Claims for Patent: RE36755

Summary for Patent: RE36755

Title:	DNA encoding tumor necrosis factor-.alpha. and -.beta. receptors
Abstract:	Tumor necrosis factor receptor DNAs and expression vectors encoding TNF receptors, and processes for producing TNF receptors as products of recombinant cell culture, are disclosed.
Inventor(s):	Smith; Craig A. (Seattle, WA), Goodwin; Raymond G. (Seattle, WA), Beckmann; M. Patricia (Poulsbo, WA)
Assignee:	Immunex Corporation (Seattle, WA)
Application Number:	09/144,502
Patent Claims:	1. An isolated DNA sequence selected from the group consisting of: (a) a DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of amino acids 1 to X of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino acid from 163 to 235; and (b) a DNA sequence capable of hybridization to the complement of the DNA sequence of (a) under moderately stringent conditions (50.degree. C., 2.times.SSC) and which encodes a polypeptide that is capable of binding to TNF and which is at least 88% identical to a polypeptide encoded by the DNA of (a)..]..[.2. An isolated DNA sequence selected from the group consisting off (a) a DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of amino acids 1 to X of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino acid from 163 to 235; and (b) a DNA sequence capable of hybridization to the complement of the DNA sequence of (a) under moderately stringent conditions (50.degree. C., 2.times.SSC) and which encodes TNF-R protein that is capable of binding greater than 0.1 nmoles TNF per nmole TNF-R and which is at least 88% identical to a polypeptide encoded by the DNA of (a)..]..[.3. An isolated DNA sequence selected from the group consisting of: (a) a DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of amino acids 1 to X of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino acid from 163 to 235; and (b) a DNA sequence capable of hybridization to the complement of the DNA sequence of (a) under moderately stringent conditions (50.degree. C., 2.times.SSC) and which encodes TNF-R protein that is capable of binding greater than 0.5 nmoles TNF per nmole TNF-R and which is at least 88% identical to a polypeptide encoded by the DNA of (a)..]..[.4. A recombinant expression vector comprising the DNA sequence according to claim 1..]..[.5. A recombinant expression vector comprising the DNA sequence according to claim 2..]..[.6. A recombinant expression vector comprising the DNA sequence according to claim 3..]..[.7. A host cell transformed or transfected with the vector according to claim 4..]..[.8. A host cell transformed or transfected with the vector according to claim 5..]..[.9. A host cell transformed or transfected with the vector according to claim 6..]..[.10. An isolated DNA sequence selected from the group consisting of: (a) a DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of amino acids 1 to X of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino acid from 163 to 235; and (b) a DNA sequence that encodes a polypeptide identical to the polypeptide encoded by the DNA of (a) except for modification(s) to the amino acid sequence selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; (iii) conservative amino acid substitutions; (iv) substitution or deletion of cysteine residues; and (v) combinations of modifications (i)-(iv); wherein such polypeptide is capable of binding TNF..]..[.11. An isolated DNA sequence selected from the group consisting of: (a) a DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of amino acids 1 to X of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino acid from 163 to 235; and (b) a DNA sequence that encodes a polypeptide identical to the polypeptide encoded by the DNA of (a) except for modification(s) to the amino acid sequence selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; (iii) conservative amino acid substitutions; (iv) substitution or deletion of cysteine residues; and (v) combinations of modifications (i)-(iv); which encoded polypeptide is capable of binding greater than 0.1 moles TNF per nmole of such polypeptide..]..[.12. An isolated DNA sequence selected from the group consisting of: (a) a DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of amino acids 1 to X of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino acid from 163 to 235; and (b) a DNA sequence that encodes a polypeptide identical to the polypeptide encoded by the DNA of (a) except for modification(s) to the amino acid sequence selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; (iii) conservative amino acid substitutions; (iv) substitution or deletion of cysteine residues; and (v) combinations of modifications (i)-(iv); which encoded polypeptide is capable of binding greater than 0.5 moles TNF per nmole of such polypeptide..]