ANTIBODIES AND IMMUNOCONJUGATES AND USES THEREFOR

• US 20110142859A1
• Filed: 11/04/2010
• Published: 06/16/2011
• Est. Priority Date: 05/30/2006
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: LIANG, WEI-CHING, WU, YAN, YU, SHANG-FAN, GRAY, ALANE M., EBENS, ALLEN J. JR.
• Granted Patent: US 8,226,945 B2
• Time in Patent Office: Days
• US Class Current: 424/178.1
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/68031 the drug being an auristatin
• CPC Class Codes: A61K 47/68033 the drug being a maytansine
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6855 the tumour determinant being from breast cancer cell
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Anti-CD22 antibodies and immunoconjugates thereof are provided. Methods of using anti-CD22 antibodies and immunoconjugates thereof are provided.

Claims

1. An antibody that binds to CD22, comprising:

(a) an HVR-L1 sequence of SEQ ID NO;

10;

(b) an HVR-H1 sequence of SEQ ID NO;

2;

(c) an HVR-H2 sequence of SEQ ID NO;

4;

(d) an HVR-H3 sequence of SEQ ID NO;

6;

(e) an HVR-L2 sequence of SEQ ID NO;

12; and

(f) an HVR-L3 sequence of SEQ ID NO;

14.

13. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain of SEQ ID NO:

16.

15. The antibody of claim 1, wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO:

18.

19. The antibody of claim 13, further comprising a light chain variable domain sequence of SEQ ID NO:

18.

20. The antibody of claim 1, wherein the antibody comprises a heavy chain sequence of SEQ ID NO:

88.

21. The antibody of claim 1, wherein the antibody comprises a light chain sequence of SEQ ID NO:

87.

22. The antibody of claim 1, wherein the antibody comprises a heavy chain sequence of SEQ ID NO:

88 and a light chain sequence of SEQ ID NO;

87.

28. The antibody of claim 1, wherein the antibody is humanized.

60. The antibody of claim 1, wherein the antibody is a monoclonal antibody.

76. An immunoconjugate comprising an antibody of claim 1 covalently attached to a cytotoxic agent.

78. The immunoconjugate of claim 76, wherein the cytotoxic agent is selected from a toxin, a chemotherapeutic agent, a drug moiety, an antibiotic, a radioactive isotope, and a nucleolytic enzyme.

79. The immunoconjugate of claim 78, the immunoconjugate having the formula Ab-(L-D)_p, wherein:

(a) Ab is the antibody of claim 1 ;

(b) L is a linker;

(c) D is a drug moiety; and

(d) p ranges from about 1 to 8.

80. The immunoconjugate of claim 79, wherein L is selected from 6-maleimidocaproyl (MC), maleimidopropanoyl (MP), valine-citrulline (val-cit), alanine-phenylalanine (ala-phe), p-aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2-pyridylthio) pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate (SMCC), and N-Succinimidyl (4-iodo-acetyl)aminobenzoate (SIAB).

81. The immunoconjugate of claim 79, wherein D is selected from an auristatin and dolostantin.

82. The immunoconjugate of claim 81, wherein D is a drug moiety of formula D_E or D_F:

83. The immunoconjugate of claim 76, having in vitro or in vivo cell killing activity.

84. The immunoconjugate of claim 79, wherein the linker is attached to the antibody through a thiol group on the antibody.

85. The immunoconjugate of claim 79, wherein the linker is cleavable by a protease.

86. The immunoconjugate of claim 80, wherein the linker comprises a val-cit dipeptide.

87. The immunoconjugate of claim 79, wherein the linker comprises a p-aminobenzyl unit.

88. The immunoconjugate of claim 80, wherein the linker comprises 6-maleimidocaproyl.

89. The immunoconjugate of claim 82, wherein the drug is selected from MMAE and MMAF.

90. The immunoconjugate of claim 89, wherein the drug is MMAE.

91. The immunoconjugate of claim 89, wherein the drug is MMAF.

2. (canceled)

3. (canceled)

4. (canceled)

5. (canceled)

6. (canceled)

7. (canceled)

8. (canceled)

9. (canceled)

10. (canceled)

