TH13496A - Insulin analogues for selective tissue type - Google Patents

Abstract

Analogues of human insulin have been revealed. These analogues are tissue-selective, with pharmaceutical formulations containing these invented analogues offering significant medical advantages over human insulin when used to treat diabetic patients. The analogues are modified at amino acids A12, A15, or A19, differing from the naturally occurring region at those positions, and are liver-selective. Furthermore, it was revealed that human insulin analogues are modified at amino acids A12 or A14, or at A10 and A13, differing from the naturally occurring region at those positions, and are periferal-selective. DNA and microbial sequences containing the coding sequences of human insulin analogues have also been provided, along with methods for preparing human insulin analogues.

Claims (52)

1. An analog of human insulin that contains a different amino acid segment at position A12 than the naturally occurring segment at this position. This analog is selectively metabolized by the liver. 2. An analog of human insulin contains an amino acid at position A19 that differs from the naturally occurring portion at this position in that it is not hydrophobic and that this analog is selectively metabolized. 3. An analog of human insulin containing an amino acid segment at position A12 that differs from the naturally occurring segment at that position, along with one or both of these segments—an amino acid segment at position A19 that differs from the naturally occurring segment at that position, and an amino acid segment at position A15 that differs from the naturally occurring segment at that position. This analog is selectively dependent on other components. 4. An analog of human insulin under claim 1, consisting of A12Gly. 5. An analog of human insulin under claim 2, comprising A19His. 6. An analog of human insulin under claim 2, comprising A19Gly. 7. Analogues of human insulin under claim 3, comprising A12Gly and A19His. 8. A human DNA sequence containing the code for the human insulin analog according to claim 1. 9. A human DNA sequence containing the code for the human insulin analog according to claim 2. 10. A human DNA sequence containing the code for the human insulin analog according to claim 3. 11. A microorganism consisting of a host cell containing a DNA sequence as per claim 8. 12. A microorganism consisting of a host cell containing a DNA sequence according to claim 9. 13. A microorganism consisting of a host cell with a DNA sequence according to claim 10. 14. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 11. 15. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 12. 16. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 13. 17. An analog of human insulin containing an amino acid segment at position A12 or a combination of amino acid segments at positions A10 and A13, where one or more of these segments differ from one or more naturally occurring segments at those positions, and where the analog is selectively periferential. 18. An analog of human insulin under claim 17, comprising A12Ala. 19. Analogues of human insulin under claim 17, comprising A10Pro and A13Trp. 20. A human DNA sequence containing the code for the human insulin analog under claim 17. 21. A microorganism consisting of a host cell containing a DNA coding organism, as per claim 20. 22. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 21. 23. A pharmaceutical formulation containing pharmaceutical filler material and a human insulin analog in amounts that provide the pharmaceutical effect as per claim 1. 24. A pharmaceutical formulation containing pharmaceutical filler material and a human insulin analog in amounts that provide the pharmaceutical effect as per claim 2. 25. A pharmaceutical formulation containing pharmaceutical filler material and a human insulin analog in amounts that provide the pharmaceutical effect as per claim 3. 26. A pharmaceutical formulation containing pharmaceutical filler and a human insulin analog in amounts that provide the pharmaceutical effect as per claim 17. 27. A method for treating animals consisting of administering, in response to the animal's needs, an analog of human insulin in a dose that provides the pharmacological effect as per Claim 1. 28. A method for treating animals consisting of administering the required animal an analog of human insulin in a dosage that provides the pharmacological effect as per claim 2. 29. A method for treating animals consisting of administering the required animal an analog of human insulin in a dosage that provides the pharmacological effect as per claim 3. 30. A method for treating animals consisting of administering the required animal an analog of human insulin in a dosage that provides the pharmacological effect as per claim 17. 31. A method for treating animals consisting of administering an insulin periferal analog of human insulin in pharmacologically effective doses to animals requiring treatment, where the amino acid fraction A14 differs from the naturally occurring amino acid and is phenylalanine. 32. The insulin analog of a person has an amino acid at position A12 that differs from the natural amino acid at that position, and the analog is selective for periferal. 33. The insulin analog of a person with an amino acid sequence at position A14 differs from the natural insulin analog at that position, and this analog is hepatoselective. 34. The insulin analog of a person with insulin at positions A12 and A14 differs from the natural insulin at those positions, and the analog is hepatoselective. 35. An analog of human insulin under claim 32, consisting of A12Thr. 36. An analog of human insulin under claim 33, consisting of A14Gly. 37. Analogues of human insulin under claim 34, comprising A12Thr and A14Gly. 38. A human DNA sequence containing the code for the human insulin analog under claim 32. 39. A human DNA sequence containing the code for the human insulin analog under claim 33. 40. A human DNA sequence containing the code for the human insulin analog under claim 34. 41. A microorganism consisting of a host cell containing a DNA coding entity, as per claim 38. 42. A microorganism consisting of a host cell containing a DNA coding entity, as per claim 39. 43. A microorganism consisting of cells that enter a home containing a DNA code, as per claim 40. 44. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 41. 45. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 42. 46. A procedure for preparing an analog of human insulin consisting of microbial culture as per claim 43. 47. A pharmaceutical formulation containing pharmaceutical filler material and a human insulin analog in amounts that provide the pharmaceutical effect as per claim 32. 48. A pharmaceutical formulation containing pharmaceutical additives and an analog of human insulin in amounts that produce the pharmaceutical effect as per claim 33. 49. A pharmaceutical formulation containing pharmaceutical additives and an analog of human insulin in amounts that produce the pharmaceutical effect as per claim 34. 50. A method for treating animals consisting of administering the required animal an analog of human insulin in a dosage that provides the pharmacological effect as per claim 32. 51. A method for treating animals consisting of administering the required animal an analog of human insulin in a dosage that provides the pharmacological effect as per claim 33. 52. A method for treating animals consisting of administering the required animal an analog of human insulin in a dosage that provides the pharmacological effect as per claim 34 (Clause 52, page 5, figure 9).