..[.13. A recombinant expression vector comprising the DNA according to any of claims 10, 11 or 12..]..[.14. A host cell transformed or transfected with the vector according to claim 13..]..[.15. A DNA sequence that encodes a polypeptide having the amino acid sequence selected from the group consisting of (a) amino acids 1-235 of FIG. 2A; and (b) a DNA sequence capable of hybridization to the DNA sequence of (a) under moderately stringent conditions (50.degree. C., 2.times.SSC) and which encodes a polypeptide that is capable of binding to TNF and which is at least 88% identical to a polypeptide encoded by the DNA of (a)..]..[.16. A recombinant expression vector comprising the DNA sequence according to claim 15..]..[.17. A host cell transformed or transfected with the vector according to claim 16..]..Iadd.18. An isolated DNA molecule encoding a protein comprising a sequence of amino acids selected from the group consisting of amino acids 1-163 of SEQ ID NO:1 and amino acids 1-233 of SEQ ID NO:3, wherein said protein is capable of binding TNF. .Iaddend..Iadd.19. The isolated DNA molecule according to claim 18, wherein said protein comprises amino acids 1-163 of SEQ ID NO:1. .Iaddend..Iadd.20. The isolated DNA molecule according to claim 18, wherein said protein comprises amino acids 1-185 of SEQ ID NO:1. .Iaddend..Iadd.21. The isolated DNA molecule according to claim 18, wherein said protein comprises amino acids 1-235 of SEQ ID NO:1. .Iaddend..Iadd.22. An isolated DNA molecule encoding a protein selected from the group consisting of: (a) a polypeptide having a sequence of amino acids comprising amino acids 1-163 of SEQ ID NO:1; (b) a polypeptide having a sequence of amino acids comprising amino acids 1-233 of SEQ ID NO:3; and (c) a polypeptide identical to the polypeptides of (a) or (b) except for one or more modification(s) to the sequence of amino acids selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; and (iii) substitution or deletion of cysteine residues, wherein said protein is capable of binding TNF. .Iaddend..Iadd.23. A recombinant expression vector comprising the DNA molecule according to claim 18, 19, 20, 21 or 22. .Iaddend..Iadd.24. A host cell transformed or transfected with the recombinant expression vector according to claim 23. .Iaddend..Iadd.25. The host cell of claim 24, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.26. The host cell of claim 25, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.27. The host cell of claim 26, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.28. A process for producing a protein capable of binding TNF, said process comprising culturing a host cell of claim 24 under conditions suitable to effect expression of said protein. .Iaddend..Iadd.29. The process of claim 28, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.30. The process of claim 29, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.31. The process of claim 30, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.32. An isolated DNA molecule encoding a soluble TNF receptor protein comprising a sequence of amino acids selected from the group consisting of from about amino acid 1 to about amino acid 163 of SEQ ID NO:1 and from about amino acid 1 to about amino acid 233 of SEQ ID NO:3, wherein said soluble TNF receptor protein is capable of binding TNF protein. .Iaddend..Iadd.33. The isolated DNA molecule according to claim 32, wherein said soluble TNF receptor protein comprises from about amino acid 1 to about amino acid 163 of SEQ ID NO:1. .Iaddend..Iadd.34. The isolated DNA molecule according to claim 32, wherein said soluble TNF receptor protein comprises from about amino acid 1 to about amino acid 185 of SEQ ID NO:1. .Iaddend..Iadd.35. The isolated DNA molecule according to claim 32, wherein said TNF soluble receptor protein comprises from about amino acid 1 to about amino acid 235 of SEQ ID NO:1. .Iaddend..Iadd.36. An isolated DNA molecule encoding a soluble TNF receptor protein selected from the group consisting of: (a) a TNF receptor polypeptide having a sequence of amino acids comprising from about amino acid 1 to about amino acid 163 of SEQ ID NO:1; (b) a TNF receptor polypeptide having a sequence of amino acids comprising from about amino acid 1 to about amino acid 233 of SEQ ID NO:3; and (c) a TNF receptor polypeptide identical to the TNF receptor polypeptides of (a) or (b) except for one or more modification(s) to the sequence of amino acids selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; and (iii) substitution or deletion of cysteine residues, wherein said soluble TNF receptor protein is capable of binding TNF. .Iaddend..Iadd.37. A recombinant expression vector comprising the DNA molecule according to claim 32, 33, 34, 35 or 36. .Iaddend..Iadd.38. A host cell transformed or transfected with the recombinant expression vector according to claim 37. .Iaddend..Iadd.39. The host cell of claim 38, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.40. The host cell of claim 39, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.41. The host cell of claim 40, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.42. A process for producing a protein capable of binding TNF, said process comprising culturing a host cell of claim 38 under conditions suitable to effect expression of said protein. .Iaddend..Iadd.43. The process of claim 42, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.44. The process of claim 43, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.45. The process of claim 44, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.46. An isolated DNA molecule encoding a soluble TNF receptor protein comprising a sequence of amino acids selected from the group consisting of from amino acid 1 to amino acid 163 of SEQ ID NO:1 and from amino acid 1 to amino acid 233 of SEQ ID NO:3, wherein said soluble TNF receptor protein is capable of binding TNF protein. .Iaddend..Iadd.47. The isolated DNA molecule according to claim 46, wherein said soluble TNF receptor protein comprises from amino acid 1 to amino acid 163 of SEQ ID NO:1. .Iaddend..Iadd.48. The isolated DNA molecule according to claim 46, wherein said soluble TNF receptor protein comprises from amino acid 1 to amino acid 185 of SEQ ID NO:1. .Iaddend..Iadd.49. The isolated DNA molecule according to claim 46, wherein said soluble TNF receptor protein comprises from amino acid 1 to amino acid 235 of SEQ ID NO:1. .Iaddend..Iadd.50. An isolated DNA molecule encoding a soluble TNF receptor protein selected from the group consisting of: (a) a TNF receptor polypeptide having a sequence of amino acids comprising from amino acid 1 to amino acid 163 of SEQ ID NO:1; (b) a TNF receptor polypeptide having a sequence of amino acids comprising from amino acid 1 to amino acid 233 of SEQ ID NO:3; and (c) a TNF receptor polypeptide identical to the TNF receptor polypeptides of (a) or (b) except for one or more modification(s) to the sequence of amino acids selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; and (iii) substitution or deletion of cysteine residues, wherein said soluble TNF receptor protein is capable of binding TNF. .Iaddend..Iadd.51. A recombinant expression vector comprising the DNA molecule according to claim 46, 47, 48, 49 or 50. .Iaddend..Iadd.52. A host cell transformed or transfected with the recombinant expression vector according to claim 51. .Iaddend..Iadd.53. The host cell of claim 52, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.54. The host cell of claim 53, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.55. The host cell of claim 54, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.56. A process for producing a protein capable of binding TNF, said process comprising culturing a host cell of claim 52 under conditions suitable to effect expression of said protein. .Iaddend..Iadd.57. The process of claim 56, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.58. The process of claim 57, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.59. The process of claim 58, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.60. An isolated DNA molecule encoding a protein comprising a sequence of amino acids selected from the group consisting of amino acids 1-163 of SEQ ID NO:1 and amino acids 1-233 of SEQ ID NO:3, wherein said protein lacks amino acids 236-265 of SEQ ID NO:1 and amino acids 234-265 of SEQ ID NO:3, respectively, and wherein said protein is capable of binding TNF. .Iaddend..Iadd.61. The isolated DNA molecule according to claim 60, wherein said protein comprises amino acids 1-163 of SEQ ID NO:1. .Iaddend..Iadd.62. The isolated DNA molecule according to claim 60, wherein said protein comprises amino acids 1-185 of SEQ ID NO:1. .Iaddend..Iadd.63. The isolated DNA molecule according to claim 60, wherein said protein comprises amino acids 1-235 of SEQ ID NO:1. .Iaddend..Iadd.64. An isolated DNA molecule encoding a protein selected from the group consisting of: (a) a TNF receptor polypeptide having a sequence of amino acids comprising amino acids 1-163 of SEQ ID NO:1, wherein