Protozoan variant-specific surface proteins (VSP) as carriers for oral drug delivery

Patent metadata

Field	Value
Publication number	US-9757471-B2
Application number	US-201314413189-A
Country	US
Kind code	B2
Filing date	Jul 5, 2013
Priority date	Jul 6, 2012
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

Abstract

The invention provides compositions for oral delivery and methods of treatment using VSP carriers, such as Giardia sp. variable surface proteins (VSP), to deliver therapeutic agents. VSP drug carriers can be combined with bioactive peptides, e.g., insulin, glucagon, or hGH, and be administered orally or mucosally. VSP carriers are resistant to acidic pHs and to proteolytic degradation and protect therapeutic agents from degradation in the gastrointestinal tract.

First claim

What is claimed is:

1. A method of delivering peptide hormone to-mucosal epithelial cells in a subject in need thereof comprising orally administering a therapeutic composition comprising a peptide hormone and a Giardia VSP (Variant-specific Surface Protein) carrier to the subject, wherein(i) the VSP carrier is bound non-covalently to the peptide hormone;(ii) the VSP carrier-bound peptide hormone is therapeutically effective;(iii) the VSP carrier-bound peptide hormone is more resistant to pH- mediated or enzymatic degradation than the same peptide hormone not bound to the same VSP carrier; and,(iv) the VSP carrier has at least 70% amino acid sequence identity with the sequence of the extracellular domain of a VSP from Giardia selected from VSP1267 (SEQ ID NO:490), VSP9B10 (SEQ ID NO:572), and VSPH7 (SEQ ID NO:504).

2. The method according to claim 1 , wherein the peptide hormone: VSP carrier molecule to molecule ratio ranges from about 10:1 to about 1:10.

3. The method according to claim 2 , wherein the peptide hormone: VSP carrier molecule to molecule ratio is about 3:1.

4. The method according to claim 2 , wherein the peptide hormone: VSP carrier molecule to molecule ratio is about 1:1.

5. The method according to claim 1 , wherein the VSP from Giardia is VSP 1267.

6. The method according to claim 1 , wherein the VSP carrier comprises the amino acid sequence of SEQ ID NO:2.

7. The composition according to claim 1 , wherein the VSP carrier consisting of the sequence of SEQ ID NO: 1.

8. The method according to claim 1 , wherein the VSP carrier further comprises a heterologous moiety.

9. The method according to claim 1 , wherein the peptide hormone is selected from the group consisting of insulin, human growth hormone, and glucagon, and a combination of two or more of said peptide hormones.

10. The method according to claim 1 , wherein the peptide hormone is a natural insulin, a recombinant insulin, an insulin analog, or a combination thereof.

11. The method according to claim 10 , wherein the insulin analog is a fast-acting insulin, a long-acting insulin, or a combination thereof.

12. The method according to claim 10 , wherein the insulin analog is insulin aspart, insulin glargine, or a combination thereof.

13. The method according to claim 1 , wherein the subject suffers from a hormone deficiency.

14. The method according to claim 13 , wherein the hormone deficiency is diabetes.

15. The method according to claim 1 , wherein the VSP carrier having at least 70% amino acid sequence identity with the sequence of the extracellular domain of VSP1267 (SEQ ID NO: 490), VSP9B10 (SEQ ID NO: 572), or VSPH7 (SEQ ID NO: 504) is selected from SEQ ID NOS: 58, 143, 163, 166, 167, 308, and 486, or a fragment thereof.

16. The method according to claim 1 , wherein the mucosal epithelial cells are intestinal, gastric, or oral mucosal epithelial cells.

Assignees

• Consejo Nac De Investig Cientificas Y Tecn (Conicet)
• Inserm (Institut Nat De La Sante Et De La Rech Medicale)
• Univ Catolica De Cordoba
• Hopitaux Paris Assist Publique
• Univ Pierre Et Marie Curie Paris 6
• Consejo Nac De Investig Cientificas Y Technicas (Conicet)

Inventors

• Klatzmann David
• Piaggio Eliane
• Lujan Hugo

Classifications

• A61Q19/00

  Preparations for care of the skin · CPC title

• A61K38/2013

  IL-2 · CPC title

• A61K38/27

  Growth hormone [GH], i.e. somatotropin · CPC title

• C07K14/44

  from protozoa · CPC title

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title