Polymer excipients for biopharmaceutical formulations

Patent metadata

Field	Value
Publication number	US-11945892-B2
Application number	US-202217962252-A
Country	US
Kind code	B2
Filing date	Oct 7, 2022
Priority date	Apr 17, 2020
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

A polyacrylamide-based copolymer reduces or prevents aggregation of biologic molecules including proteins, peptides, and nucleic acids, and lipid-based vehicles such as liposomes, lipid nanoparticles, polymerosomes, and micelles, in aqueous formulations at hydrophobic interfaces, thereby increasing the thermal stability of the molecules in the formulation. Methods and compositions comprising the copolymer and a protein or the copolymer and insulin can be used for treating conditions including diabetes.

First claim

The invention claimed is:

1. A polyacrylamide-based copolymer comprising:
a random copolymer consisting of:
a water-soluble carrier monomer selected from N-(3 methoxypropyl)acrylamide (MPAM) and 4-acryloylmorpholine (MORPH); and
a functional dopant monomer that is N-isopropylacrylamide (NIP),

wherein the random copolymer comprises from 10% to 28% by weight of NIP.

2. The copolymer of claim 1 , wherein the water-soluble carrier monomer is MORPH.

3. The copolymer of claim 2 , wherein the copolymer comprises from 20% to 26% by weight of NIP.

4. The copolymer of claim 1 , wherein the water-soluble carrier monomer is MPAM.

5. The copolymer of claim 1 , wherein the degree of polymerization is from 10 to 500.

6. The copolymer of claim 1 , wherein the molecular weight of the copolymer is from 1,000 to 50,000 g/mol.

7. The copolymer of claim 1 , wherein:
the degree of polymerization is from 20 to 200; and
the molecular weight of the copolymer is from 2,000 to 10,000 g/mol.

8. The copolymer of claim 1 , wherein
the average molecular weight (Mn) of the copolymer is from 1,000 g/mol to 30,000 g/mol; and
the degree of polymerization of the copolymer is from 10 to 250.

9. The copolymer of claim 8 , wherein the water-soluble carrier monomer is MORPH.

10. The copolymer of claim 9 , wherein the copolymer comprises from 20% to 26% by weight of NIP.

11. The copolymer of claim 9 , wherein the copolymer comprises 23% by weight of NIP.

12. The copolymer of claim 9 , wherein the copolymer comprises:
74% to 80% by weight of MORPH; and
20% to 26% by weight of NIP;
the average molecular weight (Mn) of the copolymer is from 1,000 g/mol to 5,000 g/mol; and
the degree of polymerization of the copolymer is 10 to 50.

13. The copolymer of claim 2 , wherein the copolymer comprises 77% by weight of MORPH and 23% by weight of NIP.

14. A polyacrylamide-based copolymer comprising:
a water-soluble carrier monomer selected from MPAM and MORPH; and
a functional dopant monomer that is N-phenylacrylamide (PHE).

15. The copolymer of claim 14 , wherein the water-soluble carrier monomer is MPAM.

16. The copolymer of claim 14 , wherein the water-soluble carrier monomer is MORPH.

17. The copolymer of claim 14 , wherein the copolymer comprises from 2% to 16% by weight of PHE.

18. The copolymer of claim 14 , wherein:
the degree of polymerization is from 10 to 500; and
the molecular weight of the copolymer is from 1,000 to 50,000 g/mol.

19. The copolymer of claim 18 , wherein:
the degree of polymerization is from 20 to 200; and
the molecular weight of the copolymer is from 2,000 to 10,000 g/mol.

20. A polyacrylamide-based copolymer consisting of:
a water-soluble carrier monomer that is N-(3-methoxypropyl)acrylamide (MPAM); and
a functional dopant monomer that is N-isopropylacrylamide (NIP).

21. The copolymer of claim 20 , wherein the copolymer is a random copolymer that comprises from 2% to 30% by weight of NIP.

22. The copolymer of claim 20 , wherein:
the degree of polymerization is from 10 to 500; and
the molecular weight of the copolymer is from 1,000 to 50,000 g/mol.

23. The copolymer of claim 22 , wherein:
the degree of polymerization is from 20 to 200; and
the molecular weight of the copolymer is from 2,000 to 10,000 g/mol.

Assignees

• Univ Leland Stanford Junior
• The Board Of Trustees Of The Leland Stanford Junior Univeristy

Inventors

• Appel Eric A
• Maikawa Caitlin
• Mann Joseph L

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K38/22

  Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35) · CPC title

• A61K38/28

  Insulins · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• C08F2/38

  Polymerisation using regulators, e.g. chain terminating agents {, e.g. telomerisation} · CPC title