Oral administration of therapeutic agent coupled to transporting agent induces tolerance

• US 20040014704A1
• Filed: 12/18/2002
• Published: 01/22/2004
• Est. Priority Date: 07/18/2002
• Status: Abandoned Application

• Current Assignee: NeoX, Inc.
• Original Assignee: NeoX, Inc.
• Inventors: Hortelano, Gonzalo, Vargas, Andrew Gomez
• Application Number:
  US10/323,372
• Publication Number:
  US 20040014704A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/6927 the form being a solid microparticle having no hollow or gas-filled cores
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 48/0025 wherein the non-active part clearly interacts with the delivered nucleic acid
• CPC Class Codes: A61K 48/0041 the non-active part being polymeric
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5052 Proteins, e.g. albumin
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention is directed toward a method for the induction of tolerance to a foreign transgene or a self-antigen in an animal host by administration of a composition to an animal host via a natural gastrointestinal pathway. Additionally, the present method can eliminate a pre-existing immune response in an animal host. The composition administered when carrying out the method achieves widespread distribution, systemic expression and sustained delivery of a genetic material in an animal host. More particularly, the invention discloses a method useful for both eliciting tolerance and for abrogation of a pre-existing immune response by oral administration of a genetic material.

Claims

1. A method for inducing tolerance in an animal host by administration of a composition to said animal host via a natural gastrointestinal pathway, said composition comprising:

at least one compound including an amine group; and

at least one genetic material;

said at least one compound and at least one genetic material coupled in a manner effective to enable widespread distribution, systemic expression and sustained delivery via said natural gastrointestinal pathway thereby inducing tolerance in an animal host.

2. The method of claim 1 wherein said at least one genetic material comprises a complete transcriptional unit.

3. The method of claim 2 wherein said complete transcriptional unit is effective for ubiquitous expression of said genetic material.

4. The method of claim 2 wherein said complete transcriptional unit is effective for tissue specific expression of said genetic material.

5. The method of claim 1 wherein said administration is accomplished rectally.

6. The method of claim 1 wherein said administration is accomplished orally and said method further includes, subsequent to coupling, a step of combining said compound containing an amine group and said genetic material with a protective agent in a manner effective to protect said composition during traversal of said natural gastrointestinal pathway.

7. A method for reducing a pre-existing immune response in an animal host by administration of a composition to said animal host via a natural gastrointestinal pathway, said composition comprising:

at least one compound including an amine group; and

at least one genetic material;

said at least one compound and at least one genetic material coupled in a manner effective to enable widespread distribution, systemic expression and sustained delivery via said natural gastrointestinal pathway thereby reducing a pre-existing immune response in an animal host.

8. The method of claim 7 wherein said at least one genetic material comprises a complete transcriptional unit.

9. The method of claim 8 wherein said complete transcriptional unit is effective for ubiquitous expression of said genetic material.

10. The method of claim 8 wherein said complete transcriptional unit is effective for tissue specific expression of said genetic material.

11. The method of claim 7 wherein said administration is accomplished rectally.

12. The method of claim 7 wherein said administration is accomplished orally and said method further includes, subsequent to coupling, a step of combining said compound containing an amine group and said genetic material with a protective agent in a manner effective to protect said composition during traversal of said natural gastrointestinal pathway.

13. A method for inducing tolerance in an animal host by administration of a composition to a targeted tissue of said animal host via a natural gastrointestinal pathway, said composition comprising:

at least one transporting agent effective for transporting a genetic material via said natural gastrointestinal pathway;

and at least one genetic material effective for expression in said targeted tissue;

said at least one transporting agent and at least one genetic material coupled in a manner effective to enable widespread distribution, systemic expression and sustained delivery as a result of cellular uptake subsequent to passage via said natural gastrointestinal pathway thereby inducing tolerance in an animal host.

14. The method of claim 13 wherein said at least one transporting agent is a compound containing an amine group which facilitates widespread in vivo distribution of said at least one genetic material upon coupling therewith.

15. The method of claim 13 wherein said at least one transporting agent is a polypeptide.

16. The method of claim 13 wherein said at least one genetic material comprises a complete transcriptional unit.

17. The method of claim 16 wherein said complete transcriptional unit is effective for ubiquitous expression of said at least one genetic material.

18. The method of claim 16 wherein said complete transcriptional unit is effective for tissue specific expression of said at least one genetic material.

