Claims for Patent: 6,599,873

Summary for Patent: 6,599,873

Title:	Interleukin-1 inhibitors, compositions, and methods of treatment
Abstract:	Interleukin-1 inhibitors are provided. Compositions comprising an interleukin-1 inhibitor are provided. Methods of treating a patient comprising administering an interleukin-1 inhibitor are provided.
Inventor(s):	Sommer; Andreas (Concord, CA), Hannum; Charles H. (Boulder, CO), Eisenburg; Stephen P. (Boulder, CO), Thompson; Robert C. (Boulder, CO), Arend; William P. (Denver, CO), Joslin; Fenneke G. (Denver, CO)
Assignee:	Amgen Inc. (Thousand Oaks, CA) The Regents of the University of Colorado (Boulder, CO)
Application Number:	08/468,425
Patent Claims:	1. An interleukin-1 inhibitor (IL-1i), comprising a glycosylated or nonglycosylated polypeptide having interleukin-1 (IL-1) inhibitory activity and being free of other human protein, wherein said polypeptide is selected from the group consisting of: A) a polypeptide comprising all or an IL-1 inhibitory fragment of the amino acid sequence: 2. The IL-1i of claim 1, wherein the amino acid sequence of said polypeptide is at least about 95% homologous to the following amino acid sequence: 3. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 2. 4. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 2. 5. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 2. 6. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 2. 7. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 2. 8. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 2. 9. The IL-1i of claim 1, wherein the amino acid sequence of said polypeptide is at least about 90% homologous to the following amino acid sequence: 10. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 9. 11. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 9. 12. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 9. 13. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 9. 14. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 9. 15. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 9. 16. The IL-1i of claim 9, wherein the IL-1i is recombinantly made by a host cell not capable of glycosylation or a non-human host cell. 17. The IL-1i of claim 16, wherein said host cell is selected from a yeast cell, a mouse Ltk.sup.- cell, and a Chinese hamster ovary cell. 18. The IL-1i of claim 16, wherein said host cell is a prokaryotic cell. 19. The IL-1i of claim wherein said host cell is E. coli. 20. The IL-1i of claim 16, wherein said host cell is a eukaryotic cell. 21. The IL-1i of claim 20, wherein said host cell is a mammalian cell. 22. The IL-1i of claim 20, wherein said host cell is a Chinese hamster ovary cell. 23. The IL-1i of claim 9, wherein said IL-1i is glycosylated. 24. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 23. 25. The IL-1i of claim 9, wherein said IL-1i is nonglycosylated. 26. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 25. 27. The IL-1i of claim 9, wherein (U) is nothing. 28. The IL-1i of claim 9, wherein (U) is M. 29. The IL-1i of claim 1, wherein said IL-1i is a polypeptide comprising all or an IL-1 inhibitory fragment of the amino acid sequence: 30. The IL-1i of claim 21, wherein (X) is R. 31. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 30. 32. The IL-1i of claim 30, wherein said polypeptide inhibits IL-1 induced PGE.sub.2 production. 33. The IL-1i of claim 29, which comprises the following amino acid sequence: 34. The IL-1i of claim 33, wherein (X) is R. 35. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 30. 36. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 34. 37. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 34. 38. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 34. 39. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 34. 40. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 34. 41. The IL-1i of claim 34, wherein (U) is M. 42. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation. a therapeutically effective amount of the IL-1i of claim 41. 43. The IL-1i of claim 34, wherein (U) is nothing. 44. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 43. 45. The IL-1i of claim 34, wherein the IL-1i is recombinantly made by a host cell not capable of glycosylation or a non-human host cell. 46. The IL-1i of claim 45, wherein said host cell is selected from a yeast cell, a mouse Ltk.sup.- cell, and a Chinese hamster ovary cell. 47. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation a therapeutically effective amount of the IL-1i of claim 46. 48. The IL-1i of claim 46, wherein said host cell is a mouse Ltk.sup.- cell. 49. The IL-1i of claim 45, wherein said host cell is a prokaryotic cell. 50. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 49. 51. The IL-1i of claim 49, wherein said host cell is E. coli. 52. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically, effective amount of the IL-1i of claim 51. 53. The IL-1i of claim 45, wherein said host cell is a eukaryotic cell. 54. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 53. 55. The IL-1i of claim 53, wherein said host cell is a mammalian cell. 56. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 55. 57. The IL-1i of claim 53, wherein said host cell is a Chinese hamster ovary cell. 58. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 57. 59. The IL-1i of claim 34 having a purity of at least about 90%. 60. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 59. 61. The IL-1i of claim 34 having a purity of at least about 95%. 62. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 61. 63. The IL-1i of claim 34, wherein said IL-1i is glycosylated. 64. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 63. 65. The IL-1i of claim 34, wherein said IL-1i is nonglycosylated. 66. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 65. 67. The pharmaceutical composition of any of claims 42 or 64, further comprising a collagenase inhibitor. 