Fc region variants

• US 20040002587A1
• Filed: 02/20/2003
• Published: 01/01/2004
• Est. Priority Date: 02/20/2002
• Status: Abandoned Application

• Current Assignee: Applied Molecular Evolution, Inc. (Eli Lilly and Company)
• Original Assignee: Applied Molecular Evolution, Inc. (Eli Lilly and Company)
• Inventors: Allan, Barrett, Watkins, Jeffry D.
• Application Number:
  US10/370,749
• Publication Number:
  US 20040002587A1
• Time in Patent Office: Days
• US Class Current: 530/388.15
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/524 CH2 domain
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

The present invention provides polypeptide Fe region variants and oligonucleotides encoding Fc region variants. Specifically, the present invention provides compositions comprising novel Fc region variants, methods for identifying useful Fc region variants, and methods for employing Fc region variants for treating disease.

Claims

1. A composition comprising a variant of a parent polypeptide having at least a portion of an Fe region, wherein said variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of effector cells more effectively than said parent polypeptide and comprises at least one amino acid modification at position 280 in the Fe region.

2. The composition of claim 1, wherein said variant interacts with Fe gamma receptor III (Fcγ

RIII) with a higher assay signal than said parent polypeptide.

3. The composition of claim 1, wherein said variant interacts with Fe gamma receptor IIb (Fcγ

RIIb) with a lower assay signal than said parent polypeptide.

4. The composition of claim 1, wherein said variant comprises an antibody.

5. The composition of claim 4, wherein said antibody comprises an unmodified human framework.

6. The composition of claim 4, wherein said antibody is an anti-CD20 antibody.

7. The composition of claim 1, wherein parent polypeptide comprises a human IgG Fe region.

8. The composition of claim 1, wherein said parent polypeptide comprises a human IgG1, IgG2, IgG3, or IgG4 Fe region.

9. The composition of claim 1, wherein said amino acid modification is D280H.

10. The composition of claim 1, wherein said parent polypeptide comprises a CH2 region comprising SEQ ID NO:

23.

11. A composition comprising a variant of a parent polypeptide having at least a portion of an Fe region, wherein said variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of effector cells more effectively than said parent polypeptide and comprises at least one amino acid modification at position 290 in the Fe region.

12. The composition of claim 11, wherein said variant interacts with Fe gamma receptor III (Fcγ

RII) with a higher assay signal than said parent polypeptide.

13. The composition of claim 11, wherein said variant interacts with Fe gamma receptor IIb (Fcγ

RIIb) with a higher assay signal than said parent polypeptide.

14. The composition of claim 11, wherein said variant comprises an antibody.

15. The composition of claim 14, wherein said antibody comprises an unmodified human framework.

16. The composition of claim 14, wherein said antibody is an anti-CD20 antibody.

17. The composition of claim 11, wherein parent polypeptide comprises a human IgG Fe region.

18. The composition of claim 11, wherein said parent polypeptide comprises a human IgG1, IgG2, IgG3, or IgG4 Fe region.

19. The composition of claim 11, wherein said amino acid modification is K290S.

20. The composition of claim 11, wherein said parent polypeptide comprises a CH2 region comprising SEQ ID NO:

23.