University of Illinois

Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Dow Global Technolgoies LLC

California Institute of Technology

Cerulean Pharma Inc.

Insert Therapeutics, Inc.

Jianjun Cheng

Hanze Ying

Robert Samuel Langer

John A Rogers

Mark E Davis

Yanfeng Zhang

Omid C Farokhzad

Stephen E Zale

Benjamin A Teply

SukWon Hwang

Rong Tong

Hua Lu

Menghua Xiong

Seung-Kyun Kang

Stephen W King

Alan P Kozikowski

Xue Chen

Jin S Yu

Kay T Khin

Hector Gonzalez

Robert S Langer, Jr

Li Tang

Nathalie C Bellocq

Suzie Hwang Pun

Robert S Langer

Kaimin Cai

Ziyuan Song

Sangyong Jon

Omid C Farokhazd

Hua Wang

Yan Bao

Yin Lichen

Lin-Feng Chen

Nathan Gabrielson

Lichen Yin

Benjamin A Tepley

Steve King

This disclosure relates generally to bleach activator compositions. This disclosure relates more particularly to tetraacetyldiamine and/or triacetyldiamine derivatives and compositions thereof and to their use as bleach activators, and methods for using them as detergents or biocides.

Tetraacetyldiamine and triacetyldiamine derivatives useful as bleach activators

Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl-drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity. Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds.

Trigger-activatable sugar conjugates for cancer-selective labeling and targeting

The disclosure provides a class of pH-sensitive, helix/random conformation switchable antimicrobial polypeptide (HRS-AMP) compositions as a single agent to selectively kill bacteria (e.g.,) under acidic condition in the stomach with diminished bacterial resistance compared to currently used antibiotics. Methods of treating bacterial infections in the stomach are also provided.

Conformation switchable antimicrobial peptides and methods of using the same

The invention provides antimicrobial polypeptides (AMPs) with high radial amphiphilicity. Unlike typical AMPs characterized by facial amphiphilicity or biomimetic antimicrobial polymers with randomly distributed charged and hydrophobic groups, these new AMPs are homo-polypeptides with radially amphiphilic structure. They adopt a stable &#x3b1;-helical conformation with a hydrophobic helical core and a charged exterior shell, formed by flexible hydrophobic side chains with terminal charge group. The radially amphiphilic polypeptides offer several advantages over conventional AMPs with regard to stability against protease and simplicity of design. They also exhibit high antibacterial activity against both Gram-negative and Gram-positive bacteria and low hemolytic activity. The AMPs thus provide a general platform for treating drug-resistant bacterial infections.

Antimicrobial alpha-helical cationic polypeptides

Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl-drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity. Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds of the invention.

Trigger-activatable metabolic sugar precursors for cancer-selective labeling and targeting

The present invention relates to polymers having dynamic urea bonds and more specifically to polymers having hindered urea bonds (HUBs) with fast hydrolytic kinetics. These urea bonds are aryl-substituted, i.e. aromatic-substituted hindered urea bonds, that demonstrate pH independent hydrolytic kinetics, such that they consistently and rapidly hydrolyze in water from pH 2 to 11. The urea bond dissociation for these materials is generally such that k&#x3e;h, which is two orders of magnitudes faster than for aliphatic hindered ureas. The present invention also relates to hydrolytically reversible or degradable linear, branched or network polymers incorporating these HUBs and to precursors for incorporation of these HUBs into these polymers. The technology can be applied to and integrated into a variety of polymers, such as polyureas, polyurethanes, polyesters, polyamides, polycarbonates, polyamines, and polysaccharides to make linear, branched, and cross-linked polymers. Polymers incorporating these HUBs can be used in a wide variety of applications including for example, environmentally compatible packaging materials and biomedical applications, such as drug delivery systems and tissue engineering. In other embodiments, the HUBs can be used in self-healing polymers.

Dynamic urea bonds with fast hydrolytic kinetics for polymers

The present invention relates to a one-component processing method and system for preparing polyurea materials. This method and system involves a polymerization process using cyclic oligomeric polyurea precursors. These cyclic oligomeric precursors have dynamic urea bonds such as hindered urea bonds (HUBs). These cyclic oligomeric precursors exhibit dynamic properties to reversibly dissociateyielding isocyanate and amine components which polymerize to yield the polyureas, such as linear, branched or cross-linked polyureas. This method and system has advantages over conventional methods that utilize two-component systems. Such two-component systems require the segregation of the isocyanate and amine components to prevent premature or too rapid polymerization. The resulting polyureas are useful for a variety of applications including coatings.