68. The IL-1i of claim 34, wherein said IL-1i is derived from a host cell comprising a recombinant DNA molecule comprising a sequence encoding said IL-1i. 69. The IL-1i of claim 68, further comprising an N-terminal secretion leader sequence. 70. The IL-1i of claim 69, wherein the leader sequence comprises all or part of the following amino acid sequence: 71. The IL-1i of claim 34, which consists of the following amino acid sequence, 72. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 71. 73. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 71. 74. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 71. 75. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 71. 76. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 71. 77. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 71. 78. The IL-1i of claim 71, wherein (U) is M. 79. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 78. 80. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 78. 81. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 78. 82. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 78. 83. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 78. 84. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 76. 85. The IL-1i of claim 78, wherein said IL-1i is nonglycosylated. 86. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 85. 87. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 85. 88. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 85. 89. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 85. 90. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 85. 91. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 85. 92. The IL-1i of claim 85, wherein the IL-1i is recombinantly made by an E. coli host cell. 93. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 92. 94. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 92. 95. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 92. 96. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 92. 97. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 92. 98. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 92. 99. The IL-1i of claim 92 having a purity of at least about 90%. 100. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 99. 101. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 99. 102. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 99. 103. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 99. 104. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 99. 105. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 99. 106. The IL-1i of claim 92 having a purity of at least about 95%. 107. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 106. 108. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 106. 109. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 106. 110. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 106. 111. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 106. 112. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 106. 113. The IL-1i of claim 71 wherein the IL-1i is recombinantly made by a Chinese hamster ovary host cell. 114. The IL-1i of claim 71 having a purity of at least about 90%. 115. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 114. 116. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 114. 117. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 114. 118. A method of treating a patient having osteoarthritis comprising administering to the patent a therapeutically effective amount of an IL-1 inhibitor according to claim 114. 119. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 114. 120. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 114. 121. The IL-1i of claim 114, wherein said IL-1i is glycosylated. 122. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 121. 123. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 121. 124. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 121. 125. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 121. 126. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 121. 127. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative coitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 121. 128. The IL-1i of claim 71 having a purity of at least about 95%. 129. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 128. 130. A method of treating a patient having arthritis comprising administering to the patent a therapeutically effective amount of an IL-1 inhibitor according to claim 128. 131. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 128. 132. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 128. 133. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering toe patient a therapeutically effective amount of an IL-1 inhibitor according to claim 128. 134. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 128. 135. The IL-1i of claim 71, wherein the IL-1i is recombinantly made by a eukaryotic host cell. 136. The IL-1i of claim 128, wherein said IL-1i is glycosylated. 137. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 136. 138. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 136. 139. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 136. 140. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 136. 141. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 136. 142. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 136. 143. The IL-1i of claim 128, wherein the IL-1i is recombinantly made by a mammalian host cell. 144. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 143. 