Modified glycoproteins

Patent metadata

Field	Value
Publication number	US-9650433-B2
Application number	US-201214118269-A
Country	US
Kind code	B2
Filing date	May 18, 2012
Priority date	May 20, 2011
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

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

First claim

The invention claimed is:

1. A preparation of glycoproteins, wherein at least 5% of the glycoproteins of the preparation comprise 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 an IgG heavy chain.

4. The preparation of claim 2 , 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 glycoproteins of the preparation comprise an Fc region comprising a sulfated glycan.

7. The preparation of claim 2 , wherein the sulfated glycan is singly sulfated.

8. The preparation of claim 2 , wherein the sulfated glycan is doubly sulfated.

9. The preparation of claim 1 , wherein the glycoproteins comprising an Fc region comprising a sulfated glycan have 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 glycoprotein comprising an Fc region that does not comprise a sulfated glycan.

10. A method of modifying activity of a preparation of glycoproteins, the method comprising:
providing a preparation of glycoproteins comprising an immunoglobulin Fc region comprising a glycan; and
sulfating the glycan of at least 5% of the glycoproteins of the preparation,
the glycoproteins 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 glycoprotein without a sulfated glycan.

11. A preparation of glycoproteins comprising an IgG heavy chain, wherein at least 5% of the glycoproteins of the preparation comprise a sulfated N-linked glycan at Asn297 of the IgG heavy chain, and wherein the glycoproteins comprising a sulfated glycan have an increased Fc receptor affinity compared to a reference glycoprotein without a sulfated glycan.

12. The preparation of claim 1 , wherein the glycoproteins of the preparation comprise an antibody selected from the group consisting of abciximab, adalimumab, alemtuzumab, basiliximab, bevacizumab, cetuximab, certolizumab, daclizumab, eculizumab, efalizumab, gemtuzumab, ibritumomab, infliximab, muromonab, natalizumab, omalizumab, palivizumab, panitumumab, ranibizumab, rituximab, tositumomab, and trastuzumab.

13. The method of claim 10 , wherein the sulfated glycan is linked to Asn297 of an IgG heavy chain.

14. The method of claim 10 , wherein the glycoproteins of the preparation comprise an antibody selected from the group consisting of abciximab, adalimumab, alemtuzumab, basiliximab, bevacizumab, cetuximab, certolizumab, daclizumab, eculizumab, efalizumab, gemtuzumab, ibritumomab, infliximab, muromonab, natalizumab, omalizumab, palivizumab, panitumumab, ranibizumab, rituximab, tositumomab, and trastuzumab.

Assignees

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

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• C07K2319/91

  containing a motif for glycosylation · CPC title

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K2319/40

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