Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Curedm Group Holdings, LLC

Victor M Garsky

Dong-Mei Feng

Allen I Oliff

Raymond E Jones

Deborah DeFeo-Jones

Stephen F Brady

Richard L Tolman

Samuel L Graham

S Jane deSolms

John Hannah

Jules A Shafer

Michael P Neeper

Yueming Li

James E Bruce

Lloyd H Waxman

Mohinder Sardana

Jenny M Wai

George P Vlasuk

Elizabeth Chen-Dodson

Xiaoting Tang

Robert B Stein

Roger M Freidinger

Gerald E Stokker

Robert P Gomez

Claresa S Levetan

Gene G Kinney

Paul M Keller

Edward M Scolnick

Catherine M Wiscount

John W Shiver

Joseph G Joyce

Loraine V Upham

Xiaoping Liang

Mark W Riemen

David C Heimbrook

Joseph M Pawluczyk

Elizabeth A Giuliani

Richard Colonno

Robert A Stein

Gene Kinney

Embodiments relate to proislet peptides, preferably HIP, that exhibit increased stability and efficacy, and methods of using the same to treating a pathology associated with impaired pancreatic function, including type 1 and type 2 diabetes and symptoms thereof.

Compositions and methods of using proislet peptides and analogs thereof

The invention provides compositions and methods for the treatment of diseases associated with amyloid deposits of A&#x3b2; in the brain of a patient, such as Alzheimer's disease. Such methods entail administering an immunogenic fragment of A&#x3b2;, lacking a T-cell epitope, capable of inducing a beneficial immune response in the form of antibodies to A&#x3b2;. In another aspect, the immunogenic fragment of A&#x3b2; is capable of elevating plasma A&#x3b2; levels. The immunogenic fragments comprise linear or multivalent peptides of A&#x3b2;. Pharmaceutical compositions comprise the immunogenic fragment chemically linked to a carrier molecule which may be administered with an adjuvant.

Peptide conjugate compositions and methods for the prevention and treatment of alzheimer's disease

The present invention provides synthetic &#x3b2;-secretase peptide substrates useful in various assays for measuring &#x3b2;-secretase activity. Antibodies that recognize the synthetic substrates and uses of the antibodies in various assays are disclosed. The herein disclosed peptide substrates are hydrolyzed at rates substantially faster than the attendant Swedish mutant APP from which the substrate sequences are derived.

Beta-secretase substrates and uses thereof

Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA), hydrophilic oligopeptide blocking groups and known cytotoxic agents are disclosed. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Conjugates useful in the treatment of prostate cancer

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

Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. The conjugates of the invention are characterized by attachment of the cleavable oligopeptide to the oxygen atom at the 4-position on a vinca drug that has be desacetylated. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Oligopeptides which comprise amino acid sequences that are recognized and proteolytically cleaved by free prostate specific antigen (PSA) are described. Also described are assays which comprise such oligopeptides useful for determining free PSA protease activity in vitro and in vivo. Therapeutic agents which comprise conjugates of such oligopeptides and known cytotoxic agents are also described.

Peptides

Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. The conjugates of the invention are characterized by a diamine linker between the oligopeptide and vinblastine. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Chemical conjugates which comprise oligopeptides, having amino acid sequences that are selectively proteolytically cleaved by free prostate specific antigen (PSA) and known cytotoxic agents are disclosed. Such conjugates are useful in the treatment of prostatic cancer and benign prostatic hypertrophy (BPH).

Assays which comprise oligopeptides and which are useful for determining free PSA protease activity in vitro and in vivo are described. Such oligopeptides comprise amino acid sequences that are recognized and proteolytically cleaved by free prostrate specific antigen (PSA). Also described are assays useful in identifying inhibitors of free PSA.

The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras farnesyl transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

Inhibitors of farnesyl-protein transferase

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Blue Bell, PA, United States of America

Victor M Garsky