Fc polypeptides with novel Fc ligand binding sites

• US 20050249723A1
• Filed: 12/21/2004
• Published: 11/10/2005
• Est. Priority Date: 12/22/2003
• Status: Abandoned Application

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Lazar, Gregory Alan
• Application Number:
  US11/022,289
• Publication Number:
  US 20050249723A1
• Time in Patent Office: Days
• US Class Current: 424/133.100
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2893 against CD52
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The present invention relates to Fc polypeptides with novel Fc receptor binding sites, and their application, particularly for therapeutic purposes.

Claims

1. A single polypeptide comprising two or more Fc regions linked contiguously.

2. A Fc polypeptide according to claim 1, wherein said Fc regions are of the same antibody isotype.

3. A Fc polypeptide according to claim 2, wherein said Fc regions are of an IgG isotype.

5. A Fc polypeptide according to claim 1, wherein a first Fc region is a different antibody isotype compared to a second Fc region.

6. A Fc polypeptide according to claim 5, wherein said first Fc region an IgG isotype and said second Fc region is an IgA isotype.

7. A Fc polypeptide according to claim 5, wherein said Fc polypeptide binds an Fcγ

R.

8. A Fc polypeptide according to claim 5, wherein said Fc polypeptide binds Fcα

RI.

9. A Fc polypeptide according to claim 8, wherein said Fc polypeptide also binds an Fcγ

R.

4. A Fc polypeptide according to claim 4, wherein said Fc ligand is an Fcγ

R.

10. Isolated nucleic acids encoding a single polypeptide comprising two or more Fc regions linked contiguously.

11. A isolated nucleic acids according to claim 10, wherein said encoded Fc regions are of the IgG isotype.

12. A isolated nucleic acids according to claim 10, wherein a first encoded Fc region is a different antibody isotype compared to a second encoded Fc region.

13. A isolated nucleic acids according to claim 10, wherein said encoded Fc polypeptide binds an Fcγ

R.

14. A isolated nucleic acids according to claim 10, wherein said encoded Fc polypeptide binds Fcα

RI.

15. A isolated nucleic acids according to claim 14, wherein said encoded Fc polypeptide also binds an Fcγ

R.

16. A variant Fc polypeptide comprising one or more amino acid substitutions compared to a parent Fc polypeptide, wherein said variant Fc polypeptide substantially binds to at least one Fc ligand that is not substantially bound by the parent Fc polypeptide.

17. A variant Fc polypeptide according to claim 16, wherein said variant Fc polypeptide binds Fcα

RI and one or more Fcγ

Rs.

18. A variant Fc polypeptide according to claim 17, wherein said variant Fc polypeptide is an IgG Fc polypeptide that binds Fcα

RI.

19. A Fc polypeptide according to claim 16, wherein said variant Fc polypeptide comprises at least one amino acid modification at a position selected from the group consisting of 250, 251, 252, 253, 314, 347, 380, 381, 382, 383, 384, 385, 426, 429, 430, 431, 432, 433, 434, 435, 436, 437, and 438, wherein the numbering is according to the EU index as in Kabat.

20. An Fc polypeptide according to claim 16, wherein said variant Fc polypeptide comprises at least one amino acid modification selected from the group consisting of T250L, M252L, I253G, L314N, Q347E, E380R, E382L, S383Q, N384G, an E insertion between positions 386 and 387, an L insertion between residues 386 and 387, G385S, S426M, H433P, N434L, H435A, and Y436F, wherein the numbering is according to the EU index as in Kabat.