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Last Updated: March 28, 2024

Claims for Patent: 7,217,689


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Summary for Patent: 7,217,689
Title:Glycosylation analogs of erythropoietin
Abstract: Erythropoietin analogs having at least one additional site for glycosylation, or a rearrangement of at least one site for glycosylation are disclosed. The invention also relates to DNA sequences encoding said erythropoietin analogs, and recombinant plasmids and host cells for analog expression.
Inventor(s): Elliott; Steven G. (Newbury Park, CA), Byrne; Thomas E. (Arlington, VA)
Assignee: Amgen Inc. (Thousand Oaks, CA)
Application Number:08/479,892
Patent Claims:1. An analog of human erythropoietin having the in vivo biological activity of increasing hematocrit comprising an amino acid sequence which differs from the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO:26 at least by having one or more additional glycosylation site(s) and wherein a carbohydrate chain is attached to the additional site(s).

2. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO:26 except for one or more amino acid changes which provide for one or more additional glycosylation site(s) as compared to human erythropoietin, and the analog has more than four carbohydrate chains.

3. The analog of claims 1 or 2 wherein one additional glycosylation site is an N-linked glycosylation site having an N-linked carbohydrate chain attached thereto.

4. The analog of claims 1 or 2 wherein one additional glycosylation site is an O-linked glycosylation site having an O-linked carbohydrate chain attached thereto.

5. The analog of claims 1 or 2 which is the product of expression of an exogenous DNA sequence.

6. A DNA sequence encoding an analog of human erythropoietin according to any of claims 1 or 2.

7. A eucaryotic host cell transfected with a DNA sequence according to claim 6 in a manner allowing the host cell to express an analog of human erythropoietin.

8. A composition comprising an erythropoietin analog according to any of claims 1 or 2 together with a pharmaceutically acceptable diluent, adjuvant or carrier.

9. A method of increasing hematocrit in a patient in need thereof comprising administering a therapeutically effective amount of the composition of claim 8.

10. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO:26 except for one or more amino acid changes which provide for one or more additional glycosylation site(s) as compared to human erythropoietin, wherein one additional site is introduced at about position 30, 51, 57, 69, 88, 89, 136 or 138 and an N-linked carbohydrate chain is attached at said one additional site.

11. The analog of claim 10 wherein the one additional site is introduced at position 30.

12. The analog of claim 10 wherein the one additional site is introduced at position 51.

13. The analog of claim 10 wherein the one additional site is introduced at position 57.

14. The analog of claim 10 wherein the one additional site is introduced at position 69.

15. The analog of claim 10 wherein the one additional site is introduced at position 88.

16. The analog of claim 10 wherein the one additional site is introduced at position 89.

17. The analog of claim 10 wherein the one additional site is introduced at position 136.

18. The analog of claim 10 wherein the one additional site is introduced at position 138.

19. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO:26 except for one or more amino acid changes which provide for one or more additional glycosylation site(s) as compared to human erythropoietin, wherein one additional site is introduced at about position 123 or 125 and an O-linked carbohydrate chain is attached at said one additional site.

20. The analog of claim 19 wherein the one additional site is introduced at position 123.

21. The analog of claim 19 wherein the one additional site is introduced at position 125.

22. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO: 26 except for the amino acid changes selected from the group consisting of: Asn.sup.30Thr.sup.32 EPO; Asn.sup.51Thr.sup.53 EPO; Asn.sup.57Thr.sup.59 EPO; Asn.sup.69EPO; Asn.sup.69Thr.sup.71 EPO; Ser.sup.68Asn.sup.69Thr.sup.71 EPO; Val.sup.87Asn.sup.88Thr.sup.90 EPO; Ser.sup.87Asn.sup.88Thr.sup.90 EPO; Ser.sup.87Asn.sup.88Gly.sup.89Thr.sup.90 EPO; Ser.sup.87Asn.sup.88Thr.sup.90Thr.sup.92 EPO; Ser.sup.87Asn.sup.88Thr.sup.90Ala.sup.162 EPO; Asn.sup.69Thr.sup.71Ser.sup.87Asn.sup.88Thr.sup.90 EPO; Asn.sup.89Ile.sup.90Thr.sup.91 EPO; Ser.sup.87Asn.sup.89Ile.sup.90Thr.sup.91 EPO; Asn.sup.136Thr.sup.138 EPO: Asn.sup.138Thr.sup.140 EPO; Thr.sup.123 EPO; Thr.sup.125 EPO; and Pro.sup.124Thr.sup.125 EPO.

23. An analog of human erythropoietin comprising the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO: 26 except for the amino acid changes Asn.sup.30Thr.sup.32Val.sup.87Asn.sup.88Thr.sup.90 EPO.

24. An analog of human erythropoietin comprising a fusion of a polypeptide fragment to the carboxy terminal end of human erythropoietin wherein the polypeptide fragment includes at least one glycosylation site having a carbohydrate chain attached thereto and wherein human erythropoietin comprises the amino acid sequence from residues 1 165 or 1 166 as shown in SEQ ID NO:26.

25. The analog of claim 24 wherein the polypeptide fragment is derived from the carboxy terminal end of human chorionic gonadotropin.

