Immunoliposomes that optimize internationalization into target cells

• US 7,507,407 B2
• Filed: 10/11/2006
• Issued: 03/24/2009
• Est. Priority Date: 11/09/1994
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Hong, Keelung, Benz, Christopher C., Park, John W., Papahadjopoulos, Demetrios P., Kirpotin, Dmitri
• Primary Examiner(s): Yaen; Christopher H
• Application Number:
  US11/546,781
• Publication Number:
  US 20070031484A1
• Time in Patent Office: 895 Days
• Field of Search: None
• US Class Current: 424/143.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6913 the liposome being modified on its surface by an antibody
• CPC Class Codes: A61K 9/127 Liposomes
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

The present invention provides for immunoliposomes that optimizes internalization of a drug into target cells bearing a characteristic cell surface marker. The immunoliposomes comprise an Fab′ domain of an antibody that specifically binds the characteristic marker, an amphipathic vesicle-forming lipid, and a polyethylene glycol derivatized lipid. The invention also provides for growth-inhibiting immunoliposomes that lack growth-inhibiting therapeutic agents and yet are capable of inhibiting the growth and proliferation of target cells.

Claims

1. An immunoliposome that is internalized into a cell bearing a growth factor receptor on its cell surface, said immunoliposome comprising:

a hydrophilic polymer derivatized lipid;

a recombinantly produced antibody fragment specifically binding to the receptor on the cell surface said fragment attached to the hydrophilic polymer of the derivatized lipid; and

,

an amphipathic vesicle-forming lipid, said vesicle-forming lipid forming a liposome; and

, wherein when said immunoliposome is contacted with said cell bearing a growth factor receptor on its cell surface, said immunoliposome is internalized into the cell and where the growth factor receptor is selected from the group consisting of HER1 and HER2.

2. The immunoliposome of claim 1, wherein the antibody fragment is a Fab′

.

3. The immunoliposome of claim 1 wherein the antibody fragment is a humanized Fab′

domain of a monoclonal antibody.

4. The immunoliposome of claim 1, wherein said vesicle forming lipid is selected from the group consisting of a phospholipid, a glycolipid, a sphingolipid, and a sterol.

5. The immunoliposome of claim 1 wherein the hydrophilic polymer is polyethylene glycol.

6. An immunoliposome that is internalized into a cell bearing a HER 1 growth factor receptor on its cell surface, said immunoliposome comprising:

a hydrophilic polymer derivatized lipid;

a recombinantly produced antibody fragment specifically binding to the HER1 receptor on the cell surface said fragment attached to the hydrophilic polymer of the derivatized lipid; and

,

an amphipathic vesicle-forming lipid, said vesicle-forming lipid forming a liposome; and

, wherein when said immunoliposome is contacted with said cell bearing a growth factor receptor on its cell surface, said immunoliposome is internalized into the cell.

7. The immunoliposome of claim 6 wherein the antibody fragment is a Fab′

.

8. The immunoliposome of claim 6 wherein the antibody fragment is a humanized Fab′

domain of a monoclonal antibody.

9. The immunoliposome of claim 6 wherein said vesicle forming lipid is selected from the group consisting of a phospholipid, a glycolipid, a sphingolipid, and a sterol.

10. The immunoliposome of claim 6 wherein the hydrophilic polymer is polyethylene glycol.