Dennis E Discher, 60205 Saint Marks Sq, Philadelphia, PA 19104

7217427, May 15, 2007

Jul 1, 2004

10/882816

Dennis E. Discher - Philadelphia PA, US
Bohdana M. Discher - Philadelphia PA, US
James C-M Lee - Columbia MO, US
Daniel A. Hammer - Villanova PA, US
Frank Bates - Minneapolis MN, US

The Trustees of the University of Pennsylvania - Philadelphia PA
Regents of the University of Minnesota - Minneapolis MN

A61K 9/127

424450, 424 121, 424 9321, 424 951, 424417, 424489, 424502, 4284022, 264 41, 264 43

The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a “polymersome. ” The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.

7867512, Jan 11, 2011

Feb 20, 2007

11/708932

Dennis E. Discher - Philadelphia PA, US
Bohdana M. Discher - Philadelphia PA, US
James C-M Lee - Columbia MO, US
Daniel A. Hammer - Villanova PA, US
Frank Bates - Minneapolis MN, US

The Trustees of the University of Pennsylvania - Philadelphia PA
Regents of the University of Minnesota - Minneapolis MN

A61K 9/127

424450

The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a “polymersome. ” The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.

2005000, Jan 6, 2005

Mar 29, 2004

10/812292

Dennis Discher - Philadelphia PA, US
Fariyal Ahmed - Philadelphia PA, US

A61K009/127
B01J013/02
B01J013/04

424490000, 264004100

The present invention provides methods for preparing stable, purely synthetic, self-assembling, controlled release, polyethylene oxide (PEO)-based polymersome vesicles, and the resulting PEO-based polymersomes capable of such controlled release, and methods of use therefor for the controlled transport and delivery of encapsulatable active agents contained therein. Further provided are methods for controlling destabilization of the vesicle membrane and the resulting hydrolysis-triggered, controlled release of active agent(s) encapsulated in the vesicle by controlling the blend ratio (mol %) of hydrolysable PEO-block copolymer of the hydrophilic component(s) and of the more hydrophobic PEO-block copolymer component(s) to produce amphiphilic high molecular weight PEO-based polymersomes, wherein the PEO volume fraction (f) and chain chemistry control encapsulant release kinetics from the copolymer vesicles and the polymersome carrier membrane destabilization.

2005018, Aug 18, 2005

Aug 6, 2004

10/913660

Dennis Discher - Philadelphia PA, US
Paul Dalhaimer - Sheboygan WI, US

A61K048/00
A61K049/00
A61K009/127

424009520, 424450000, 514044000, 514002000

Provided are worm-like micelles, capable of encapsulating at least one encapsulant, wherein each worm-like micelle comprises one or more wholly synthetic, polymeric, super-amphiphilic molecules that self assemble in aqueous solution, without organic solvent or post assembly polymerization; and wherein at least one of said super-amphiphilic molecules is a hydrophilic block copolymer, the weight fraction (w) of which, relative to total copolymer molecular weight, directs assembly of the amphiphilic molecules into the worm-like micelle of up to one or more microns in length, and determines its stability, flexibility and convective responsiveness. Also provide are methods of preparing and methods of using the worm-like micelles, particularly when loaded with one or more encapsulants. The loaded worm-like micelles of the present invention are particularly suited for the stable and controlled transport, delivery and storage of materials, either in vivo or in vitro.

2006016, Jul 27, 2006

Dec 28, 2005

11/320198

Dennis Discher - Philadelphia PA, US
Yan Geng - Langhorne PA, US

A61K 38/17
A61K 48/00
A61K 9/50
A61K 33/00
A61K 31/56
A61K 9/16

424490000, 424600000, 514002000, 514044000, 514169000

Provided is a method of controlling the release of at least one encapsulated active agent from a worm-like micelle, wherein each worm-like micelle comprises one or more amphiphilic block copolymers that self assemble in aqueous solution, without organic solvent or post assembly polymerization; wherein at least one of said amphiphilic molecules is a hydrophilic block copolymer and at least one of said amphiphilic molecules is a hydrophobic block copolymer which is hydrolyticaly unstable in the pH range of about 5 to about 7. The loaded worm-like micelles of the present invention are particularly suited for the stable and controlled transport, delivery and storage of materials, either in vivo or in vitro.

2007019, Aug 16, 2007

Feb 10, 2006

11/351420

Adam Engler - Philadelphia PA, US
H. Sweeney - Philadelphia PA, US
Dennis Discher - Philadelphia PA, US

C12N 5/02
C12N 5/00

435325000

Provided are methods for the selection and regulation of the mechanical properties of substrates or tissue microenvironments as a technique to regulate in vitro differentiation, cell shape and/or lineage commitment of anchorage-dependent cells, such as mesenchymal stem cells into, e.g., neurogenic-, myogenic-, and osteogenic-type cells. Substrate mechanical properties include elasticity, tension, adhesion, and myosin-based contractile mechanisms. Inhibitors can be introduced to further regulate differentiation.

2008018, Jul 31, 2008

Nov 14, 2007

11/985311

Dennis E. Discher - Philadelphia PA, US
Fariyal Ahmed - Boston MA, US

A61K 9/127
A61K 47/30
A61P 35/00
A61K 31/337
A61K 31/704

424450, 5147723, 514449, 514 34

Provided are methods for preparing and delivering stable, purely synthetic, self-assembling, controlled release, polyethylene oxide (PEO)-based polymersome vesicles, and the resulting PEO-based polymersomes capable of such controlled release, and methods of use therefor for the controlled transport and delivery of encapsulatable, cytotoxic, anticancer active agents contained therein. Further provided are methods for controlling destabilization of the vesicle membrane and the resulting hydrolysis-triggered, controlled release of active agent(s) encapsulated in the vesicle by controlling the blend ratio (mol %) of hydrolysable PEO-block copolymer of the hydrophilic component(s) and of the more hydrophobic PEO-block copolymer component(s) to produce amphiphilic high molecular weight PEO-based polymersomes, wherein the PEO volume fraction (f) and chain chemistry control encapsulant release kinetics from the copolymer vesicles and the polymersome carrier membrane destabilization.

2009022, Sep 3, 2009

Dec 15, 2006

12/086680

Shuhui Qin - Barlett IL, US
Shu Yang - Blue Bell PA, US
Dennis Discher - Philadelphia PA, US
Yan Geng - Langhorne PA, US

A61K 9/14

424501

Provided are thermo-responsive polymersomes, which display cold-controlled encapsulation near the physiological temperatures, and have a PDI less than 1.2. Morphology of the thermo-responsive polymersomes is a function of the weight fraction of the hydrophilic block in the block copolymer and the number average molecular weight (M) of the block copolymer. When the lower critical solution temperature (LCST) is at, or slightly above physiological temperature, the thermo-responsive block displays hydrophobic properties, such that the block copolymer self-assembles in aqueous solution to form a polymersome with the thermo-responsive block occupying the core of the polymersome and the hydrophilic block occupying the corona of the polymersome. Below the LCST, the thermo-responsive block displays hydrophilic properties, such that the polymersome dissociates, providing fast release of an active agent encapsulated therein.