Liposome bonded with antibody and polyalkylene glycol

• US 20080014255A1
• Filed: 06/21/2007
• Published: 01/17/2008
• Est. Priority Date: 04/23/1999
• Status: Abandoned Application

• Current Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Original Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Inventors: Hosokawa, Saiko, Tagawa, Toshiaki
• Application Number:
  US11/812,804
• Publication Number:
  US 20080014255A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 47/6913 the liposome being modified on its surface by an antibody
• 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: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A liposome wherein a compound containing a polyalkylene glycol moiety is bonded through a thioether group and an antibody is bonded through a thioether group to a liposome comprising lipids whose partial component has maleimidated terminal, wherein an amount of the bonded compound and an amount of bonded antibody is 15 to 50 mole % and 0.1 to 2 mole %, respectively, based on one mole of the maleimidated lipid contained in the liposome. The liposome achieves both excellent blood retention and therapeutic effect.

Claims

1. A liposome comprising a bonded compound containing a polyalkylene glycol moiety bound to the liposome through thioether groups and a separately bonded antibody bound to the liposome through thioether groups, said liposome comprising lipids whose partial component has maleimidated terminal, and wherein an amount of the bonded compound is 15 to 30 mole % based on one mole of the maleimidated lipid, and an amount of the bonded antibody is 1.2 to 2 mg per 100 mg of total lipids that constitute the liposome, and said antibody comprising a GAH antibody.

2. The liposome according to claim 1, which is obtained by reacting a maleimide group of the maleimidated lipid with the compound containing a polyalkylene glycol moiety introduced with a thiol group.

3. The liposome according to claim 1, wherein the compound is bonded to a surface of the liposome.

4. The liposome according to claim 1, wherein the polyalkylene glycol is polyethylene glycol.

5. The liposome according to claim 4, wherein the compound has two polyethylene glycol groups.

6. The liposome according to claim 5, wherein each polyethylene glycol group has a molecular weight of 2,000 to 7,000 daltons.

7. The liposome according to claim 5, wherein each polyethylene glycol group has a molecular weight of about 5,000 daltons.

8. The liposome according to claim 1, which is a liposome obtained by reacting a liposome having a maleimide group and a sulfur-containing group deriving from the antibody to form a thioether bond.

9. A medicament composition for treatment of cancer comprising the liposome according to claim 1 and a medicament effective for treatment of cancer.

10. The medicament composition according to claim 9, wherein the cancer is stomach cancer or colon cancer.

11. A method for treatment of cancer which comprises administering to a patient the medicament composition according to claim 9.

12. The medicament composition according to claim 9 wherein the medicament comprises doxorubicin.