26. The analog of claim 25 wherein the polypeptide fragment has the amino acid sequence Ser-Ser-Ser-Ser-Lys-Ala-Pro-Pro-Pro-Ser-Leu-Pro-Ser-Pro-Ser-Arg-Leu-Pro-G- ly-Pro-Ser-Asp-Thr-Pro-Ile-Leu-Pro-Gln (SEQ ID NO:25).

27. An analog of human erythropoietin having the in vivo biological activity of increasing hematocrit comprising an amino acid sequence which differs from the amino acid sequence of human erythropoietin from residues 1 165 or 1 166 as shown in SEQ ID NO:26 at least by having one or more additional glycosylation site(s) and having a carbohydrate chain attached to the additional site(s), wherein the analog is fused at its carboxy terminus to a polypeptide fragment having at least one glycosylation site with a carbohydrate chain attached thereto.

28. The analog of any of claims 10, 19, 22 or 23 fused at its carboxy terminus to a polypeptide fragment having at least one glycosylation site with a carbohydrate chain attached thereto.

29. The analog of claim 27 wherein the polypeptide fragment is fused to the carboxy terminal end of Ser.sup.87Asn.sup.88Thr.sup.90 EPO.

30. The analog of claim 27 wherein the polypeptide fragment is fused to the carboxy terminal end of Asn.sup.30Thr.sup.32Val.sup.87Asn.sup.88Thr.sup.90 EPO.

31. The analog of claim 27 wherein the polypeptide fragment is derived from the carboxy terminal end of human chorionic gonadotropin.

32. The analog of claim 27 wherein the polypeptide fragment has the amino acid sequence Ser-Ser-Ser-Ser-Lys-Ala-Pro-Pro-Pro-Ser-Leu-Pro-Ser-Pro-Ser-Arg-Leu-Pro-G- ly-Pro-Ser-Asp-Thr-Pro-Ile-Leu-Pro-Gln (SEQ ID NO:25).

33. An analog of human erythropoietin having the in vivo biological activity of increasing hematocrit comprising an amino acid sequence which differs from the amino acid sequence of human erythropoietin from residues 1 165 as shown in SEQ ID NO:26 at least by having a deletion of one or more glycoyslation site(s) to which carbohydrate chains are attached and an addition of one or more non-naturally occurring glycosylation sites to which carbohydrate chains are attached to the additional site(s).

34. The analog of claim 33 comprising deletion of any of the N-linked carbohydrate sites in human erythropoietin and addition of an N-linked carbohydrate site at position 88.

35. The analog of claim 33 selected from the group consisting of: Gln.sup.24Ser.sup.87Asn.sup.88Thr.sup.90 EPO; Gln.sup.38Ser.sup.87Asn.sup.88Thr.sup.90 EPO; and Gln.sup.83Ser.sup.87Asn.sup.88Thr.sup.90 EPO.

36. The analog of claims 10, 19, 22, 23, 24, 27 or 33 which is the product of expression of an exogenous DNA sequence.

37. A DNA sequence encoding an analog of human erythropoietin according to any of claims 10, 19, 22, 23, 24, 27 or 33.

38. A eucaryotic host cell transfected with a DNA sequence according to claim 37 in a manner allowing the host cell to express an analog of human erythropoietin.

39. A composition comprising an erythropoietin analog according to any of claims 10, 19, 22, 23, 24, 27 or 33 together with a pharmaceutically acceptable diluent, adjuvant or carrier.

40. A method of increasing hematocrit in a patient in need thereof comprising administering a therapeutically effective amount of the composition of claim 39.

Details for Patent 7,217,689

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Ferring Pharmaceuticals Inc. NOVAREL chorionic gonadotropin For Injection 017016 01/15/1974 ⤷  Try a Trial 2024-05-15
Ferring Pharmaceuticals Inc. NOVAREL chorionic gonadotropin For Injection 017016 12/27/1984 ⤷  Try a Trial 2024-05-15
Ferring Pharmaceuticals Inc. NOVAREL chorionic gonadotropin For Injection 017016 02/15/1985 ⤷  Try a Trial 2024-05-15
Ferring Pharmaceuticals Inc. NOVAREL chorionic gonadotropin For Injection 017016 02/16/1990 ⤷  Try a Trial 2024-05-15
Bel-mar Laboratories, Inc. CHORIONIC GONADOTROPIN chorionic gonadotropin Injection 017054 03/26/1974 ⤷  Try a Trial 2024-05-15
Fresenius Kabi Usa, Llc CHORIONIC GONADOTROPIN chorionic gonadotropin For Injection 017067 03/05/1973 ⤷  Try a Trial 2024-05-15
Amgen, Inc. ARANESP darbepoetin alpha Injection 103951 09/17/2001 ⤷  Try a Trial 2024-05-15
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

International Patent Family for US Patent 7,217,689

Country Patent Number Estimated Expiration
South Africa 946122 ⤷  Try a Trial
South Africa 908166 ⤷  Try a Trial
World Intellectual Property Organization (WIPO) 9505465 ⤷  Try a Trial
World Intellectual Property Organization (WIPO) 9105867 ⤷  Try a Trial
United States of America 5856298 ⤷  Try a Trial
Ukraine 49793 ⤷  Try a Trial
Slovakia 50295 ⤷  Try a Trial
>Country >Patent Number >Estimated Expiration

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