Antibody with non-natural amino acid introduced therein
The present invention relates to a monoclonal antibody or antibody fragment thereof as a human IgG antibody including at least one lysine derivative in a constant region of the human IgG antibody; a modified antibody or antibody fragment thereof, wherein the lysine derivative is modified; a nucleic acid including a nucleotide sequence encoding the antibody or antibody fragment thereof; a vector including the nucleic acid; a transformed cell obtained by introducing the vector into a host cell; a method for producing the antibody or antibody fragment thereof; and a composition containing the antibody or antibody fragment thereof.
1. A monoclonal IgG antibody or antigen-binding fragment thereof, wherein in said monoclonal antibody or antigen-binding fragment thereof, at least one amino acid residue selected from the group consisting of amino acid residues at positions 131, 177, and 199 of a heavy chain of a human IgG antibody and amino acid residues at positions 155, 191, and 197 of a κ chain of a human antibody according to the EU-index numbering is a Z-lysine derivative.
2. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein at least one Z-lysine derivative is modified.
3. The monoclonal antibody or antigen-binding fragment thereof according to claim 2 , wherein the modification is chemical modification with a molecule having reactivity with a Z-lysine derivative.
4. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the molecule having reactivity with a Z-lysine derivative is at least one molecule selected from the group consisting of hydrophilic polymer, amphiphilic polymer, and a functional molecule.
5. The monoclonal antibody or antigen-binding fragment thereof according to claim 3 , wherein the molecule having reactivity with a Z-lysine derivative is at least one molecule selected from the group consisting of PEG, an antigen-binding molecule, a drug, and a fluorescent compound.
6. The monoclonal antibody or antigen-binding fragment thereof according to claim 5 , wherein the antigen-binding molecule is a monoclonal antibody or an antigen-binding fragment thereof.
7. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment is selected from the group consisting of an Fab, an Fab′, and an (Fab′) 2 .
8. The monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the monoclonal antibody is a recombinant antibody.
9. The monoclonal antibody or antigen-binding fragment thereof according to claim 8 , wherein the recombinant antibody is a chimeric antibody, a humanized antibody, or a human antibody.
10. A composition comprising the monoclonal antibody or antigen-binding fragment thereof according to claim 1 .
11. A monoclonal IgG antibody or antigen-binding fragment thereof comprising at least one lysine derivative selected from the group consisting of N6-(((trans-cyclooct-2-en-1-yl)oxy)carbonyl)-L-lysine (hereinafter, abbreviated as “TCO*-Lys”) and N6-((bicyclo[6.1.0]non-4-yn-9-ylmethoxy)carbonyl)-L-lysine (hereinafter, abbreviated as “BCN-Lys”) in a constant region of the antibody or antigen-binding fragment thereof,
wherein in said monoclonal antibody or antigen-binding fragment thereof, at least one amino acid residue selected from the group consisting of amino acid residues at positions 131, 177, and 199 of a heavy chain of a human IgG antibody and amino acid residues at positions 155, 191, and 197 of a κ chain of a human antibody according to the EU-index numbering is a lysine derivative.
12. The monoclonal antibody or antigen-binding fragment thereof according to claim 11 , wherein at least one lysine derivative is modified.
13. The monoclonal antibody or antigen-binding fragment thereof according to claim 12 , wherein the modification is chemical modification with a molecule having reactivity with a lysine derivative.
14. The monoclonal antibody or antigen-binding fragment thereof according to claim 13 , wherein the molecule having reactivity with a lysine derivative is at least one molecule selected from the group consisting of hydrophilic polymer, amphiphilic polymer, and functional molecule.
15. The monoclonal antibody or antigen-binding fragment thereof according to claim 13 , wherein the molecule having reactivity with a lysine derivative is at least one molecule selected from the group consisting of PEG, an antigen-binding molecule, a drug, and a fluorescent compound.
16. The monoclonal antibody or antigen-binding fragment thereof according to claim 15 , wherein the antigen-binding molecule is a monoclonal antibody or an antigen-binding fragment thereof.
17. The monoclonal antibody or antigen-binding fragment thereof according to claim 11 , wherein the antigen-binding fragment is selected from the group consisting of an Fab, an Fab′, and an (Fab′) 2 .
18. The monoclonal antibody or antigen-binding fragment thereof according to claim 11 , wherein the monoclonal antibody is a recombinant antibody.
19. The monoclonal antibody or antigen-binding fragment thereof according to claim 18 , wherein the recombinant antibody is a chimeric antibody, a humanized antibody, or a human antibody.
20. A composition comprising the monoclonal antibody or antigen-binding fragment thereof according to claim 11 .