RECOMBINANT HUMAN ALPHA-1-ANTITRYPSIN FOR THE TREATMENT OF INFLAMMATORY DISORDERS

• US 20140228301A1
• Filed: 12/19/2012
• Published: 08/14/2014
• Est. Priority Date: 12/19/2011
• Status: Abandoned Application

• Current Assignee: LFB USA, Inc. (Agence des Participations de l’Etat)
• Original Assignee: rEVO Biologics, Inc. (Agence des Participations de l’Etat)
• Inventors: Meade, Harry M., Bourdon, Paul R.
• Application Number:
  US14/342,170
• Publication Number:
  US 20140228301A1
• Time in Patent Office: Days
• US Class Current: 514/20.9
• CPC Class Codes: A01K 2217/052 inducing gain of function
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/8125 Alpha-1-antitrypsin

Abstract

In one aspect, the disclosure relates to compositions comprising alpha-1-antitrypsin (AAT) and the production thereof. In some embodiments, the AAT is recombinantly produced. The disclosure also relates to methods of administering compositions comprising alpha-1-antitrypsin (AAT).

Claims

1. A composition comprising alpha-1-antitrypsin (AAT), wherein the AAT is recombinantly produced.

2. The composition of claim 1, wherein the AAT is produced in mammary epithelial cells of a non-human mammal.

3. The composition of claim 1, wherein the AAT is produced in a transgenic non-human mammal.

4. The composition of claim 2 or claim 3, wherein the non-human mammal is a goat, sheep, bison, camel, cow, pig, rabbit, buffalo, horse, rat, mouse or llama.

5. The composition of claim 4, wherein the non-human mammal is a goat.

6. The composition of any one of claims 1-5, wherein the recombinantly produced AAT has enhanced deoxyhexose glycosylation compared to plasma-derived AAT.

7. The composition of any one of claims 1-6, wherein the recombinantly produced AAT has been modified to increase the sialylation on the AAT-glyco-motifs.

11. A composition comprising the AAT of any one of claims 1-10, further comprising milk.

12. A composition comprising the AAT of any one of claims 1-11, further comprising a pharmaceutically acceptable carrier.

13. Mammary gland epithelial cells that produce the AAT of the compositions of any one of claims 1-12.

14. A transgenic non-human mammal comprising the mammary gland epithelial cells of claim 13.

15. A method comprising administering the composition of any one of claims 1-12 to a subject in need thereof.

16. The method of claim 15, wherein the subject has alpha-1-antitrypsin deficiency.

17. The method of claim 15, wherein the subject has an inflammatory disorder.

18. The method of claim 17, wherein the inflammatory disorder is emphysema.

19. The method of any one of claims 15-18, wherein the composition is administered at a dose of from 30 mg/kg to about 60 mg/kg AAT.

20. The method of any one of claims 15-19, wherein the composition is administered intravenously.

21. The method of any one of claims 15-19, wherein the composition is administered by inhalation.

22. A method of reducing elastase activity in the lung, the method comprising administering the composition of any one of claims 1-12 to a subject in an amount sufficient to reduce elastase activity in the lung.

8. A composition comprising AAT wherein the AAT has a high level of deoxyhexose glycosylation.

9. A composition comprising AAT wherein the AAT has a high level of sialylation on the AAT-glyco-motifs.

10. A composition comprising AAT wherein the AAT has a high level of deoxyhexose glycosylation and a high level of sialylation on the AAT-glyco-motifs.