Emory University

Beth Israel Deaconess Medical Center, Inc.

University of Toronto

Massachusetts Institute of Technology

Georgia Tech Research Corporation

Baker Idi Heart and Diabetes Institute Holdings Limited

Elliot L Chaikof

Lijun Sun

Kacey Gribbin Marra

Axel Guenther

Richard D Cummings

Janine Orban

Hongbo Liu

Lian Leng

Venkata Krishnamurthy

John H Chon

June Feng

Carolyn A Haller

Stephanie Grainger

Mohammed Sardar

David Miranda Nieves

Shashi Malladi

Edward W Merrill

Karlheinz Peter

Richard M Cheng

Vincent Paul Conticello

Cynthia Rueyi Sung

Subramanian Baskaran

Zhifei Dai

Richard Yihsiu Cheng

Daniel Grande

Peter J Ludovice

Xue-Long Sun

Wookhyun Kim

Keith M Faucher

Xue Long Sun

Danijal Topcic

Wanxing Cui

Chrystelle S Cazalis

Venkata R Krishnamurthy

Richard Cheng

This disclosure relates to selectin inhibitors, compositions, and methods related thereto. In certain embodiments, the disclosure relates to glycopeptides that contain one or more modified amino acids conjugated to a saccharide or polysaccharide. In certain embodiments, the disclosure relates to uses of the glycopeptides as anti-inflammatory, antithrombotic, or anti-metastatic agents.

Selectin inhibitors, composition, and uses related thereto

Provided are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, tautomers, isotopically labeled derivatives, polymorphs, and prodrugs thereof, wherein X-X, R, R, R, n, and Ring A are as defined herein. The compounds may be aryl hydrocarbon receptor agonists or partial aryl hydrocarbon receptor agonists. Also provided are pharmaceutical compositions comprising a compound of Formula (I) and methods of using such compounds for treating diseases and conditions related to the activity of an aryl hydrocarbon receptor, such as, for example, inflammatory diseases, autoimmune diseases, metabolic disorders, and proliferative diseases.

Aryl hydrocarbon receptor modulators and uses thereof

Systems, devices and methods are provided for fabricating anisotropic polymer materials. According to various embodiments, a fluidic device is employed to distribute a polymer solution and a flow-confining solution in order to generate a layered flow, where the layered flow is formed such that a polymer liquid sheet is sheathed on opposing sides by flow-confining liquid sheets. The fluidic device includes first and second fluid conduits, where the first fluid conduit receives the layered flow. The second fluid conduit has a reduced height relative to the first fluid conduit, such that the layered flow is constricted as it flows through the second fluid conduit. The constriction formed by the second flow conduit causes hydrodynamic focusing, reducing the thickness of the polymer liquid sheet, and inducing molecular alignment and anisotropy within the polymer liquid sheet as it is hardened and as strain is applied during extrusion of the sheet.

Fluidic systems, devices and methods for inducing anisotropy in polymeric materials

Provided are compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, tautomers, isotopically labeled derivatives, polymorphs, and prodrugs thereof, wherein X-X, R, R, R, n, and Ring A are as defined herein. The compounds may be aryl hydrocarbon receptor agonists or partial aryl hydrocarbon receptor agonists. Also provided are pharmaceutical compositions comprising a compound of Formula (I) and methods of using such compounds for treating diseases and conditions related to the activity of an aryl hydrocarbon receptor, such as, for example, inflammatory diseases, autoimmune diseases, metabolic disorders, and proliferative diseases. 

This disclosure relates to selectin inhibitors, compositions, and methods related thereto. In certain embodiments, the disclosure relates to glycopeptides that contain one more modified amino acids conjugated to a saccharide or polysaccharide. In certain embodiments, the disclosure relates to uses of the glycopeptides as anti-inflammatory, anti-thrombotic, or anti-metastatic agents.

This disclosure relates to temperature sensitive conjugates, compositions, and uses related thereto. In certain embodiments, the disclosure relates to conjugate polymers comprising a) a temperature sensitive polymer and b) an antibody. Typically the antibody has an epitope to a platelet receptor. The antibody may be a single-chain antibody wherein the platelet receptor is GPIIb/IIIa, such as an anti-GPIIb/IIIa antibody. In certain embodiments, the antibody binds specifically to the activated conformation of GPIIb/IIIa, i.e., an activation-specific GPIIb/IIIa antibody.

