Merck + Co., Inc.

Edward M Scolnick

William F Hoffman

Robert L Smith

Arnold J Repta

Alfred W Alberts

William J McAleer

Victor M Garsky

Allen I Oliff

Ronald W Ellis

Gregory D Berger

Robert S Lowe

Raymond E Jones

Elliott D Kieff

Deborah DeFeo-Jones

E Dale Lehman

Albert J Robichaud

Robert W Marquis, Jr

Joanne E Tomassini

D Eugene Wampler

Joseph V Hughes

Ted F Schaefer

Robert A Zivin

Arthur Friedman

Novel pharmaceutical compositions useful for the treatment of benign prostatic hyperplasia which comprises novel oligopeptides, which are selectively cleaved by enzymatically active PSA, in conjugation with a cytotoxic agent are described. Methods of treating benign prostate hypertrophy are also disclosed.

Conjugates useful in the treatment of benign prostatic hyperplasia

The invention encompasses a method of inhibiting bone resorption in patients in need of such inhibition to a degree sufficient to halt or retard loss of bone mass, reduce fractures, improve bone repair and prevent or treat osteoporosis comprising: the administration of a non-toxic therapeutically effective amount of a selective cyclooxygenase-2 inhibitor such as the compounds of formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for the purposes described above.

Method of preventing bone loss

The instant invention is directed to a method for enhancing the lowering of plasma cholesterol level in a subject in need thereof which comprises the time-controlled administration of a nontoxic therapeutically effective amount of an HMG-CoA reductase inhibitor to said subject which surprisingly affords an equivalent or improved reduction of plasma cholesterol levels while significantly reducing the amount of HMG-CoA reductase inhibitor circulating in the bloodstream of the subject as compared to the same parameters when the oral administration of a conventional rapid release dosage form is utilized.

Method for enhancing the lowering of plasma-cholesterol levels

A vaccine strain of varicella-zoster virus (VZV), tested in clinical trials, is capable of preventing chickenpox in children. This virus has been modified by the introduction into its genome of heterologous DNA which encodes an immunogenic polypeptide of another human pathogen. This heterologous polypeptide is expressed in cells infected by the recombinant virus. Such recombinant VZV is useful as a vaccine for chickenpox as well as for heterologous pathogens.

Varicella-zoster virus as a live recombinant vaccine

Disclosed herein are compounds of structural formula (I) ##STR1## which are useful as cholesterol lowering agents. These compounds are also useful as inhibitors of squalene synthase, inhibitors of fungal growth, inhibitors of farnesyl-protein transferase and farnesylation of the oncogene protein Ras. These compounds are also useful in the treatment of cancer.

Cholesterol lowering compounds

Method for enhancing the lowering of plasma cholesterol levels

A DNA fragment encoding at least part of the ANF protein has been molecularly cloned and its nucleotide sequence partially determined. The composition and sequence of a peptide containing 116 amino acids within the ANF gene have been determined. Biologically active subunit peptides have been identified.

Cardiac atrial peptides

Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors which are useful as antihypercholesterolemic agents and are represented by the following general structural formulae (I) or (II): ##STR1## wherein: n is 1 to 5;

HMG-CoA reductase inhibitors

The surface antigen protein of human Hepatitis B virus is synthesized in Saccharomyces cerevisiae as a 23,000-26,000 dalton polypeptide, essentially free of intermolecular disulfide bonds. This antigen is a poor immunogen in animals and man. No prior precedent or method exists for efficiently converting the non-disulfide bonded antigen to a fully intermolecular disulfide bonded particle. We describe the first example of such a conversion in vitro and show that the act of this conversion enhances the immunogenicity of the antigen about 10-fold. The in vitro conversion makes practical the production of hepatitis B surface antigen from microorganisms using recombinant DNA methods.

Immunogenic HbsAg derived from transformed yeast

Novel HMG-CoA reductase inhibitors

A surface structural protein of Hepatitis A Virus (HAV) has been isolated and characterized from virus grown in tissue culture. This 33,000 dalton viral protein (VP-1) reacts with immune HAV sera and monoclonal antibodies that neutralize HAV infectivity. The VP-1 is usable for the preparation of a polypeptide subunit vaccine for HAV. Hybridoma cells were made which produced monoclonal antibodies to HAV or VP-1. These monoclonal antibodies were found to neutralize the infectivity of HAV and to compete with polyclonal antibody derived from human HAV immune sera. The monoclonal antibodies are useful for the neutralization of infectious HAV, the detection of antibodies to neutralizing sites on HAV, and the diagnoses of HAV disease in humans and other susceptible hosts.

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Wynnewood, PA, United States of America

Edward M Scolnick