.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,787,336

« Back to Dashboard

Details for Patent: 6,787,336

Title: DNA encoding growth hormone antagonists
Abstract:The present invention relates to DNA molecules which encode antagonists of vertebrate growth hormones obtained by mutation of at least the amino acid corresponding to Glu-119 in bovine growth hormone. The DNA molecules may be used to express the antagonists, either in cell culture, or in the cells of the patient of interest. The antagonist so expressed may be used to inhibit GH activity in a subject.
Inventor(s): Kopchick; John J. (Athens, OH), Chen; Wen Y. (Athens, OH)
Assignee: Ohio University/Edison Biotechnology Institute (Athens, OH)
Filing Date:Jun 07, 1995
Application Number:08/488,164
Claims:1. A non-naturally occurring DNA molecule comprising a coding sequence encoding a vertebrate growth hormone variante comprising an amino acid substitution of an amino acid, other than glycine or alanine, for the amino acid of said vertebrate growth hormone at the position corresponding to the glycine at position 119 of bovine growth hormone, wherein the growth hormone variant has vertebrate growth hormone inhibitory activity, with the proviso that said variant does not correspond to human growth hormone with all of the following substitutions and no others: Y111V, L113I, K115E, D116Q, E118K, E119R, G120L, Q122E, T123G, G126L, R127I and E129S.

2. A non-naturally occurring DNA molecule comprising a coding sequence encoding a vertebrate growth hormone variant comprising lysine at the position corresponding to the glycine at position 119 of bovine growth hormone, wherein the growth hormone variant has vertebrate growth hormone inhibitory activity.

3. A non-naturally occurring DNA molecule comprising a coding sequence encoding a vertebrate growth hormone variant comprising arginine at the position corresponding to the glycine at position 119 of bovine growth hormone, wherein the growth hormone variant has vertebrate growth hormone inhibitory activity.

4. A non-naturally occurring nucleic acid molecule which encodes a variant of a vertebrate growth hormone, wherein the variant comprises an amino acid sequence which is at least 80% identical to the native vertebrate growth hormone amino acid sequence, and wherein the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is an amino acid other than glycine or alanine, said variant having growth hormone receptor antagonist activity, with the proviso that said antagonist is not human growth hormone having all of the following substitutions and no others: Y111V, L113I, K115E, D116Q, E118K, E119R, G120L, Q122E, T123G, G126L, R127I and E129S.

5. The nucleic acid molecule of claim 4 which is a DNA molecule.

6. The DNA molecule of claim 5, further comprising a promoter operably linked to said coding sequence whereby said variant may be expressed in a host cell compatible with said promoter.

7. The DNA molecule of claim 6, wherein the promoter is a regulatable promoter.

8. The DNA molecule of claim 6 which is a retroviral vector.

9. The DNA molecule of claim 6 which is a linearized DNA.

10. A cell transformed by the DNA molecule of claim 6, and which expresses said variant.

11. A method of producing a mammalian growth hormone variant having growth hormone receptor antagonist activity, which comprises maintaining cells of claim 10 under conditions conducive to the experssion of said variant.

12. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is arginine.

13. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is tryptophan.

14. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is proline.

15. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is lysine.

16. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is leucine.

17. The molecule of claim 5 where the vertebrate growth hormone is a mammalian growth hormone.

18. The nucleic acid molecule of claim 17 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is arginine.

19. The nucleic acid molecule of claim 17 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is tryptophan.

20. The nucleic acid molecule of claim 17 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is proline.

21. The nucleic acid molecule of claim 17 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is lysine.

22. The nucleic acid molecule of claim 17 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is leucine.

23. The nucleic acid molecule of claim 17 in which the mammalian growth hormone is human growth hormone.

24. The nucleic acid molecule of claim 23 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is arginine.

25. The nucleic acid molecule of claim 23 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is tryptophan.

26. The nucleic acid molecule of claim 23 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is proline.

27. The nucleic acid molecule of claim 23 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is lysine.

28. The nucleic acid molecule of claim 23 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is leucine.

29. The nucleic acid molecule of claim 5 in which the amino acid position corresponding to amino acid Gly119 of bovine growth hormone is not proline.

30. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is selected from the group consisting of proline, glutamic acid, valine, glutamine, histidine, methionine, isoleucine, leucine, lysine, arginine, phenylalanine, tyrosine and tryptophan.

31. The nucleic acid molecule of claim 5 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is selected from the group consisting of leucine, isoleucine, lysine, arginine, phenylalanine, tyrosine and tryptophan.

32. A non-naturally occurring nucleic acid molecule which encodes a variant of a vertebrate growth hormone, wherein the variant comprises an amino acid sequence which is at least 80% identical to the native vertebrate growth hormone amino acid sequence, and wherein the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is an amino acid other than glycine or alanine, said variant having growth hormone receptor antagonist activity, where said vertebrate growth hormone is selected from the group consisting of bovine, porcine, ovine, rat, flounder, yellowtail, tuna, salmon and chicken growth hormones.

33. The nucleic acid molecule of claim 32 which is a DNA molecule.

34. The nucleic acid molecule of claim 33 which the mammalian growth hormone is bovine growt hormone.

35. The nucleic acid molecule of claim 33 in which the mammalian growth hormone is porcine growth hormone.

36. The nucleic acid molecule of claim 33 in which the mammalian growth hormone is ovine growth hormone.

37. The nucleic acid molecule of claim 33 in which the mammalian growth hormone is rat growth hormone.

38. The nucleic acid molecule of claim 33 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is arginine.

39. The nucleic acid molecule of claim 33 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is tryptophan.

40. The nucleic acid molecule of claim 33 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is proline.

41. The nucleic acid molecule of claim 33 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is lysine.

42. The nucleic acid molecule of claim 33 in which the amino acid at the position corresponding to amino acid Gly 119 of bovine growth hormone is leucine.

43. A non-naturally occurring nucleic acid molecule which encodes a variant of a mammalian growth hormone, wherein the variant comprises an amino acid sequence which is at least 80% identical to the native mammalian growth hormone amino acid sequence, and wherein the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is an amino acid other than glycine or alanine, said variant having growth hormone receptor antagonist activity, where said variant has an alpha helix, corresponding to the third alpha helix (AAs 106-129) of bovine growth hormone, which is at least 80% identical, but not completely identical, to the alpha helix of said mammalian growth hormone which corresponds to the third alpha helix (AAs 106-129) of bovine growth hormone.

44. The nucleic acid molecule of claim 43 in which the mammalian growth hormone is human growth hormone.

45. The nucleic acid molecule of claim 43 in which the mammalian growth hormone is bovine growth hormone.

46. The nucleic acid molecule of claim 43 in which the amino acid position corresponding to amino acid Gly119 of bovine growth hormone is arginine.

47. The nucleic acid molecule of claim 43 in which the amino acid position corresponding to amino acid Gly119 of bovine growth hormone is tryptophan.

48. The nucleic acid molecule of claim 43 in which the amino acid position corresponding to amino acid Gly119 of bovine growth hormone is proline.

49. The nucleic acid molecule of claim 43 in which the amino acid position corresponding to amino acid Gly119 of bovine growth hormone is lysine.

50. The nucleic acid molecule of claim 43 in which the amino acid position corresponding to amino acid Gly119 of bovine growth hormone is leucine.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc