Stabilized human IgG2 and IgG3 antibodies
View Patent ↗It is intended to provide highly stable variants of human antibody IgG2 and IgG3 subclasses. The present invention provides an IgG heavy chain comprising the constant region of a human IgG2 heavy chain having at least a substitution of Y for F at the 300th position, L for V at the 309th position, or A for T at the 339th position designated by the EU index of Kabat et al. and an IgG heavy chain comprising the constant region of a human IgG3 heavy chain having at least a substitution of K for N at the 392nd position or V for M at the 397th position designated by the EU index of Kabat et al. The present invention also provides monoclonal antibodies comprising these heavy chains.
1. An isolated and non-naturally occurring IgG heavy chain comprising the constant region of a human IgG2 heavy chain having at least a substitution of Y for F at the 300th position designated by the EU index as defined by Kabat.
2. An isolated and non-naturally occurring IgG heavy chain comprising the constant region of a human IgG2 heavy chain having at least a substitution of L for V at the 309th position designated by the EU index as defined by Kabat.
3. An isolated and non-naturally occurring IgG heavy chain comprising the constant region of a human IgG2 heavy chain having at least a substitution of A for T at the 339th position designated by the EU index as defined by Kabat.
4. A method for producing an IgG antibody, comprising the step of substituting Y for F at the 300th position designated by the EU index as defined by Kabat in the constant region of a human IgG2 heavy chain.
5. A method for producing an IgG heavy chain, comprising the step of substituting L for V at the 309th position designated by the EU index as defined by Kabat in the constant region of a human IgG2 heavy chain.
6. A method for producing an IgG antibody, comprising the step of substituting A for T at the 339th position designated by the EU index as defined by Kabat in the constant region of a human IgG2 heavy chain.
7. A method for producing a monoclonal antibody, comprising a production method according to any one of claims 4 to 6 .
8. A method for producing a monoclonal antibody, comprising the step of: culturing, in a culture solution, a host comprising an expression vector having polynucleotides encoding the heavy and light chains of the IgG antibody according to any one of claims 1 - 3 ; and obtaining a monoclonal antibody from the resulting cultures and/or the host.
9. A method for suppressing monoclonal antibody aggregation, characterized by comprising substituting Y for F at the 300th position designated by the EU index as defined by Kabat in the constant region of a human IgG2 heavy chain.
10. A method for suppressing monoclonal antibody aggregation, characterized by comprising substituting L for V at the 309th position designated by the EU index as defined by Kabat in the constant region of a human IgG2 heavy chain.
11. A method for suppressing monoclonal antibody aggregation, characterized by comprising substituting A for T at the 339th position designated by the EU index as defined by Kabat in the constant region of a human IgG2 heavy chain.
12. An isolated and non-naturally occurring IgG heavy chain comprising the constant region of a human IgG3 heavy chain having at least a substitution of V for M at the 397th position designated by the EU index as defined by Kabat.
13. A method for producing an IgG heavy chain, comprising the step of substituting K for N at the 392nd position designated by the EU index as defined by Kabat in the constant region of a human IgG3 heavy chain.
14. A method for producing an IgG antibody, comprising the step of substituting V for M at the 397th position designated by the EU index as defined by Kabat in the constant region of a human IgG3 heavy chain.
15. A method for producing a monoclonal antibody, comprising a production method according to claim 13 .
16. A method for producing a monoclonal antibody, comprising the step of: culturing, in a culture solution, a host comprising an expression vector having polynucleotides encoding the heavy and light chains of a monoclonal antibody according to claim 12 ; and obtaining a monoclonal antibody from the resulting cultures and/or the host.
17. A method for suppressing monoclonal antibody aggregation, characterized by comprising substituting K for N at the 392nd position designated by the EU index as defined by Kabat in the constant region of a human IgG3 heavy chain.
18. A method for suppressing monoclonal antibody aggregation, characterized by comprising substituting V for M at the 397th position designated by the EU index as defined by Kabat in the constant region of a human IgG3 heavy chain.
19. An antibody comprising the constant region of a human IgG3 heavy chain according to claim 12 , wherein the antibody is a monoclonal antibody.
20. A method for producing a monoclonal antibody, comprising a production method according to claim 14 .