BAL C-tail drug delivery molecules

• US 5,821,226 A
• Filed: 06/07/1995
• Issued: 10/13/1998
• Est. Priority Date: 12/01/1994
• Status: Expired due to Term

• Current Assignee: Oklahoma Medical Research Foundation
• Original Assignee: Oklahoma Medical Research Foundation
• Inventors: Wang, Chi-Sun, Tang, Jordan J. N.
• Primary Examiner(s): Lilling, Herbert J.
• Application Number:
  US08/482,262
• Time in Patent Office: 1,224 Days
• Field of Search: 514/12, 514/13, 514/14, 514/15, 514/16, 514/17, 514/18
• US Class Current: 424/450
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: C12N 9/20 Triglyceride splitting, e.g. by means of lipase

Abstract

Drug delivery conjugates of including a BAL C-tail peptide including all or a portion of the carboxy terminal region of human bile salt-activated lipase (BAL) conjugated to a biologically active substance are described. The C-tail peptide-drug conjugates, when orally ingested, compete with native BAL in binding to the intestinal surface, and, as a result, permit drug compositions to be delivered specifically to the intestine. Useful C-tail peptides are derivatives of the carboxy terminal region of BAL derived from all or portion of the region containing amino acid residues 539 to 722, and have a mucin-like structure containing at least three of the repeating proline-rich units of eleven amino acid residues each.

Claims

1. A method for delivering a therapeutic composition comprising:

orally administering to an individual in need thereof a therapeutically effective amount of a C-tail protein conjugated to a therapeutic composition, in combination with a pharmaceutical carrier acceptable for oral administration,

wherein the C-tail protein comprises at least four eleven amino acid repeats having at least three prolines present in the carboxy terminal region of human bile salt lipase as shown in Sequence ID No. 1 that binds to a specific receptor on intestinal cells.

2. The method of claim 1 wherein the C-tail protein comprises at least four eleven amino acid repeats present in amino acid residues 539 to 722 of Sequence ID No. 1.

3. The method of claim 1 wherein the C-tail protein further comprises the region of bile salt-activated lipase containing the catalytic site which has been inactivated.

4. The method of claim 1 wherein the C-tail protein further comprises at least three of the repeating regions of the primate, human, cat, dog or rodent bile salt-activated lipase.

5. The method of claim 1 wherein the C-tail protein comprises the at least four eleven amino acid proline-rich units.

6. The method of claim 1 wherein the C-tail protein is formed by the substitution of one or more amino acids of Sequence ID No. 1.

7. The method of claim 1 wherein the therapeutic composition is selected from the group consisting of proteins, carbohydrates, nucleic acids, nucleosides, nucleotides, liposomes, inorganic compounds, vitamins, drugs and minerals.

8. The method of claim 1 wherein the therapeutic compound is an enzyme.

9. The method of claim 8 wherein the enzyme catabolizes the compound ingested by the individual.

10. The method of claim 1, wherein the therapeutic composition is a polysaccharide.

11. The method of claim 1, wherein the therapeutic compound is an antigen.

12. The method of claim 1, wherein the therapeutic compound is a procaryotic or eucaryotic cell.

13. The method of claim 1, wherein the therapeutic compound is selected from the group consisting of nonsteroidal anti-inflammatory compounds, anesthetics, chemotherapeutic agents, immunosuppressive agents, steroids, antibiotics, antivirals, antifungals, steroidal anti-inflammatories, and anticoagulants.

16. The composition of claim 1 wherein the C-tail protein further comprises the region of bile salt-activated lipase containing the catalytic site which has been inactivated.

14. A composition for delivering a therapeutic composition comprising:

a therapeutically effective amount of a C-tail protein conjugated to a therapeutic composition, in combination with a pharmaceutical carrier acceptable for oral administration,

wherein the C-tail protein comprises at least four eleven amino acid repeats having at least three prolines present in the carboxy terminal region of human bile salt lipase as shown in Sequence ID No. 1, that binds to a specific receptor on intestinal cells.

15. The composition of claim 14 wherein the C-tail protein comprises at least four eleven amino acid repeats present in amino acid residues 539 to 722 of Sequence ID No. 1.

17. The composition of claim 14 wherein the C-tail protein further comprises at least three of the repeating regions of the primate, human, cat, dog or rodent bile salt-activated lipase.

18. The composition of claim 14 wherein the C-tail protein comprises at least ten eleven amino acid proline-rich units.

19. The composition of claim 14 wherein the C-tail protein is formed by the substitution of one or more amino acids of Sequence ID No. 1.

20. The composition of claim 14 wherein the therapeutic composition is selected from the group consisting of proteins, carbohydrates, nucleic acids, nucleosides, nucleotides, liposomes, inorganic compounds, vitamins, drugs and minerals.

21. The composition of claim 14 wherein the therapeutic compound is an enzyme.

22. The composition of claim 21 wherein the enzyme catabolizes the compound ingested by the individual.

23. The composition of claim 14, wherein the therapeutic composition is a polysaccharide.

24. The composition of claim 14, wherein the therapeutic compound is an antigen.

25. The composition of claim 14, wherein the therapeutic compound is a procaryotic or eucaryotic cell.

26. The composition of claim 14, wherein the therapeutic compound is selected from the group consisting of nonsteroidal anti-inflammatory compounds, anesthetics, chemotherapeutic agents, immunosuppressive agents, steroids, antibiotics, antivirals, antifungals, steroidal anti-inflammatories, and anticoagulants.

27. The composition of claim 14 wherein the carrier is a polymer or enteric encapsulating composition and the C-tail protein is incorporated onto or within the carrier.

28. The composition of claim 14 wherein the C-tail protein is in a dietary formulation for oral administration.

29. The composition of claim 14 wherein the C-tail protein is in the milk of a transgenic cow or sheep.