Kosan Biosciences Incorporated

Prolynx LLC

University of California

Chiron Corporation

Other

Bristol-myers Squibb Compnay

Daniel V Santi

Gary W Ashley

Chaitan Khosla

William J Rutter

Daniel T Chu

Brian R Hearn

Christopher Reeves

Jeffrey C Henise

David C Myles

Zong-Qiang Tian

Kai Wu

Michael A Siani

Philip J Barr

Robert G McDaniel

Ronald N Zuckermann

Christopher Carreras

Yaoquan Liu

Rainer Ziermann

Reyna J Simon

James T Kealey

Paul A Bartlett

Verena D Heubner

Linda C Dayem

Steven D Dong

Andreas W Schirmer

Maria Fardis

Mark A Burlingame

Zhan Wang

Eric L Schneider

Shaun Fontaine

C Richard Hutchinson

Robert Johnson

Yi-Qing Zhou

Li Feng

Qun Xue

Brian Walter Metcalf

Zhihao Hu

Hong Fu

Li Tang

Ralph C Reid

Verena D Huebner

Yue Chen

Simon James Shaw

Kurt Frederick Sundermann

Jeffrey C Edman

Eduardo J Rodriguez

Ursula Edman

Larry Peck

Provided herein are releasable conjugates of inhibitors of DNA damage response suitable for use as therapeutic agents in the treatment of disease.

Conjugated inhibitors of DNA damage response

Conjugates of topoisomerase I inhibitors linked to a macromolecule through a linkage that undergo beta elimination in situ in combination with one or more of an assessed defect in DNA damage response (DDR) in a subject bearing cancer, a cell cycle checkpoint inhibitor and/or a DDR inhibitor provides improved outcomes for cancer-bearing subjects.

Synergistic cancer treatment

Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals.

Hydrogels with biodegradable crosslinking

Conjugates of carriers and hydrogels for controlling the biological half-life of somatostatin and its analogs are disclosed.

Conjugates of somatostatin analogues

Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals. This invention provides hydrogels that degrade to smaller, soluble components in a non-enzymatic process upon exposure to physiological conditions and to methods to prepare them. The hydrogels are prepared from crosslinking agents that undergo elimination reactions under physiological conditions, thus cleaving the crosslinking agent from the backbone of the hydrogel. The invention also relates to the crosslinking agents themselves and intermediates in forming the hydro gels of the invention. The biodegradable hydro gels prepared according to the methods of the invention may be of use in diverse fields, including biomedical engineering, absorbent materials, and as carriers for drug delivery.

The present invention provides methods and compositions that permit controlled and prolonged drug release in vivo. The compounds are either prodrugs with tunable rates of release, or conjugates of the drug with macromolecules which exhibit tunable controlled rates of release.

Prodrugs and drug-macromolecule conjugates having controlled drug release rates

The invention relates to solid supports useful in medical applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the solid support through a linkage that releases the drug or a prodrug through controlled beta elimination.

Controlled release from solid supports

The invention relates to conjugates of macromolecular carriers and drugs comprising linkers that release the drug or a prodrug through rate-controlled beta-elimination, and methods of making and using the conjugates.

Controlled release from macromolecular conjugates

The invention relates to compositions that comprise dendrimers useful in medical and veterinary applications that provide controlled release of drugs, such as peptides, nucleic acids and small molecules. The drugs are covalently coupled to the dendrimer through a linkage that releases the drug or a prodrug through controlled beta elimination.

Controlled drug release from dendrimers

Esters of compounds in the leptomycin family, having a structure according to formula I where R, R, R, R, R, and Rare as defined herein, exhibit anti-tumor properties.

Esters of compounds in the leptomycin family

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San Francisco, CA, United States of America

Daniel V Santi