Scios Nova, Inc.

California Biotechnology Inc.

The University of North Carolina at Chapel Hill

Macronex, Inc.

Byk Gulden Lomberg Chemische Fabrik Gmbh

Other

Bradley J Benson

James W Schilling, Jr

Robert T White

Douglas I Buckley

Barbara Cordell

Robert M Scarborough

Susan L Morris-Natschke

Khalid S Ishaq

David D Lesikar

Jose-Luis Diaz

Ronald J Uhing

George J Cianciolo

Xiannong Chen

Henry Wong

Kate B Silverness

Asha Naidu

Michael C Venuti

Steven Shak

John T Stults

Kathleen A Shiffer

Cynthia P Quan

John H Frenz

JoRae Wright

Stable lung surfactant compositions are provided, as well as methods for their preparation, modification, formulation, assay, and therapeutic use.

Surfactant compositions and methods

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

Novel hydroxyalkylammonium-pyrimidine of the formula ##STR1## and nucleoside derivatives have been found to be useful as inhibitors of inflammatory cytokines. They can be used, inter alia, in the therapy of septic shock, cachexia, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and AIDS. The compounds are typically prepared by reaction of an iodo substituted nucleoside with the appropriately substituted hydroxyalkylamine.

Hydroxyalkylammonium-pyrimidines and nucleoside derivatives, useful as

Novel N-substituted-(dihydroxyboryl)alkyl purine, indole and pyrimidine derivatives have been found to be useful as inhibitors of inflammatory cytokines. They can be used, inter alia, in the therapy of septic shock, cachexia, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and AIDS. The compounds are typically prepared by reaction of an bromoalkyl boronic acid with the purine, indole or pyrimidine base.

N-substituted-(Dihydroxyboryl)alkyl purine, indole and pyrimidine

Hydroxyalkylammonium-pyrimidines or purines and nucleoside derivatives,

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.

Methods are provided for the isolation and purification of recombinant lung surfactant protein. The methods involve a multistep procedure including extraction with a C.sub.1 -C.sub.4 aliphatic alcohol and chromatographic purification steps which employ a C.sub.1 -C.sub.4 aliphatic alcohol as eluant. Purified proteins obtained using the disclosed isolation and purification steps are provided as well.

Isolation and purification of lung surfactant protein

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 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

Pulmonary administration of a pharmaceutically active substance useful for local or systemic action which comprises, liposomes containing an effective amount of a pharmaceutically active substance, and an amount of alveolar surfactant protein effective to enhance transport of the liposomes across a pulmonary surface.

Pulmonary administration of pharmaceutically active substances

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

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San Francisco, CA, United States of America

Bradley J Benson