Vivorx, Inc.

Clover Consolidated, Ltd.

Roswitha E Heintz

Patrick Soon-Shiong

Neil P Desai

Paul A Sandford

Gudmund Skjak-Braek

Francesco Curcio

Andrew Sojomihardjo S

Nilesh Ron

In accordance with the invention, there are provided methods, capsules, and delivery systems useful in preparing biological containment systems with properties (e.g., mechanical strength, capsule permeability and porosity, desired controlled release rates of the biologic or components secreted by the biologic, and immunoreactivity) that can be varied to adapt to a broader range of physiological conditions than known biological containment systems. There are also provided methods of making capsules containing cell aggregates therein, as well as the capsules formed thereby, which are useful as a quantitatively plentiful and low cost alternative to usage of freshly harvested cell aggregates (e.g., islets from pancreas), since the latter are usually available only in limited numbers.

Cytoprotective biocompatible containment systems for biologically active materials and methods of making same

The present invention is directed to a method of treating a patient with diabetes by implanting an improved macrocapsule containing living islet cells in the patient. The improved macrocapsules encapsulate microcapsules containing islet cells, to make the system more biocompatible by decreasing the surface area and surface roughness of microencapsulated biological materials; increasing stability of microencapsulated islet cells; enhancing cytoprotectivity by increasing diffusion distance of encapsulated islet cells from cytotoxins secreted in vivo; providing retrievability of microencapsulated material; and providing a system of sustained release of the cellular products.

Method of treating patients with diabetes

In accordance with the present invention, there are provided methods to render cells non-adhesive and/or non-immunogenic with respect to macromolecules typically encountered in culture media or in physiological media.

Graft copolymer of polycationic species and water-soluble polymers, and

The present invention is directed to a macrocapsule for encapsulating microcapsules containing biologically active material, such as living cells or free living cells, to make the system more biocompatible by decreasing the surface area and surface roughness of microencapsulated biological materials; increasing mechanical stability of microencapsulated biological materials; enhancing cytoprotectivity by increasing diffusion distance of encapsulated biological material from cytotoxins secreted in vivo; providing retrievability of microencapsulated material; and providing a system of sustained release of the cellular products. The method for producing such a macrocapsule containing the microcapsules is also disclosed.

Method for making cytoprotective, biocompatible, retrievable

Microencapsulation of cells

Cytoprotective, biocompatible, retrievable macrocapsule containment

In accordance with the present invention, there are provided methods to render cells non-adhesive and/or non-immunogenic with respect to macromolecules typically encountered in culture media or in physiological media. The invention method comprises contacting cells with an effective amount of a composition comprising a polycationic species having water-soluble polymer chains grafted thereon.

Graft copolymers of polycationic species and water-soluble polymers, and

Crosslinked biocompatible compositions comprising an ionically crosslinked component and a covalently crosslinked component for encapsulating biologics are disclosed. In accordance with the present invention, also disclosed are crosslinkable biocompatible mixtures comprising an ionically crosslinkable component and a covalently crosslinkable component. Methods for encapsulating biologics with the crosslinked and cross-linkable biocompatible compositions are provided. Also, retrievable macrocapsules for encapsulating microcapsules or biologics are disclosed.

Process for encapsulating biologics using crosslinkable biocompatible

Crosslinked biocompatible compositions comprising an ionically crosslinked component and a covalently crosslinked component for encapsulating biologics are disclosed. In accordance with the present invention, also disclosed are crosslinkable biocompatible mixtures comprising an ionically crosslinkable component and a covalently crosslinkable component. Methods for encapsulating biologics with the crosslinked and crosslinkable biocompatible compositions are provided. Also, retrievable macrocapsules for encapsulating microcapsules or biologics are disclosed.

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Los Angeles, CA, United States of America

Roswitha E Heintz