expressed by HEK293 cells,
- wherein the tetramer or octamer comprises eukaryotic cell glycosylation.
A protein multimer of at least first, second, third and fourth copies of an effector domain or a peptide, wherein the multimer is multimerized by first, second, third and fourth self-associating tetramerization domains (TDs) which are associated together, wherein each tetramerization domain is comprised by a respective engineered polypeptide comprising one or more copies of said effector domain or peptide,
- wherein
- (i) each TD is a p53 TD or a homologue or orthologue thereof;
- (ii) the multimer is soluble in an aqueous medium and is obtainable by extracellular secretion from a eukaryotic cell;
- and
- (iii) wherein each engineered polypeptide comprises first and second copies of said effector domain or peptide, wherein each engineered polypeptide comprises in N- to C-terminal direction (i) a first of said copies—TD—the second of said copies;
- (ii) TD—the first and second copies;
- or (iii) said first and second copies—TD.
An engineered polypeptide, wherein the engineered polypeptide comprises one or more copies of an effector domain or peptide and a self-associating tetramerization domain (TD),
- wherein the TD is capable of multimerizing to form a protein multimer of at least first, second, third and fourth copies of the effector domain or peptide,
- wherein the TD is a p53 TD or a homologue or orthologue thereof, and
- (i) each TD of the multimer is a p53 TD or a homologue or orthologue thereof;
- and
- (ii) the multimer is soluble in an aqueous medium and is obtainable by extracellular secretion of the engineered polypeptide from a eukaryotic cell, and the engineered polypeptide comprises in N- to C-terminal direction:
- (a) antibody V1—antibody CH1—optional linker—TD, wherein
- (i) V1 is a VH;
- or
- (ii) V1 is a VL;
- or
- (b) antibody V1—optional antibody CH1—antibody Fc—optional linker—TD, wherein
- (i) V1 is a VH;
- or
- (ii) V1 is a VL;
- or
- (c) antibody V1—antibody CL—optional linker—TD, wherein
- (i) V1 is a VH;
- or
- (i) V1 is a VL.
Dependencies are inferred from the claim text.