Compositions and methods for administering insulin or insulin-like protein to the brain

• US 10,188,739 B2
• Filed: 02/26/2015
• Issued: 01/29/2019
• Est. Priority Date: 02/27/2014
• Status: Active Grant

• Current Assignee: Xenetic Biosciences, Inc.
• Original Assignee: Xenetic Biosciences, Inc.
• Inventors: Jain, Sanjay, Genkin, Dmitry, Hoppe, Henry
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US14/632,967
• Publication Number:
  US 20150238620A1
• Time in Patent Office: 1,433 Days
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides a method of intranasal delivery of a pharmaceutical composition, comprising a polysaccharide derivative of insulin protein and a one or more pharmaceutically acceptable excipients, to a subject, wherein the insulin protein is delivered to the brain of the subject through the nasal mucosa.

Claims

1. A method of administering a therapeutically effective amount of an insulin to the brain of an individual, the method comprising intranasal administration of a pharmaceutical composition comprising a population of the insulin and/or an insulin-like protein attached to a polysialic acid where administration results in a therapeutically effective amount in the brain but not the serum of the individual.

2. The method according to claim 1, wherein the insulin is a natural insulin derived from an animal.

3. The method according to claim 2, wherein the natural insulin is derived from a human.

4. The method according to claim 1, wherein the insulin comprised SEQ ID NO:

1, SEQ ID NO;

2, or SEQ ID NO;

3.

5. The method according to claim 1, wherein the insulin-like protein comprises the A-chain/B-chain amino acid sequence combinations of SEQ ID NO:

3/SEQ ID NO;

4, or SEQ ID NO;

3/SEQ ID NO;

5, or SEQ ID NO;

3/SEQ ID NO;

6, or SEQ ID NO;

3/SEQ ID NO;

7, or SEQ ID NO;

3/SEQ ID NO;

8.

6. The method according to claim 1, wherein the polysialic acid is a homopolymeric form, or a heteropolymeric form.

7. The method according to claim 6, wherein the homopolymeric form includes an alternating alpha-2,8 linked polysialic acid.

8. The method according to claim 7, wherein the polysialic acid comprises about 40 to about 150 sialic acid units.

9. The method according to claim 6, wherein the heteropolymeric form includes an alternating alpha-2,8 alpha-2,9 linked polysialic acid.

10. The method according to claim 1, wherein the polysialic acid comprises about 2 to about 200 sialic acid units.

11. The method according to claim 10, wherein the polysialic acid comprises about 20 to about 175 sialic acid units.

12. The method according to claim 1, wherein the polysialic acid has an average molecular weight in the range of about 2 kDa to about 100 kDa.

13. The method according to claim 12, wherein the polysialic acid has an average molecular weight in the range of about 5 kDa to about 80 kDa.

14. The method according to claim 1, wherein the polysialic acid is attached to the protein by its reducing end terminal unit, its non-reducing terminal unit, or both.

15. The method according to claim 1, wherein the population of the insulin and/or an insulin-like protein attached to the polysialic acid has a polydispersity of about 1.05 to about 1.3.

16. The method according to claim 15, wherein the population of the insulin attached to the polysialic acid has a polydispersity of about 1.05 to about 1.2.

17. The method according to claim 1, wherein the insulin proteins having the polysialic acid attached to the N-terminus of the insulin protein is at least 70% of the total proteins of the population.

18. The method according to claim 1, wherein the insulin proteins having the polysialic acid attached to the N-terminus of the insulin protein is about 80% to about 100% of the total proteins of the population.

19. The method according to claim 1, wherein the population of the insulin and/or an insulin-like protein attached with a polysialic acid is administered to an individual at a dose of between about 0.6 mg/kg to about 3.0 mg/kg.