Methods of treatment using Alzheimer's amyloid polypeptide derivatives

• US 5,187,153 A
• Filed: 03/29/1990
• Issued: 02/16/1993
• Est. Priority Date: 11/17/1986
• Status: Expired due to Term

• Current Assignee: Scios, Inc. (Johnson & Johnson)
• Original Assignee: Scios, Inc. (Johnson & Johnson)
• Inventors: Schilling, James W., Cordell, Barbara, Katunuma, Nobuhiko
• Primary Examiner(s): Draper, Garnette D.
• Assistant Examiner(s): Ossanna, Nina
• Application Number:
  US07/502,273
• Time in Patent Office: 1,055 Days
• Field of Search: 514/12, 530/324, 435/69.7, 900/250
• US Class Current: 514/20.4
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• 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: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 14/8114 Kunitz type inhibitors
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/38 against protease inhibitors of peptide structure
• CPC Class Codes: C12N 15/71 Expression systems using regulatory sequences derived from the trp-operon
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Pharmaceutical compositions containing a 57 amino acid protease inhibitor and uses for those compositions are taught. The protease inhibitor is referred to as A4i which is associated with Alzheimer'"'"'s disease. In addition to the A4i protease, other analogs are taught as are pharmaceutical compositions containing such analogs and their uses in treating a variety of abnormalities associated with Kunitz-type basic protease inhibitors. For example, it has been found that pharmaceutical compositions containing A4i protease and analogs thereof inhibit plasmin and tryptase, and also inhibit pancreatic trypsin, alpha-chymotrypsin, tissue kallikrein and serum kallikrein. In that certain diseases are associated with a general release of proteases such as trypsin, chymotrypsin and elastase into the circulatory system pharmaceutical compositions containing A4i and analogs thereof can be used in the management of such diseases.

Claims

1. A method of treating an individual having excessive activity of serine proteases, comprising:

administering to the individual in need thereof a pharmaceutically effective amount of the composition, comprising;

a pharmaceutically acceptable carrier; and

a protein analog wherein the amino acid corresponding to arginine at position 13 in the sequence ##STR9## is substituted with a neutral hydrophobic amino acid.

2. The method as claimed in claim 1, wherein the serine protease inhibited by the protein analog is elastase and the neutral hydrophobic amino acids is valine.

3. The method as claimed in claim 1, wherein the excessive activity of serine proteases is associated with emphysema.