Cationized antibodies for delivery through the blood-brain barrier

• US 5,004,697 A
• Filed: 08/17/1987
• Issued: 04/02/1991
• Est. Priority Date: 08/17/1987
• Status: Expired due to Term

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc), William Pardridge
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc), University Incorporated
• Inventors: Pardridge, William M.
• Primary Examiner(s): Schain, Howard E.
• Assistant Examiner(s): Koh, Choon P.
• Application Number:
  US07/085,627
• Time in Patent Office: 1,324 Days
• Field of Search: 424/85.8, 530/391, 530/389, 436/548, 435/7
• US Class Current: 424/1.49
• 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: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

The rate of trancytosis of antibodies across the blood-brain barrier is increased by cationizing the antibodies to provide cationized antibodies having an isoelectric point of between about 8.0 to 11.0. The increased rates of transport across the blood-brain barrier makes such cationized antibodies useful for both neurodiagnostic and neuropharmaceutical purposes. Methods for preparing such cationized antibodies are disclosed.

Claims

1. In a diagnostic composition comprising one or more antibodies for administration to an individual for neurodiagnostic purposes, said antibodies having a relatively low transfer rate across the blood-brain barrier, wherein the improvement comprises cationizing said antibodies to provide cationized antibodies having an isoelectric point of between about 8.0 and 11.0, said cationized antibodies having increased rates of transfer across said blood-brain barrier.

2. A diagnostic composition according to claim 1, wherein said antibodies are monoclonal antibodies.

3. A diagnostic composition according to claim 2 wherein the isoelectric point of said cationized antibodies is between about 8.0 to 9.0.

4. A diagnostic composition according to claim 1 wherein said antibody is an antibody to an Alzheimer'"'"'s disease amyloid peptide.

5. A diagnostic composition according to claim 1 wherein said antibody is an antibody to one or more antigens present in GFAP protein.

6. In a neuropharmaceutical composition comprising one or more antibodies for administration to an individual for neurotherapeutic purposes, said antibodies having a relatively low transfer rate across the blood-brain barrier, wherein the improvement comprises cationizing said antibodies to provide cationized antibodies having an isoelectric point of between about 8.0 and 11.0, said cationized antibodies having increased rates of transfer across said blood-brain barrier.

7. A neuropharmaceutical composition according to claim 6 wherein said antibodies are monoclonal antibodies.

8. A neuropharmaceutical composition according to claim 7 wherein the isoelectric point of said cationized antibodies is between about 8.0 to 9.0.

9. A neuropharmaceutical composition according to claim 6 wherein said antibody is an antibody to an antigen selected from the group consisting of amyloid peptide of Alzheimer'"'"'s disease, human GFAP, human DR-antigen, or the human immunodeficiency virus (HIV).