Sialylated glycoproteins

Patent metadata

Field	Value
Publication number	US-2016257754-A1
Application number	US-201415028917-A
Country	US
Kind code	A1
Filing date	Oct 14, 2014
Priority date	Oct 16, 2013
Publication date	Sep 8, 2016
Grant date	—

Abstract

Pharmaceutical preparations containing polypeptides having particular sialylation patterns, and methods for the treatment of immune-related thrombocytopenia with such preparations, are described.

First claim

What is claimed is:

1 . A pharmaceutical preparation formulated for subcutaneous administration, said preparation comprising polypeptides comprising an Fc region, wherein at least 50% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages.

2 . The pharmaceutical preparation of claim 1 , wherein said polypeptides are present in said pharmaceutical preparation at a concentration of 50-250 mg/mL.

3 . The pharmaceutical preparation of claim 1 , wherein less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,3 arm by way of a NeuAc-α 2,6-Gal terminal linkage.

4 . The pharmaceutical preparation of claim 1 , wherein less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,6 arm by way of a NeuAc-α 2,6-Gal terminal linkage.

5 . A pharmaceutical preparation comprising polypeptides having an Fc region, wherein at least 50% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages and less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,3 arm by way of a NeuAc-α 2,6-Gal terminal linkage.

6 . A pharmaceutical preparation comprising polypeptides having an Fc region, wherein at least 50% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages and less than 50% of branched glycans on the Fc region are mono-sialylated on the α 1,6 arm by way of a NeuAc-α 2,6-Gal terminal linkage.

7 . A pharmaceutical preparation comprising polypeptides having an Fc region, wherein at least 85% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages.

8 . The pharmaceutical preparation of claim 1 , wherein said polypeptides consist essentially of an Fc region.

9 . The pharmaceutical preparation of claim 1 , wherein said polypeptides further comprise a Fab region, a heterologous polypeptide sequence, or a non-polypeptide moiety.

10 . The pharmaceutical preparation of claim 9 , wherein at least 10% of branched glycans on the Fab region or heterologous polypeptide sequence of said polypeptides are mono-sialylated or di-sialylated.

11 . The pharmaceutical preparation of claim 9 , wherein less than 80% of branched glycans on the Fab region or heterologous polypeptide sequence of said polypeptides are mono-sialylated or di-sialylated.

12 . The pharmaceutical preparation of claim 1 , wherein said polypeptides are recombinant polypeptides.

13 . The pharmaceutical preparation of claim 1 , wherein said polypeptides are derived from plasma.

14 . The pharmaceutical preparation of claim 12 , wherein said polypeptides are IgG polypeptides or said polypeptides consist essentially of an Fc region derived from IgG polypeptides.

15 . A method of increasing reticulated platelets in a subject in need thereof, comprising administering to the subject a pharmaceutical preparation of claim 1 .

16 . A method of producing new platelets in a subject in need thereof, comprising administering to the subject a pharmaceutical preparation of claim 1 .

17 . A method of increasing reticulated platelets or producing new platelets in a subject in need thereof, comprising administering to the subject a pharmaceutical preparation comprising polypeptides comprising an Fc region, wherein at least 85% of branched glycans on the Fc region are di-sialylated by way of NeuAc-α 2,6-Gal terminal linkages.

18 . The method of claim 15 , wherein the subject is not being treated with thrombopoietin or a thrombopoietin receptor agonist or the subject did not respond to treatment with thrombopoietin or a thrombopoietin receptor agonist.

19 . The method of claim 15 , wherein the subject has immune-related thrombocytopenia.

20 . The method of claim 15 , further comprising, before and/or after the administering step, the step of determining the total platelet count and/or the reticulated platelet count in the subject.

21 . The method of claim 20 , further comprising, after the determining step, the step of adjusting the dose of the administered pharmaceutical preparation.

22 . The pharmaceutical preparation of claim 13 , wherein said polypeptides are IgG polypeptides or said polypeptides consist essentially of an Fc region derived from IgG polypeptides.

Assignees

• Momenta Pharmaceuticals Inc
• Momenta Pharmaceuticals Inc

Inventors

• Schultes Birgit C
• Chu Chia Lin
• Rutitzky Laura
• Zhang lynn
• Ling Leona E

Classifications

• C07K16/2848 Primary

  against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61 · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/00 Primary

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

• C07K2317/21

  from primates, e.g. man · CPC title