Conjugates of a factor VIII moiety having an oxime-containing linkage

Patent metadata

Field	Value
Publication number	US-11628205-B2
Application number	US-201716319759-A
Country	US
Kind code	B2
Filing date	Jul 21, 2017
Priority date	Jul 22, 2016
Publication date	Apr 18, 2023
Grant date	Apr 18, 2023

Abstract

The present disclosure provides conjugates comprising a Factor VIII moiety covalently attached via an oxime-containing linkage to a water-soluble polymer, such as for example, a polyethylene glycol polymer. Methods for preparing and for administering such conjugates, are also provided, as are water-soluble polymer oxyamine reagents useful for preparing the subject conjugates, among other things.

First claim

It is claimed:

1. A conjugate comprising a branched poly(ethylene glycol) polymer covalently attached via an oxime-containing linkage to a carbohydrate of a Factor VIII moiety, the conjugate having a structure selected from:

where (m′) or (n) for each of the branched structures above independently ranges from about 1 to about 4,000, X is a spacer comprising a chain of atoms and having an atom chain length of from 5 to 25 atoms, where at least one of the atoms is a heteroatom selected from 0, S, and NH, and FVIII is a glycosylated Factor VIII moiety comprising carbohydrate groups, where ˜CH-FVIII is a residue of a carbonyl group of an oxidized carbohydrate on the Factor VIII moiety.

2. The conjugate of claim 1 , wherein each (m′) or (n) is about 227.

3. The conjugate of claim 1 , wherein the Factor VIII moiety is glycosylated human recombinant B-domain deleted Factor VIII.

4. The conjugate of claim 1 , wherein the Factor VIII moiety is glycosylated human recombinant full length Factor VIII.

5. A composition comprising a conjugate of claim 1 and a pharmaceutically acceptable excipient.

6. A composition comprising a conjugate having a structure according to claim 1 , wherein the average degree of PEGylation for conjugates comprised in the composition is in a range from 1 to 3.5.

7. The conjugate of claim 1 , wherein the weight average molecular weight of the branched poly(ethylene glycol) polymer ranges from greater than 5,000 Daltons to 100,000 Daltons.

8. The conjugate of claim 1 , wherein the branched poly(ethylene glycol) polymer has a weight-average molecular weight between 2,000 Daltons and 85,000 Daltons.

Assignees

• Nektar Therapeutics

Inventors

• Bossard Mary J
• Sheng Dawei

Classifications

• A61K47/54

  the modifying agent being an organic compound · CPC title

• C08G65/33396

  having oxygen in addition to nitrogen · CPC title

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C08G65/33306

  acyclic · CPC title

• C08G65/3314

  cyclic · CPC title