Hyperglycosylated binding polypeptides
Provided are binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof, comprising a CH1 domain (e.g., a human IgG1 CH1 domain), wherein the CH1 domain has an engineered N-linked glycosylation site at amino acid position 114, according to Kabat numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.
1. An isolated polynucleotide encoding a binding polypeptide comprising a CH1 domain, or a variant thereof, wherein the CH1 domain or the variant thereof comprises an asparagine residue at amino acid position 114, according to Kabat numbering.
2. A vector comprising the polynucleotide of claim 1 .
3. A host cell comprising the polynucleotide of claim 1 .
4. A method of making a binding polypeptide comprising expressing the polynucleotide of claim 1 in a cell.
5. An isolated host cell comprising the vector of claim 2 .
6. A method of making a binding polypeptide comprising expressing the vector of claim 2 in a cell.
7. The isolated polynucleotide of claim 1 , wherein the binding polypeptide is an antibody, or an antigen-binding fragment thereof.
8. The isolated polynucleotide of claim 1 , wherein the CH1 domain is an IgG1 CH1 domain.
9. The isolated polynucleotide of claim 8 , wherein the CH1 domain is a human IgG1 CH1 domain.
10. An isolated polynucleotide encoding a binding polypeptide comprising a CH1 domain, or a variant thereof, wherein the CH1 domain or the variant thereof comprises: an asparagine residue at amino acid position 114, according to Kabat numbering; any amino acid residue except proline at position 115, according to Kabat numbering; and a serine or threonine residue at position 116, according to Kabat numbering.
11. A vector comprising the polynucleotide of claim 10 .
12. An isolated host cell comprising the polynucleotide of claim 10 .
13. A method of making a binding polypeptide comprising expressing the polynucleotide of claim 10 in a cell.
14. An isolated host cell comprising the vector of claim 11 .
15. A method of making a binding polypeptide comprising expressing the vector of claim 11 in a cell.
16. The isolated polynucleotide of claim 10 , wherein the binding polypeptide is an antibody, or an antigen-binding fragment thereof.
17. The isolated polynucleotide of claim 10 , wherein the binding polypeptide is an antibody, or an antigen-binding fragment thereof.
18. The isolated polynucleotide of claim 10 , wherein the CH1 domain is an IgG1 CH1 domain.
19. The isolated polynucleotide of claim 18 , wherein the CH1 domain is a human IgG1 CH1 domain.