Method of using cell surface receptor targeted molecules for the treatment of viral diseases

• US 6,074,636 A
• Filed: 06/05/1995
• Issued: 06/13/2000
• Est. Priority Date: 03/07/1991
• Status: Expired due to Term

• Current Assignee: Eisai Incorporated (Eisai Medical Research Incorporated)
• Original Assignee: Seragen, Inc. (Ligand Pharmaceuticals, Inc.)
• Inventors: Nichols, Jean C.
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US08/465,541
• Time in Patent Office: 1,835 Days
• Field of Search: 424/85.1, 424/85.2, 424/143.1, 424/144.1, 514/2, 514/8, 514/12, 514/885, 514/21
• US Class Current: 424/85.2
• 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 47/642 the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07K 14/34 from Corynebacterium (G)
• CPC Class Codes: C07K 14/5406 IL-4
• CPC Class Codes: C07K 14/5412 IL-6
• CPC Class Codes: C07K 14/55 IL-2
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/55 containing a fusion with a toxin, e.g. diphteria toxin
• CPC Class Codes: C07K 2319/75 containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Abstract

The invention features a method for treating a patient infected with a virus. The method includes administering to the patient a molecule which is capable of specifically binding to a proteinaceous cell receptor expressed on a cell of the patient which cell contributes to the disease state of the patient, the molecule being capable of decreasing the viability of the cell.

Claims

1. A method for inhibiting virus replication in a patient, said virus causing a disease state in said patient without transforming cells of said patient infected by said virus, said method comprising administering to said patient a hybrid molecule which specifically binds targets cells bearing a high affinity, interleukin-2 receptor induced by infection by said virus, said hybrid molecule comprising a first and a second portion, said first portion comprising a molecule that kills or interferes with proliferation of said cells bearing high affinity interleukin-2 receptor and said second portion comprising a molecule that specifically binds to the high affinity interleukin-2 receptor.

2. The method of claim 1 wherein said virus is human immunodeficiency virus.

3. The method of claim 1 wherein said virus is EBV.

4. The method of claim 1 wherein said interleukin-2 receptor is the high affinity interleukin-2 receptor.

5. The method of claim 1 wherein said molecule kills cells bearing said interleukin-2 receptor.

6. The method of claim 1 wherein said second portion comprises all or a binding portion of an antibody specific for said interleukin-2 receptor.

7. The method of claim 1 wherein said second portion comprises all or an interleukin-2 receptor binding portion of interleukin-2.

8. The method of claim 1 wherein said first portion comprises a cytotoxin.

9. The method of claim 8 wherein said cytotoxin is a fragment of a peptide toxin which is enzymatically active but which does not possess generalized eukaryotic receptor binding activity.

10. The method of claim 9 wherein said fragment of a peptide toxin comprises fragment A of diphtheria toxin and enough of fragment B of diphtheria toxin to form a pore in a cell membrane.

11. The method of claim 10 wherein said molecule is DAB₄₈₆ IL-2.

12. The method of claim 10 wherein said molecule is DAB₃₈₉ IL-2.

13. The method of claim 10 wherein said molecule is DAB₄₈₆ IL-4.

14. The method of claim 10 wherein said molecule is DAB₄₈₆ IL-6.

15. The method of claim 1 wherein said molecule comprises all or a binding portion of an antibody specific for said interleukin-2 receptor.

16. The method of claim 15 wherein said antibody is a complement activating antibody.

17. A method for inhibiting HIV replication in a patient, comprising administering to said patient a hybrid molecule which specifically targets cells bearing an interleukin-4 receptor induced by infection by HIV, said hybrid molecule comprising a first and a second portion, said first portion comprising a molecule that kills or interferes with proliferation of said cells bearing an interleukin-4 receptor and said second portion comprising a molecule that specifically binds to the interleukin-4 receptor.

18. The method of claim 17 wherein said molecule is DAB₃₈₉ IL-4.

19. A method for inhibiting HIV replication in a patient, comprising administering to said patient a hybrid molecule which specifically targets cells bearing an interleukin-6 receptor induced by infection by HIV, said hybrid molecule comprising a first and a second portion, said first portion comprising a molecule that kills or interferes with proliferation of said cells bearing an interleukin-6 receptor and said second portion comprising a molecule that specifically binds to the interleukin-6 receptor.

20. The method of claim 19 wherein said molecule is DAB₃₈₉ IL-6.