Cyclic dynamic polyureas for polymeric urea processing

Disclosed are 2-phenyl-cyclopropylmethanamines which are selective 5-HT(2C) receptor agonists and are used in the treatments of diseases and conditions wherein modulation of 5-HT(2C) receptors provides a benefit, such as obesity and psychiatric disorders.

Cyclopropylmethanamines as selective 5-HT(2C) receptor agonists

The invention provides transient devices, including active and passive devices that physically, chemically and/or electrically transform upon application of at least one internal and/or external stimulus. Incorporation of degradable device components, degradable substrates and/or degradable encapsulating materials each having a programmable, controllable and/or selectable degradation rate provides a means of transforming the device. In some embodiments, for example, transient devices of the invention combine degradable high performance single crystalline inorganic materials with selectively removable substrates and/or encapsulants.

Transient electronic devices comprising inorganic or hybrid inorganic and organic substrates and encapsulates

The invention provides polymers comprising Formula I: wherein monomer is a repeating unit comprising 2, 3, 4, 5, 6 or 7 carbon atoms and the monomers are linked together through amide or ester bonds; n is about 6 to about 1000; and Linker is an optionally substituted carbon chain that is optionally interrupted by moieties such as oxygen, nitrogen, sulfur, phosphorus, or silicon. Charge is a moiety having a positive or negative charge on a heteroatom, such as nitrogen, oxygen, phosphorus, or sulfur; where the Linker separates the monomer and the Charge by at least six linear atoms. The invention also provides methods of preparing the polymers and the copolymers and methods of using the polymers and copolymers, for example, as drug delivery systems, as membrane penetrating peptides, and as therapeutic agents.

Stable helical ionic polypeptides

The disclosure provides reversible polymers from polyurea by modifying the nitrogen atom with hindered substituents. The reversibility of hindered urea bond (HUB) can be controlled by changing the bulkiness of the substituents, and N-tert-butyl-N-ethylurea (TBEU), with its high binding constant and short lifetime, is applicable in the design of reversible polymer and self-healing materials at mild temperatures without external stimuli. HUB can be used in the design of smart materials with its adjustable reversibility, facile synthesis, and compatibility with many other polymer structures.

Dynamic urea bonds for reversible and self-healing polymers

Methods for efficient preparation of drug-polymer (or oligomer) conjugates useful in the preparation of particles, including microparticles and nanoparticles, for delivery of the drug in vivo for therapeutic applications are provided. The invention also provides nanoparticles prepared by nanoprecipitation using drug-polymer/oligomer conjugates of the invention. The drug conjugates are formed during polymerization of the polymer or oligomer in which the drug is employed as an initiator of the polymerization of the monomers which form the polymer and/or oligomer. More specifically, the drug conjugates are formed by ring-opening polymerization of cyclic monomers in the presence of an appropriate ring-opening polymerization catalyst and the initiator (the drug). The method is particularly useful for formation of polymer/oligomer conjugates with drugs and other chemical species containing one or more hydroxyl groups or thiol groups.

Particulate drug delivery methods

The invention provides multifunctional supramolecular self-assembled nanoparticles (SSNPs) comprising a set of rationally designed components that collectively facilitate efficient intestinal absorption of siRNA. The nanoparticles can induce potent TNF-&#x3b1; silencing in macrophages. Single gavage of SSNPs in mice depleted systemic TNF-&#x3b1; production at an siRNA dose as low as 50 &#x3bc;g/kg, and protected the mice from lipopolysaccharide-induced hepatic injury.

Nanoparticle mediated delivery of siRNA

Disclosed are polymers containing a backbone comprising alternating N-protected hydroxymethylaniline units ('spacer') and linker units.

Trigger-responsive chain-shattering polymers

The invention provides a composition comprising two or more of a) genetic material; b) a condensing agent; c) a membrane destabilizing agent; d) a targeting/stabilizing agent, and optionally e) an ionic cross-linking agent. The components of the composition can self-assemble to form particles via electrostatic and/or lipophilic interactions. Methods of making and using the composition are also provided. The compositions can be used, for example, to transfer genetic material to cells in vitro or in vivo.

Growing community of inventors

Champaign, IL, United States of America

Jianjun Cheng