said polypeptide lacks amino acids 236-265 of SEQ ID NO:1; (b) a TNF receptor polypeptide having a sequence of amino acids comprising amino acids 1-233 of SEQ NO:3, wherein said polypeptide lacks amino acids 234-265 of SEQ ID NO:3; and (c) a TNF receptor polypeptide identical to the TNF receptor polypeptides of (a) or (b) except for one or more modification(s) to the sequence of amino acids selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; and (iii) substitution or deletion of cysteine residues, wherein said protein is capable of binding TNF. .Iaddend..Iadd.65. A recombinant expression vector comprising the DNA molecule according to claim 60, 61, 62, 63 or 64. .Iaddend..Iadd.66. A host cell transformed or transfected with the recombinant expression vector according to claim 65. .Iaddend..Iadd.67. The host cell of claim 66, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.68. The host cell of claim 67, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.69. The host cell of claim 68, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.70. A process for producing a protein capable of binding TNF, said process comprising culturing a host cell of claim 67 under conditions suitable to effect expression of said protein. .Iaddend..Iadd.71. The process of claim 70, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.72. The process of claim 71, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.73. The process of claim 72, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.74. An isolated DNA molecule encoding a protein comprising a sequence of amino acids selected from the group consisting of amino acids 1-163 of SEQ ID NO:1 and amino acids 1-233 of SEQ ID NO:3, wherein said protein lacks a functional transmembrane region, and wherein said protein is capable of binding TNF. .Iaddend..Iadd.75. The isolated DNA molecule according to claim 74, wherein said protein comprises amino acids 1-163 of SEQ ID NO:1. .Iaddend..Iadd.76. The isolated DNA molecule according to claim 74, wherein said protein comprises amino acids 1-185 of SEQ ID NO:1. .Iaddend..Iadd.77. The isolated DNA molecule according to claim 74, wherein said protein comprises amino acids 1-235 of SEQ ID NO:1. .Iaddend..Iadd.78. An isolated DNA molecule encoding a protein selected from the group consisting of: (a) a TNF receptor polypeptide having a sequence of amino acids comprising amino acids 1-163 of SEQ ID NO:1; (b) a TNF receptor polypeptide having a sequence of amino acids comprising amino acids 1-233 of SEQ ID NO:3; and (c) a TNF receptor polypeptide identical to the TNF receptor polypeptides of (a) or (b) except for one or more modification(s) to the sequence of amino acids selected from the group consisting of: (i) inactivated N-linked glycosylation sites; (ii) altered KEX2 protease cleavage sites; and (iii) substitution or deletion of cysteine residues, wherein said protein lacks a functional transmembrane region; and wherein said protein is capable of binding TNF. .Iaddend..Iadd.79. A recombinant expression vector comprising the DNA molecule according to claim 74, 75, 76, 77 or 78. .Iaddend..Iadd.80. A host cell transformed or transfected with the recombinant expression vector according to claim 79. .Iaddend..Iadd.81. The host cell of claim 80, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.82. The host cell of claim 81, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.83. The host cell of claim 82, wherein said mammalian cells are CHO cells. .Iaddend..Iadd.84. A process for producing a protein capable of binding TNF, said process comprising culturing a host cell of claim 80 under conditions suitable to effect expression of said protein. .Iaddend..Iadd.85. The process of claim 84, wherein said host cell is selected from the group consisting of microbial cells and mammalian cells. .Iaddend..Iadd.86. The process of claim 85, wherein said mammalian cells are selected from the group consisting of L cells, C127 cells, 3T3 cells, CHO cells, BHK cells and COS-7 cells. .Iaddend..Iadd.87. The process of claim 86, wherein said mammalian cells are CHO cells. .Iaddend.

Details for Patent RE36755

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	November 02, 1998		2009-09-05
Immunex Corporation	ENBREL	etanercept	For Injection	103795	May 27, 1999		2009-09-05
Immunex Corporation	ENBREL	etanercept	Injection	103795	September 27, 2004		2009-09-05

International Patent Family for US Patent RE36755

Country	Patent Number	Estimated Expiration
South Africa	907072
World Intellectual Property Organization (WIPO)	9406476
World Intellectual Property Organization (WIPO)	9319777