Pharmaceutical active conjugates

• US 6,342,225 B1
• Filed: 07/18/2000
• Issued: 01/29/2002
• Est. Priority Date: 08/13/1993
• Status: Expired due to Term

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Deutsches Krebsforschungsinstitut, Kings College London (University of London)
• Inventors: Sundermann, Erik, Eckey, Heike, Jones, Henry R., Schuttler, Achim, Shojaee-Moradi, Fariba, Brandenburg, Dietrich, Sonksen, Peter Henri
• Primary Examiner(s): Weddington, Kevin E.
• Application Number:
  US09/618,215
• Time in Patent Office: 560 Days
• Field of Search: 530/303, 530/389.2, 530/391.7, 424/193.1, 514/3
• US Class Current: 424/193.1
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: C07K 14/62 Insulins

Abstract

The invention provides an analogue of a pharmaceutical active whose molecular weight is less than 25,000 Daltons, the analogue comprising a pharmaceutical active whose molecular weight is less than 25,000 Daltons covalently linked to a pendant molecular group wherein as a result of the administration of the composition to the human or animal body an active complex having a molecular weight of 25,000 Daltons or greater is present in the human or animal circulatory system. The analogue is hepatoselective when administered to the circulatory system. Preferably the analogue is an insulin analogue comprising an insulin or functional equivalent thereof covalently linked to the pendant molecular group wherein the active complex is an insulin complex. Such an insulin analogue may be used in a method of insulin replacement therapy.

Claims

1. A conjugate compound derived from a pharmaceutical active whose molecular weight is less than 25,000 Daltons comprising:

a pharmaceutical active whose molecular weight is less than 25,000 Daltons covalently linked to a pendant molecular moiety, said pendant molecular moiety having an affinity for one or more binding proteins present in the human or animal circulatory system.

2. A conjugate compound according to claim 1, which is an insulin analogue and which comprises an insulin or functional equivalent thereof covalently linked to the pendant molecular moiety.

3. A conjugate compound according to claim 1, wherein the pendant molecular moiety is a naturally occurring hormone or an analogue of a naturally occurring hormone.

4. A conjugate compound according to claim 3, wherein the pendant molecular moiety is a thyroid hormone.

5. A conjugate compound according to claim 4 wherein the thyroid hormone is thyroxine.

6. A conjugate compound according to claim 2, wherein the pendant molecular moiety is a naturally occurring hormone or an analogue of a naturally occurring hormone.

7. A conjugate compound according to claim 6, wherein the pendant molecular moiety is a thyroid hormone.

8. A conjugate compound according to claim 7, wherein the thyroid hormone is thyroxine.

9. A conjugate compound according to claim 8 in which the thyroxine is 3, 5, 3′

, 5′

-tetraiodo-l-thyronine.

10. A conjugate compound according to claim 2, in which the insulin or functional equivalent thereof is covalently linked to the said pendant molecular moiety through its B1 terminal amino group.

11. A conjugate compound according to claim 1 in which the said binding protein is thryoxine binding globulin.

15. A conjugate compound according to claim 11, in which the pharmaceutical active is insulin or a functional equivalent thereof.

16. A conjugate compound according to claim 15, in which the said thyroid hormone is covalently bound to the B1 amine group of insulin or functional equivalent.

12. A conjugate compound derived from a pharmaceutical active whose molecular weight is less than 25,000 Daltons, comprising a pharmaceutical active covalently bound to a pendant molecular moiety which is a thyroid hormone or derivative analogue thereof.

13. A conjugate compound according to claim 12, wherein the thyroid hormone is thyroxine.

14. A conjugate compound according to claim 13, in which the thyroxine is 3, 5, 3′

, 5′

-tetraiodo-L-thyronine.

17. A pharmaceutical composition comprising a conjugate compound derived from a pharmaceutical active whose molecular weight is less than 25,000 Daltons comprising:

a pharmaceutical active whose molecular weight is less than 25,000 Daltons covalently linked to a pendant molecular moiety, said pendant molecular moiety having an affinity for one or more binding proteins present in the human or animal circulatory system.

18. A pharmaceutical composition comprising a conjugate compound derived from a pharmaceutical active whose molecular weight is less than 25,000 Daltons, comprising a pharmaceutical active covalently bound to a pendant molecular moiety which is a thyroid hormone or derivative or analogue thereof.