11. (canceled)

12. (canceled)

14. (canceled)

16. (canceled)

17. (canceled)

18. (canceled)

23. (canceled)

24. (canceled)

25. (canceled)

26. (canceled)

27. (canceled)

29. (canceled)

30. (canceled)

31. (canceled)

32. (canceled)

33. (canceled)

34. (canceled)

35. (canceled)

36. (canceled)

37. (canceled)

38. (canceled)

39. (canceled)

40. (canceled)

41. (canceled)

42. (canceled)

43. (canceled)

44. (canceled)

45. (canceled)

46. (canceled)

47. (canceled)

48. (canceled)

49. (canceled)

50. (canceled)

51. (canceled)

52. (canceled)

53. (canceled)

54. (canceled)

55. (canceled)

56. (canceled)

57. (canceled)

58. (canceled)

59. (canceled)

61. (canceled)

62. (canceled)

63. (canceled)

64. (canceled)

65. (canceled)

66. (canceled)

67. (canceled)

68. (canceled)

69. (canceled)

70. (canceled)

71. (canceled)

72. (canceled)

73. (canceled)

74. (canceled)

75. (canceled)

77. (canceled)

92. (canceled)

93. (canceled)

94. (canceled)

95. (canceled)

96. (canceled)

97. (canceled)

98. (canceled)

99. (canceled)

100. (canceled)

101. (canceled)

102. (canceled)

103. (canceled)

104. (canceled)

105. (canceled)

106. (canceled)

107. (canceled)

108. (canceled)

109. (canceled)

110. (canceled)

111. (canceled)

112. (canceled)

113. (canceled)

114. (canceled)

115. (canceled)

116. (canceled)

117. (canceled)

118. (canceled)

119. (canceled)

120. (canceled)

121. (canceled)

122. (canceled)

123. (canceled)

124. (canceled)

125. (canceled)

126. (canceled)

127. (canceled)

128. (canceled)

129. (canceled)

130. (canceled)

131. (canceled)

132. (canceled)

133. (canceled)

134. (canceled)

135. (canceled)

136. (canceled)

137. (canceled)

138. (canceled)

139. (canceled)

140. (canceled)

141. (canceled)

142. (canceled)

143. (canceled)

144. (canceled)

145. (canceled)

146. (canceled)

147. (canceled)

148. (canceled)

149. (canceled)

150. (canceled)

151. (canceled)

152. (canceled)

153. (canceled)

154. (canceled)

155. (canceled)

156. (canceled)

157. (canceled)

158. (canceled)

159. (canceled)

160. (canceled)

161. (canceled)

162. (canceled)

163. (canceled)

164. (canceled)

165. (canceled)

166. (canceled)

167. (canceled)

168. (canceled)

169. (canceled)

170. (canceled)

171. (canceled)

172. (canceled)

173. (canceled)

174. (canceled)

175. (canceled)

176. (canceled)

177. (canceled)

178. (canceled)

179. (canceled)

180. (canceled)

181. (canceled)

182. (canceled)

183. (canceled)

184. (canceled)

185. (canceled)

186. (canceled)

187. (canceled)

188. (canceled)

189. (canceled)

190. (canceled)

191. (canceled)

192. (canceled)

193. (canceled)

194. (canceled)

195. (canceled)

196. (canceled)

197. (canceled)

198. (canceled)

199. (canceled)

200. (canceled)

201. (canceled)

202. (canceled)

203. (canceled)

204. (canceled)

205. (canceled)

206. (canceled)

207. (canceled)

208. (canceled)

209. (canceled)

210. (canceled)

211. (canceled)

212. (canceled)

213. (canceled)

214. (canceled)

215. (canceled)

216. (canceled)

217. (canceled)

218. (canceled)

219. (canceled)

220. (canceled)

221. (canceled)

222. (canceled)

223. (canceled)

224. (canceled)

225. (canceled)

226. (canceled)

227. (canceled)

228. (canceled)

229. (canceled)

230. (canceled)

231. (canceled)

232. (canceled)

233. (canceled)

234. (canceled)

235. (canceled)

236. (canceled)

237. (canceled)

238. (canceled)