Immunoliposomes that optimize internalization into target cells

• US 7,135,177 B2
• Filed: 02/28/2001
• Issued: 11/14/2006
• 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., Kirpotin, Dmitri, Papahadjopoulos, Demetrois
• Primary Examiner(s): Yaen, Christopher
• Application Number:
  US09/797,544
• Publication Number:
  US 20010016196A1
• Time in Patent Office: 2,085 Days
• Field of Search: 424/178.1, 424/130.1, 424/450
• 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 HER2 growth factor receptor on its cell surface, said immunoliposome comprising:

a hydrophilic polymer derivatized lipid;

a recombinantly produced antibody fragment specifically binding to the HER2 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 HER2 growth factor receptor on its cell surface, said immunoliposome is internalized into the cell.

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 inmunoliposome of claim 1 wherein the hydrophilic polymer is polyethylene glycol.