California Biotechnology Inc.

Scios Nova, Inc.

Byk Gulden Lomberg Chemische Fabrik Gmbh

James W Schilling, Jr

Robert T White

Barbara Cordell

Bradley J Benson

Robert M Scarborough

Douglas I Buckley

Nobuhiko Katunuma

Phyllis A Ponte

Recombinant materials for the production of low molecular weight hydrophobic lung surfactant proteins are disclosed and claimed. The monomeric forms of the proteins from human and canine sources have apparent molecular weights of about 5 kd and form dimers under some conditions. The availability of these recombinant materials permits production of large amounts of these proteins through recombinant techniques and permits the use of these proteins in pharmaceutical compositions in the treatment of respiratory deficiency syndromes.

Recombinant alveolar surfactant protein

The complete coding sequences and amino acid sequences for both canine and human 32K alveolar surfactant proteins (ASP) are disclosed; clones encoding variants of the SP-18 and SP-5 forms of human protein are disclosed. Methods and vectors for obtaining these proteins in recombinant form are also described. An improved method for purification of the 32K protein takes advantage of its carbohydrate affinity. Pharmaceutical compositions in the treatment of respiratory deficiency syndrome use the 10K proteins with or without the 32K form. Synthetic peptides based on the human SP-5 protein are provided as well, which peptides show significant ASP activity.

Various specific human SP-18 and human SP-5 derived peptides have alveolar surfactant protein (ASP) activity. These peptides are prepared using synthetic methods or by recombinant techniques.

DNA encoding analogs of human alveolar surfactant protein SP-5

DNA sequences encoding .beta.-amyloid-related proteins associated with Alzheimer's disease are disclosed. Also provided herein is a DNA sequence encoding a novel protease inhibitor. These sequences are used in producing or constructing recombinant .beta.-amyloid core protein, .beta.-amyloid-related proteins and recombinant or synthetic immunogenic peptides. Antibodies generated against the recombinant proteins or immunogenic peptides derived therefrom can be used for cerebral fluid or serum protein diagnosis of Alzheimer's disease.

Recombinant Alzheimer's protease inhibitory amyloid protein and method

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.

Methods of treatment using Alzheimer's amyloid polypeptide derivatives

DNA encoding and expression systems for alveolar surfactant proteins

Various specific human SP-18 and human SP-5 derived peptides have alveolar surfactant protein (ASP) activity. These peptides are prepared using synthetic methods or by recombinant techniques. The peptides of the invention include surfactant proteins having serine replacements for the cysteines.

Alveolar surfactant proteins having cys to ser mutations

The complete coding sequences and amino acid sequences for both canine and human 32K alveolar surfactant proteins (ASP) are disclosed; clones for the 10K protein have also been obtained. Methods and vectors for obtaining these proteins in recombinant form are described. The availability of large amounts of these proteins through recombinant techniques permits the use of ASP in suitable pharmaceutical compositions in the treatment of respiratory deficiency syndromes.

Recombinant DNA sequence encoding Alveolar Surfactant Protein

Recombinant DNA sequence encoding alveolar surfactant protein

The complete coding sequences and amino acid sequences for both canine and human alveolar surfactant protein (ASP) are disclosed. Methods and vectors for obtaining these proteins in recombinant form are described. The availability of large amounts of these proteins through recombinant techniques permits the use of ASP in suitable pharmaceutical compositions in the treatment of respiratory deficiency syndromes.

Growing community of inventors

Palo Alto, CA, United States of America

James W Schilling, Jr