145. The IL-1i of claim 128, wherein the IL-1i is recombinantly made by a prokaryotic host cell. 146. An interleukin-1 inhibitor (IL-1i), comprising a glycosylated or nonglycosylated polypeptide having interleukin-1 (IL-1) inhibitory activity, wherein said polypeptide is produced by a non-human host cell comprising a recombinant DNA molecule comprising a sequence encoding said polypeptide, and wherein said polypeptide is selected from the group consisting of: A) a polypeptide comprising all or an IL-1 inhibitory fragment of the amino acid sequence: 147. The IL-1i of claim 146 wherein said polypeptide comprises an N-terminal amino acid sequence as follows: 148. The IL-1i of claim 146 wherein said polypeptide comprises the following amino acid sequence: 149. The IL-1i of claim 146 wherein said polypeptide comprises the following amino acid sequence: 150. The IL-1i of claim 146 wherein said polypeptide comprises the following amino acid sequence: 151. The IL-1i of claim 146 wherein said polypeptide comprises the following amino acid sequence: 152. The IL-1i of claim 146 wherein said polypeptide comprises the following amino acid sequence 153. The IL-1i of claim 146 wherein said polypeptide comprises the following amino acid sequence: 154. The IL-1i of claim 146, wherein the amino acid sequence of said polypeptide is at least about 95% homologous to the following amino acid sequence: 155. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 154. 156. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 154. 157. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 154. 158. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 154. 159. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 154. 160. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 154. 161. The IL-1i of claim 146, wherein the amino acid sequence of said polypeptide is at least about 90% homologous to the following amino acid sequence: 162. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 161. 163. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 161. 164. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 161. 165. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 161. 166. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 161. 167. A method of treating a patient having at least one of the Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 161. 168. The IL-1i of claim 161, wherein said host cell is selected from a yeast cell, a mouse Ltk.sup.- cell, and a Chinese hamster ovary cell. 169. The IL-1i of claim 161, wherein said host cell is a prokaryotic cell. 170. The IL-1i of claim 169, wherein said host cell is E. coli. 171. The IL1i of claim 161, wherein said host cell is a eukaryotic cell. 172. The IL-1i of claim 171, wherein said host cell is a mammalian cell. 173. The IL-1i of claim 174, wherein said host cell is a Chinese hamster ovary cell. 174. The IL-1i of claim 161, wherein said IL-1i is glycosylated. 175. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 174. 176. The IL-1i of claim 161, wherein said IL-1i is nonglycosylated. 177. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 176. 178. The IL-1i of claim 161, wherein (U) is nothing. 179. The IL-1i of claim 161, wherein (U) is M. 180. The IL-1i of claim 161, further comprising an N-terminal secretion leader sequence. 181. The IL-1i of claim 180, wherein the leader sequence comprises all or part of the following amino acid sequence: 182. The IL-1i of claim 146, wherein said IL-1i is a polypeptide comprising all or an IL-1 inhibitory fragment of the amino acid sequence: 183. The IL-1i of claim 183, wherein (X) is R. 184. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 183. 185. The IL-1i of claim 183, wherein said polypeptide inhibits IL-1 induced PGE.sub.2 production. 186. The IL-1i of claim 182, which comprises the following amino acid sequence: 187. The IL-1i of claim 186, wherein (X) is R. 188. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 187. 189. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 187. 190. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 187. 191. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 187. 192. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 187. 193. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 187. 194. The IL-1i of claim 187, wherein (U) is M. 195. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 194. 196. The IL-1i of claim 187, wherein (U) is nothing. 197. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 196. 198. The IL-1i of claim 187, wherein said host cell is selected from a yeast cell, a mouse Ltk.sup.- cell, and a Chinese hamster ovary cell. 199. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 198. 200. The IL-1i of claim 198, wherein said host cell is a mouse Ltk.sup.- cell. 201. The IL-1i of claim 187, wherein said host cell is a prokaryotic cell. 202. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 201. 203. The IL-1i of claim 201, wherein said host cell is E. coli. 204. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 203. 205. The IL-1i of claim 187, wherein said host cell is a eukaryotic cell. 206. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 205. 207. The IL-1i of claim 205, wherein said host cell is a mammalian cell. 208. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 207. 209. The IL-1i of claim 205, wherein said host cell is a Chinese hamster ovary cell. 210. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 209. 211. The IL-1i of claim 187 having a purity of at least about 90%. 212. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation. a therapeutically effective amount of the IL-1i of claim 211. 213. The IL-1i of claim 187 having a purity of at least about 95%. 214. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 213. 215. The pharmaceutical composition of any of claims 175 or 214, further comprising a collagenase inhibitor. 216. The IL-1i of claim 187, wherein said IL-1i is glycosylated. 217. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 216. 218. The IL-1i of claim 187, wherein said IL-1i is nonglycosylated. 219. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 218. 220. The IL-1i of claim 187, which consists of the following amino acid sequence: 221. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 220. 222. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 220. 223. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 220. 224. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 220. 225. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 220. 226. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 220. 227. The IL-1i of claim 187, wherein (U) is M. 228. