Modified glycoproteins

Patent metadata

Field	Value
Publication number	US-10377809-B2
Application number	US-201715483545-A
Country	US
Kind code	B2
Filing date	Apr 10, 2017
Priority date	May 20, 2011
Publication date	Aug 13, 2019
Grant date	Aug 13, 2019

Abstract

Sulfated glycoproteins, and methods of making and using such sulfated glycoproteins, are described.

First claim

The invention claimed is:

1. A preparation of abatacept, wherein at least 5% of the abatacept of the preparation comprises an Fc region comprising a sulfated glycan.

2. The preparation of claim 1 , wherein the sulfated glycan is linked to a CH2 domain of an IgG heavy chain.

3. The preparation of claim 2 , wherein the sulfated glycan is linked to Asn297 of the IgG heavy chain.

4. The preparation of claim 1 , wherein the sulfated glycan comprises a branched glycan.

5. The preparation of claim 2 , wherein the sulfated glycan comprises one or more of a sulfated N-acetylglucosamine, a sulfated galactose, or a sulfated N-acetylgalactosamine.

6. The preparation of claim 1 , wherein at least 10% of the abatacept of the preparation comprises an Fc region comprising a sulfated glycan.

7. The preparation of claim 1 , wherein the glycan is singly sulfated.

8. The preparation of claim 1 , wherein the glycan is doubly sulfated.

9. The preparation of claim 1 , wherein the abatacept comprising an Fc region comprising a sulfated glycan has a different Fc receptor affinity, Fc receptor specificity, complement activation activity, signaling activity, targeting activity, effector function, half-life, clearance, pro-inflammatory activity, anti-inflammatory activity, or transcytosis activity than a corresponding abatacept comprising an Fc region that does not comprise a sulfated Fc glycan.

10. The preparation of claim 9 , wherein the effector function is antibody dependent cellular cytotoxicity, complement dependent cytotoxicity, programmed cell death, or cellular phagocytosis.

11. The preparation of claim 9 , wherein the Fc receptor is an FcγRI, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, FcγRIV, or FcRn receptor.

12. The preparation of claim 11 , wherein the abatacept comprising an Fc region comprising a sulfated glycan binds to a macrophage, neutrophil, dendritic cell, B cell, natural killer cell, or eosinophil.

13. A method of modifying activity of a preparation of abatacept, the method comprising:
providing a preparation of abatacept comprising an immunoglobulin Fc region comprising a glycan; and
sulfating the glycan of at least 5% of the abatacept of the preparation,
the abatacept comprising the sulfated glycan having a different Fc receptor affinity, Fc receptor specificity, complement activation activity, signaling activity, targeting activity, effector function, half-life, clearance, pro-inflammatory activity, anti-inflammatory activity, or transcytosis activity than a corresponding abatacept that does not comprise a sulfated glycan.

Assignees

• Momenta Pharmaceuticals Inc

Inventors

• Bulik Dorota A
• Bosques Carlos J
• Collins Brian Edward
• Hains Maurice Gaston
• Washburn Nathaniel J
• Meador James
• Smith Sean
• Bhatnagar Naveen

Classifications

• C07K14/70521 Primary

  CD28, CD152 · CPC title

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title

• C07K2319/91

  containing a motif for glycosylation · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• C07K2319/74

  containing a fusion for binding to a cell surface receptor · CPC title