Glycopegylated factor ix

Patent metadata

Field	Value
Publication number	US-2017136104-A1
Application number	US-201715410014-A
Country	US
Kind code	A1
Filing date	Jan 19, 2017
Priority date	May 25, 2005
Publication date	May 18, 2017
Grant date	—

Abstract

Conjugates between Factor IX and PEG moieties. are disclosed in the present application. The conjugates are linked via a glycosyl linking group interposed between and covalently attached to the peptide and the modifying group. Conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto a glycosyl residue on the peptide. Also provided are methods for preparing the conjugates, methods for treating various disease conditions with the conjugates, and pharmaceutical formulations including the conjugates.

First claim

1 . A pharmaceutical composition comprising (i) a conjugate of a Factor IX variant of SEQ ID NO:1 and a modified sugar and (ii) a pharmaceutically acceptable excipient;
wherein the modified sugar comprises the formula

and
wherein
R 10 is a link to a —O-glycosyl residue or an amino acid of the Factor IX variant;
R 11 is selected from the group consisting of OH and NHC(O)CH 3 ;
R 12 is selected from the group consisting of H, C(O)CH 3 , NH, and NHC(O)CH 3 ;
R 13 is selected from the group consisting of OH and C(O)CH 3 ; and
R 14 is selected from the group consisting of H, C(O)CH 3 , NH, and NHC(O)CH 3 .

2 . The pharmaceutical composition according to claim 1 , wherein the Factor IX variant comprises an alanine in the first position.

3 . A method of stimulating blood coagulation in a mammal, comprising administering to said mammal the pharmaceutical composition according to claim 1 .

4 . A method of treating hemophilia in a subject, comprising administering to said subject the pharmaceutical composition according to claim 1 .

5 . The method according to claim 4 , wherein the hemophilia is hemophilia B.

6 . A method of preparing the conjugate of the pharmaceutical composition according to claim 1 , comprising conjugating the Factor IX variant and the modified sugar via chemoPEGylation.

Assignees

• Novo Nordisk As

Inventors

• Defrees Shawn
• Bayer Robert J
• Bowe Caryn
• Panneerselvam Krishnasamy

Classifications

• C12N9/644

  Coagulation factor IXa (3.4.21.22) · CPC title

• A61K38/4846 Primary

  Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38) · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61K47/549

  Sugars, nucleosides, nucleotides or nucleic acids · CPC title

• C12Y304/21022

  Coagulation factor IXa (3.4.21.22) · CPC title