Compositions for modulating blood-brain barrier transport

• US 7,700,554 B2
• Filed: 10/13/2006
• Issued: 04/20/2010
• Est. Priority Date: 07/25/2001
• Status: Expired due to Fees

• Current Assignee: Horizon Orphan, LLC (Amgen Inc.)
• Original Assignee: Raptor Pharmaceuticals Inc. (Amgen Inc.)
• Inventors: Yang, Joseph, Beliveau, Richard, Demeule, Michel, Gabathuler, Reinhard, Kennard, Malcolm L.
• Primary Examiner(s): Kolker; Daniel E.
• Application Number:
  US11/580,497
• Publication Number:
  US 20070167365A1
• Time in Patent Office: 1,285 Days
• Field of Search: None
• US Class Current: 424/1.69
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/40 Transferrins, e.g. lactoferrins, ovotransferrins
• CPC Class Codes: A61K 47/644 Transferrin, e.g. a lactoferrin or ovotransferrin
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/40 against enzymes

Abstract

This invention provides conjugates of therapeutic or active agents with melanotransferrin or with other ligands of a melanotransferrin receptor, melanotransferrin receptor modulators, and related compositions and methods for modulating blood-brain barrier transport by providing methods of screening and selecting such conjugates, ligands, and modulators in vitro and in vivo, and methods of use of such conjugates, modulators and ligands in diagnosis and the treatment of diseases, including particularly diseases of the central nervous system or lysosomal storage diseases.

Claims

1. A sterile composition comprising (a) a conjugate comprising receptor associated protein (RAP) and a chemotherapeutic agent, and (b) a sterile pharmaceutically acceptable carrier wherein the chemotherapeutic agent is selected from the group consisting of an alkylating agent, an alkaloid, an anti-metabolite, and an antibiotic.

2. The composition of claim 1 wherein the chemotherapeutic agent is selected from the group consisting of mechlorethamine hydrochloride, cyclopho sphamide, ifosfamide, chlorambucil, melphalan, busulfan, thiotepa (triethylenethiophosphoramide), carmustine, lomustine, streptozocin, vincristine, vinblastine, paclitaxel, methotrexate, mercaptopurine, thioguanine, fluorouracil, cytarabine, azacitidine, dactinomycin, doxorubicin, daunorubicin, idarubicin, bleomycin, picamycin, mitomycin, hydroxyurea, procarbazine, dacarbazine, cisplatin, carboplatin, asparaginase, etoposide, amsarcrine, mitotane, and mitoxantrone.