Polypeptide variants with altered effector function
The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.
1. A polypeptide comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the variant Fc region comprises an amino acid substitution at position 307, wherein the numbering of the position in the variant Fc region is that of the EU index as in Kabat.
2. An antibody comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the variant Fc region comprises an amino acid substitution at position 307, wherein the numbering of the position in the variant Fc region is that of the EU index as in Kabat.
3. An immunoadhesin comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the variant Fc region comprises an amino acid substitution at position 307, wherein the numbering of the position in the variant Fc region is that of the EU index as in Kabat.
4. The polypeptide of claim 1 , wherein said variant human IgG Fc region is a variant human IgG1 Fc region.
5. The polypeptide of claim 1 or claim 4 comprising a T307A substitution.
6. The polypeptide of claim 1 or claim 4 comprising a T307Q substitution.
7. The polypeptide of claim 4 wherein the variant Fc region has increased human neonatal Fc receptor (FcRn) binding affinity compared to a native sequence human IgG1 Fc region.
8. An antibody comprising a variant human IgG1 Fc region which has increased neonatal Fc receptor (FcRn) binding affinity, wherein the variant human IgG1 Fc region comprises a T307A or T307Q substitution, wherein the numbering of the position of the substitution in the variant human IgG1 Fc region is that of the EU index as in Kabat.
9. The antibody of claim 8 , wherein the variant human IgG1 Fc region comprises a T307A substitution.
10. The antibody of claim 8 , wherein the variant human IgG1 Fc region comprises a T307Q substitution.
11. A composition comprising the polypeptide of claim 1 or claim 4 and a pharmaceutically acceptable carrier.
12. The composition of claim 11 which is sterile.
13. A composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier.
14. The composition of claim 13 which is sterile.
15. An isolated host cell comprising a nucleic acid encoding the polypeptide of claim 1 or claim 4 .
16. A method for producing a polypeptide comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased FcRn binding affinity, wherein the variant Fc region comprises an amino acid substitution at position 307, wherein the numbering of the position in the variant Fc region is that of the EU index as in Kabat, and wherein the method comprises culturing the host cell of claim 15 so that the polypeptide is expressed from the nucleic acid.
17. The method of claim 16 further comprising recovering the polypeptide from the host cell culture.
18. A composition comprising the antibody of claim 2 or the immunoadhesin of claim 3 , which composition is sterile.
19. The antibody of claim 2 , wherein the variant human IgG Fc region comprises a T307A or T307Q substitution, wherein the numbering of the position of the substitution in the variant human IgG Fc region is that of the EU index as in Kabat.
20. The antibody of claim 2 , wherein the variant human IgG Fc region is a variant human IgG1 Fc region and wherein the variant Fc region has increased human neonatal Fc receptor (FcRn) binding affinity compared to a native sequence human IgG1 Fc region.
21. The immunoadhesin of claim 3 , wherein the variant human IgG Fc region comprises a T307A or T307Q substitution, wherein the numbering of the position of the substitution in the variant human IgG Fc region is that of the EU index as in Kabat.
22. The immunoadhesin of claim 3 , wherein the variant human IgG Fc region is a variant human IgG1 Fc region and wherein the variant Fc region has increased human neonatal Fc receptor (FcRn) binding affinity compared to a native sequence human IgG1 Fc region.
23. An isolated host cell comprising a nucleic acid encoding the antibody of claim 2 .
24. An isolated host cell comprising a nucleic acid encoding the immunoadhesin of claim 3 .
25. A method for producing an antibody comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased FcRn binding affinity, wherein the variant Fc region comprises an amino acid substitution at position 307, wherein the numbering of the position in the variant Fc region is that of the EU index as in Kabat, and wherein the method comprises culturing the host cell of claim 23 so that the antibody is expressed from the nucleic acid.
26. The method of claim 25 , further comprising recovering the antibody from the host cell culture.
27. A method for producing an immunoadhesin comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased FcRn binding affinity, wherein the variant Fc region comprises an amino acid substitution at position 307, wherein the numbering of the position in the variant Fc region is that of the EU index as in Kabat, and wherein the method comprises culturing the host cell of claim 24 so that the immunoadhesin is expressed from the nucleic acid.
28. The method of claim 27 , further comprising recovering the immunoadhesin from the host cell culture.
29. A antibody produced by the method of claim 25 .
30. An immunoadhesin produced by the method of claim 27 .