Conjugates of glycosylated/galactosylated peptide, bifunctional linker, and nucleotidic monomers/polymers, and related compositions and method of use

• US 6,906,182 B2
• Filed: 11/30/2001
• Issued: 06/14/2005
• Est. Priority Date: 12/01/2000
• Status: Expired due to Fees

• Current Assignee: CELLective Dx Corporation
• Original Assignee: Cell Care Therapeutics, Johns Hopkins University
• Inventors: Ts'o, Paul O. P., Duff, Robert, Deamond, Scott
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): OWENS JR, HOWARD V
• Application Number:
  US09/998,497
• Publication Number:
  US 20030032584A1
• Time in Patent Office: 1,292 Days
• Field of Search: 514/8, 514/49, 514/50, 530/391.9, 530/391.7, 530/395, 530/397, 530/322, 536/23.1
• US Class Current: 530/391.9
• CPC Class Codes: A61K 47/6425 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

A conjugate of formula A-L-P, in which:

• • A represents a glycosylated/galactosylated peptide that binds to a cell-surface receptor,
  • L represents a bifunctional linker, which does not comprise a naturally occurring amino acid and is covalently bonded to A and P in a regiospecific manner, and
  • P represents a monomer, homopolymer or heteropolymer comprising at least one nucleotide or an analogue thereof, which inhibits the intracellular biosynthesis of nucleotides or nucleic acids in a sequence-independent manner,
  • wherein either or both of the covalent bond between A and L and the covalent bond between L and P can be cleaved intracellularly; a composition comprising such a conjugate; and a method of inhibiting abnormal cellular proliferation in a mammal; and a method of inhibiting replication of a virus in a mammal.

Claims

1. A compound having the formula

2. A method of treating hepatocellular carcinoma comprising administering to a patient in need thereof a composition compnsing the compound of claim 1.

3. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.