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 227. 229. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 227. 230. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 227. 231. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 227. 232. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 227. 233. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 227. 234. The IL-1i of claim 227, wherein said IL-1i is nonglycosylated. 235. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 234. 236. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 234. 237. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 234. 238. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 234. 239. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 234. 240. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 234. 241. The IL-1i of claim 234, wherein the IL-1i is recombinantly made by an E. coli host cell. 242. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 241. 243. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 241. 244. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 241. 245. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 241. 246. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 241. 247. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 241. 248. The IL-1i of claim 241 having a purity of at least about 90%. 249. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 248. 250. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 248. 251. A method of treating a patient having rheumatoid arthritis comprising administering to the payment a therapeutically effective amount of an IL-1 inhibitor according to claim 248. 252. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 248. 253. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 248. 254. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 248. 255. The IL-1i of claim 241 having a purity of at least about 95%. 256. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 255. 257. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 255. 258. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 255. 259. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 255. 260. A method of treating a patient to reduce an adverse effect of IL-1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 255. 261. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 255. 262. The IL-1i of claim 220, wherein the IL-1i is recombinantly made by a Chinese hamster ovary cell. 263. The IL-1i of claim 220 having a purity of at least about 90%. 264. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 263. 265. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 263. 266. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 263. 267. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 263. 268. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 263. 269. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 263. 270. The IL-1i of claim 263, wherein said IL-1i is glycosylated. 271. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 270. 272. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 270. 273. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 270. 274. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 270. 275. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 270. 276. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 270. 277. The IL-1i of claim 220 having a purity of at least about 95%. 278. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 277. 279. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 277. 280. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 277. 281. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 277. 282. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 277. 283. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according lo claim 277. 284. The IL-1i of claim 277, wherein the IL-1i is recombinantly made by a eukaryotic host cell. 285. The IL-1i of claim 277, wherein said IL-1i is glycosylated. 286. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 285. 287. A method of treating a patient having arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 285. 288. A method of treating a patient having rheumatoid arthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 285. 289. A method of treating a patient having osteoarthritis comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 285. 290. A method of treating a patient to reduce an adverse effect of IL1 comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 285. 291. A method of treating a patient having at least one of the following: Crohn's disease, ulcerative colitus, glomerulonephritis, or leukemia, comprising administering to the patient a therapeutically effective amount of an IL-1 inhibitor according to claim 285. 292. The IL-1i of claim 277, wherein the IL-1i is recombinantly made by a mammalian host cell. 293. A pharmaceutical composition comprising, in a pharmaceutically acceptable preparation, a therapeutically effective amount of the IL-1i of claim 292. 294. The IL-1i of claim 277, wherein the IL-1i is recombinantly made by a prokaryotic host cell. 295. A method of any one of claims 4-6, 11-13, 36-38, 73-75, 80-82, 87-89, 94-96, 101-103, 108-110, 116-118, 123-125, 130-132, and 138-140, further comprising administering to the patient a therapeutically effective amount of a collagenase inhibitor. 296. A method of any one of claims 156-158, 163-165, 189-191, 222-224, 229-231, 236-238, 243-245, 250-252, 257-259, 265-267, 272-274, 279-281, and 287-289, further comprising administering to the patient a therapeutically effective amount of a collagenase inhibitor.

Details for Patent 6,599,873

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	June 04, 1965		2020-07-29
Swedish Orphan Biovitrum Ab (publ)	KINERET	anakinra	Injection	103950	November 14, 2001		2020-07-29

International Patent Family for US Patent 6,599,873

Country	Patent Number	Estimated Expiration
South Africa	911981
South Africa	905593
South Africa	894052
World Intellectual Property Organization (WIPO)	9534326