19. The method of claim 13 wherein said administration is accomplished rectally.

20. The method of claim 13 wherein said administration is accomplished orally and said method further includes, subsequent to coupling, a step of combining said compound containing an amine group and said genetic material with a protective agent in a manner effective to protect said composition during traversal of said natural gastrointestinal pathway.

21. A method for reducing a pre-existing immune response in animal host by administration of a composition to a targeted tissue of said animal host via a natural gastrointestinal pathway, said composition comprising;

at least one transporting agent effective for transporting a genetic material via said natural gastrointestinal pathway;

and at least one genetic material effective for expression in said targeted tissue;

said at least one transporting agent and said at least one genetic material coupled in a manner effective to enable widespread distribution, systemic expression and sustained delivery as a result of cellular uptake subsequent to passage via said natural gastrointestinal pathway thereby reducing a pre-existing immune response in an animal host.

22. The method of claim 21 wherein said at least one transporting agent is a compound containing an amine group which facilitates widespread in vivo distribution of said at least one genetic material upon coupling therewith.

23. The method of claim 21 wherein said at least one transporting agent is a polypeptide.

24. The method of claim 21 wherein said at least one genetic material comprises a complete transcriptional unit.

25. The method of claim 24 wherein said complete transcriptional unit is effective for ubiquitous expression of said at least one genetic material.

26. The method of claim 24 wherein said complete transcriptional unit is effective for tissue specific expression of said at least one genetic material.

27. The method of claim 21 wherein said administration is accomplished rectally.

28. The method of claim 21 wherein said administration is accomplished orally and said method further includes, subsequent to coupling, a step of combining said compound containing an amine group and said genetic material with a protective agent in a manner effective to protect said composition during traversal of said natural gastrointestinal pathway.

29. A method for inducing tolerance in an animal host by administration of a composition to said animal host via a natural gastrointestinal pathway thereby enabling intracellular expression of a genetic material, comprising in combination:

at least one compound effective for protecting said genetic material within said natural gastrointestinal pathway;

at least one transporting agent effective for transporting a genetic material via said natural gastrointestinal pathway;

and at least one genetic material effective for intracellular expression;

said at least one transporting agent and at least one genetic material coupled in a manner effective to enable widespread distribution, systemic delivery and sustained expression as a result of cellular uptake subsequent to passage via said natural gastrointestinal pathway;

whereby intracellular expression of said at least one genetic material occurs subsequent to said cellular uptake thereby inducing tolerance in an animal host.

30. The method of claim 29 wherein said at least one transporting agent is a compound containing an amine group which facilitates widespread in viva distribution of said at least one genetic material upon coupling therewith.

31. The method of claim 29 wherein said at least one transporting agent is a polypeptide.

32. The method of claim 29 wherein said at least one genetic material comprises a complete transcriptional unit.

33. The method of claim 32 wherein said complete transcriptional unit is effective for ubiquitous expression of said at least one genetic material.

34. The method of claim 32 wherein said complete transcriptional unit is effective for tissue specific expression of at least one genetic material.

35. A method for reducing a pre-existing immune response in an animal host by administration of a composition to said animal host via a natural gastrointestinal pathway thereby enabling intracellular expression of a genetic material, comprising in combination:

at least one compound effective for protecting said genetic material within said natural gastrointestinal pathway;

at least one transporting agent effective for transporting a genetic material via said natural gastrointestinal pathway;

and at least one genetic material effective for intracellular expression;

said at least one transporting agent and said at least one genetic material coupled in a manner effective to enable widespread distribution, systemic delivery and sustained expression as a result of cellular uptake subsequent to passage via said natural gastrointestinal pathway;

whereby intracellular expression of said at least one genetic material occurs subsequent to said cellular uptake thereby reducing a pre-existing immune response in an animal host.

36. The method of claim 35 wherein said at least one transporting agent is a compound containing an amine group which facilitates widespread in vivo distribution of said at least one genetic material upon coupling therewith.

37. The method of claim 35 wherein said at least one transporting agent is a polypeptide.

38. The method of claim 35 wherein said at least one genetic material comprises a complete transcriptional unit.

39. The method of claim 38 wherein said complete transcriptional unit is effective for ubiquitous expression of said at least one genetic material.

40. The method of claim 38 wherein said complete transcriptional unit is effective for tissue specific expression of at least one genetic material.