NOVEL LIPOSOME COMPOSITIONS

• US 20110081404A1
• Filed: 09/27/2010
• Published: 04/07/2011
• Est. Priority Date: 03/10/2005
• Status: Active Grant

• Current Assignee: Mebiopharm Co., Ltd.
• Original Assignee: Mebiopharm Co., Ltd.
• Inventors: Fujisawa, Tadashi, Okada, Kazushi, Ibuki, Tadayuki, Kim, Donghyun
• Granted Patent: US 8,758,810 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present disclosure provides lipid-containing compositions, including targeted liposomes encapsulating drug, and pharmaceutical formulations thereof, as well as methods for the making and using the lipid-containing compositions, including the use of the targeted liposomes in the treatment of cancer and other diseases.

Claims

1-254. -254. (canceled)

255. A targeted liposome comprising one or more-phosphatidylcholines, an N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, an encapsulated drug, and at least one additional lipid, which is cholesterol,

wherein the targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine comprises transferrin linked to a second N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine; and

wherein

the N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,

256. The targeted liposome of claim 255, wherein R¹, R², R⁵ and R⁶ are acyl groups selected from oleoyl group and palmitoyl group.

257. The targeted liposome of claim 255, wherein R¹, R², R⁵ and R⁶ are palmitoyl group.

258. The targeted liposome of claim 255, wherein the phosphatidylcholine includes a moiety of a saturated fatty acid.

259. The targeted liposome according to claim 255, wherein the transferrin is in a holo-form but not in an apo-form.

260. The targeted liposome according to claim 255, wherein the mean diameter of the liposome is from about 50 nm to about 250 nm.

261. The targeted liposome of claim 255, wherein R¹, R², R⁵ and R⁶ are oleoyl or palmitoyl, and m and p are 3.

262. The targeted liposome of claim 255, wherein the one or more phosphatidylcholines is DPPC.

263. The targeted liposome of claim 255, wherein m and p are each, independently, an integer from 2 to 4.

264. The targeted liposome of claim 255, wherein m and p are equal and are an integer from 2 to 4.

265. The targeted liposome of claim 264, wherein m and p are equal and are 3.

266. The targeted liposome of claim 255, wherein R¹, R², R⁵ and R⁶ are the same.

267. The targeted liposome according to claim 255, wherein the drug is an anticancer agent.

268. The targeted liposome according to claim 255, wherein the drug is a cytotoxic drug.

269. The targeted liposome according to claim 255, wherein the drug is a topoisomerase I inhibitor.

270. The targeted liposome according to claim 269, wherein the topoisomerase I inhibitor is topotecan or irinotecan.

271. The targeted liposome according to claim 255, wherein the drug is a vinca alkaloid.

272. The targeted liposome according to claim 271, wherein the vinca alkaloid is vincristine, vinblastine, vinleurosine, vinrodisine, vinorelbine or vindesine.

273. The targeted liposome according to claim 255, wherein the drug is a nucleic acid.

274. The targeted liposome according to claim 273, wherein the nucleic acid is an antisense oligonucleotide or a ribozyme.

275. The targeted liposome according to claim 255, wherein the drug is a platinum compound.

276. The targeted liposome according to claim 275, wherein the platinum compound is biplatin, cisplatin, carboplatin, ormaplatin, oxaliplatin, zeniplatin, enloplatin, lobaplatin or spiroplatin.

277. The targeted liposome according to claim 275, wherein the platinum compound is oxaliplatin.

278. The targeted liposome according to claim 255, wherein R¹, R², R⁵ and R⁶ are palmitoyl, m and p are 3, and the one or more phosphatidylcholines is DPPC.

279. The targeted liposome according to claim 255, wherein the drug is an alkylating agent.

280. The targeted liposome according to claim 255, wherein the drug is a taxane.

281. The targeted liposome according to claim 255, wherein the drug is a metabolic antagonist.

282. The targeted liposome according to claim 255, wherein the drug is an antitumour antibiotic.

283. The targeted liposome according to claim 255, wherein the drug is a hormone therapy drug.

284. The targeted liposome according to claim 255, wherein the drug is a molecular target drug.

285. The targeted liposome of claim 278, wherein the transferrin is in a holo-form.

286. The targeted liposome claim 255, wherein the liposome does not comprise a cationic lipid.

287. The targeted liposome of claim 255, wherein the liposome does not comprise an anionic lipid.

288. A pharmaceutical formulation comprising a targeted liposome according to claim 255 and one or more pharmaceutically acceptable carriers, excipients, diluents, stabilizers, or preservatives.

289. The targeted liposome of claim 255, wherein the targeted liposome contains from about 10 μ

g targeting ligand/mg lipid to about 25 μ

g targeting ligand/mg lipid.

290. The targeted liposome of claim 278, wherein the targeted liposome contains from about 10 μ

g targeting ligand/mg lipid to about 25 μ

g targeting ligand/mg lipid.

291. The targeted liposome of claim 255, wherein the total mol % of N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine and targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is from about 2 to about 12 mol % of total lipid content.

292. The targeted liposome of claim 278, wherein the total mol % of N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine and targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is from about 2 to about 12 mol % of total lipid content.

293. The targeted liposome of claim 255, wherein the total mol % of N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine and targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is from about 2 to about 10 mol % of total lipid content.

294. The targeted liposome of claim 278, wherein the total mol % of N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine and targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is from about 2 to about 10 mol % of total lipid content.

295. The targeted liposome of claim 255, wherein the mol % of the phosphatidylcholines is 40-65%, the mol % of the cholesterol is 30-60%, and the mol % of the total of the N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine plus targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is 2-12%.

296. The targeted liposome of claim 278, wherein the mol % of the phosphatidylcholines is 40-65%, the mol % of the cholesterol is 30-60%, and the mol % of the total of the N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine plus targeting factor-modified N-(ω

)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is 2-12%.

297. The targeted liposome according to claim 255, wherein R¹, R², R⁵ and R⁶ are oleoyl, and m and p are 3.

298. The targeted liposome according to claim 297, wherein the transferrin is in a holo-form.

299. The targeted liposome of claim 297, wherein the targeted liposome contains from about 10 μ

g targeting ligand/mg lipid to about 25 μ

g targeting ligand/mg lipid.

300. The targeted liposome of claim 297, wherein the mol % of the phosphatidylcholines is 30-70%.