Temperature sensitive conjugate compositions

In an embodiment, a number of synthetic protein triblock copolymers are provided comprising first and second end hydrophobic blocks separated by a central hydrophilic block. In particular, the synthetic proteins are elastin-mimetic proteins having improved mechanical characteristics and related methods of making the proteins with the capability of providing precise control over the mechanical properties. Provided are proteins used in a number of medical devices such as artificial blood vessels, shunts, stents or as embolic agents in situations where it is desired to stop or reduce blood flow or pressure in a localized region.

Modified protein polymers

The transmembrane human protein thrombomodulin (TM), as a critical regulator of the protein C pathway, represents the major anticoagulant mechanism that is operative in both normal and injured blood vessels under physiologic conditions in vivo. Compositions and methods are disclosed relating to thrombomodulin derivatives and conjugates, including methods for site-specific pegylation and compositions of a truncated thrombomodulin derivative.

Thrombomodulin derivatives and conjugates

The invention comprises anti-inflammatory conformal barriers with controllable permeability properties that can be applied to living cells prior to transplant, and methods for coating living cells with conformal barriers. The coatings comprise polymer layers deposited on a cell surface by layer-by-layer polymer assembly, wherein each layer contains a positive and a negative polymer pair. The barriers can be actively anti-inflammatory through incorporation of anticoagulant and/or anti-inflammatory agents into the barrier.

Method for coating living cells

A biocompatible biological component is provided comprising a membrane-mimetic surface film covering a substrate. Suitable substrates include hydrated substrates, e.g. hydrogels which may contain drugs for delivery to a patient through the membrane-mimetic film, or may be made up of cells, such as islet cells, for transplantation. The surface may present exposed bioactive molecules or moieties for binding to target molecules in vivo, for modulating host response when implanted into a patient (e.g. the surface may be antithrombogenic or antiinflammatory) and the surface may have pores of selected sizes to facilitate transport of substances therethrough. An optional hydrophilic cushion or spacer between the substrate and the membrane-mimetic surface allows transmembrane proteins to extend from the surface through the hydrophilic cushion, mimicking the structure of naturally-occurring cells. An alkylated layer directly beneath the membrane-mimetic surface facilates bonding of the surface to the remainder of the biological component. Alkyl chains may extend entirely through the hydrophilic cushion when present. To facilitate binding, the substrate may optionally be treated with a polyelectrolyte or alternating layers of oppositely-charged polyelectrolytes to facilitate charged binding of the membrane-mimetic film or alkylated layer beneath the membrane-mimetic film to the substrate. The membrane-mimetic film is preferably made by in situ polymerization of phospholipid vesicles.

Biological component comprising artificial membrane

A glycopolymer composition is provided comprising glycopolymer molecules having a polymer backbone; a first pendent unit comprising a linking group connected to said polymer backbone and a saccharide moiety connected to said linking group, optionally a second pendent unit; a phenyl ring at a first end of the polymer backbone; and a cyanoxyl group at the second end of the polymer backbone, useful as intermediates for making bioactive glycopolymers which bind to bioactive molecules, viruses, cells and substrates for protein separation, cell culture, ad drug delivery systems, as well as in targeting for treatment of wound healing and other pathological conditions.

Glycopolymers and free radical polymerization methods

The present Specification describes materials and methods which provide for improved performance of medical prostheses, including vascular graft material, artificial heart valves, and other implanted materials. The materials comprising bound thrombomodulin or a functionally equivalent derivative protein, provide for fewer undesirable side effects including inflammation, thromboses and neointimal hyperplasia.

Antithrombogenic membrane mimetic compositions and methods

A modular cytomimetic biocompatible biomaterial, comprising a phospholipid or phospholipid derivative comprising various functional groups (e.g., lipid, peptide, sugar) having specific chemical properties which can function as a modular surface design unit to be incorporated or appended to a desired substrate (e.g., a polymer or a metal) on which it is then polymerized in situ, thereby contributing new or specified biochemical characteristics to the polymerized and stabilized biomaterial.

Modular cytomimetic biomaterials, transport studies, preparation and utilization thereof

The present invention provides a biocompatible material, comprising a phospholipid or phospholipid derivative comprising various functional groups having specific chemical properties, which can function as a modular surface design unit to be incorporated or appended to a desired substrate on which it is then polymerized, thereby contributing new or specified biochemical characteristics to the polymerized and stabilized biomaterial.

Growing community of inventors

Atlanta, GA, United States of America

Elliot L Chaikof