Anti-inflammatory polypeptides

Patent metadata

Field	Value
Publication number	US-9845358-B2
Application number	US-201514638905-A
Country	US
Kind code	B2
Filing date	Mar 4, 2015
Priority date	Dec 19, 2011
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

This invention concerns anti-inflammatory agents, compositions, and methods for treating inflammatory disorders.

First claim

What is claimed is:

1. method of increasing a level of regulatory T (T reg ) cells in a subject in need thereof, comprising administering to the subject an effective amount of
an isolated polypeptide, or a nucleic acid encoding the isolated polypeptide, comprising a modified sequence, wherein the IgG Fc region comprises the sequence of SEQ ID NO: 1, and wherein the modified sequence is at least 95% identical to SEQ ID NO: 1 and has a F to A mutation at a position corresponding to F32 of SEQ ID NO: 1.

2. The method of claim 1 , wherein the subject has an inflammatory disease.

3. The method of claim 2 , wherein the inflammatory disease is an autoimmune disease.

4. The method of claim 3 , wherein the autoimmune disease is a T cell-mediated autoimmune disease.

5. The method of claim 4 , wherein the T cell-mediated autoimmune disease is selected from the group consisting of multiple sclerosis and type I diabetes.

6. The method of claim 1 , wherein the isolated polypeptide has an ability to bind to Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN), hFcγRIIA, or hFcγRIIB.

7. The method of claim 6 , wherein the isolated polypeptide has an ability to bind to hFcγRIIA or hFcγRIIB at a K D of 2×10 −5 M or lower.

8. The method of claim 1 , wherein the modified sequence is (a) substantially free of sialylation or (b) sialylated at a level lower than that of IgG of the subject.

9. The method of claim 1 , wherein the modified sequence is at least 95% identical to SEQ ID NO: 2.

10. A method of treating a T cell-mediated autoimmune disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of
an isolated polypeptide, or a nucleic acid encoding the isolated polypeptide, comprising a modified sequence, wherein the modified sequence is at least 95% identical to SEQ ID NO: 1and has a F-to-A mutation at a position corresponding to position F32 of SEQ ID NO: 1, and wherein the first or second isolated polypeptide has an ability to bind to DC-SIGN, hFcγRIIA, or hFcγRIIB.

11. The method of claim 10 , wherein the T cell-mediated autoimmune disease is selected from the group consisting of multiple sclerosis and type I diabetes.

12. The method of claim 10 , wherein the isolated polypeptide has an ability to bind to hFcγRIIA or hFcγRIIB at a K D of 2×10 −5 M or lower.

13. The method of claim 10 , wherein the modified sequence is (a) substantially free of sialylation or (b) sialylated at a level lower than that of IgG of the subject.

14. The method of claim 10 , wherein the modified sequence is at least 95% identical to SEQ ID NO: 2.

Assignees

• Ravetch Jeffrey V
• Pincetic Andrew
• Univ Rockefeller

Inventors

• Ravetch Jeffrey V
• Pincetic Andrew

Classifications

• C07K2318/00

  Antibody mimetics or scaffolds · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K2317/72

  Increased effector function due to an Fc-modification · CPC title

• C07K16/2851 Primary

  against the lectin superfamily, e.g. CD23, CD72 · CPC title