W. R. Grace Co.-conn.

Aaron H Heifetz

James A Braatz

Richard A Wolfe

Narender P Luthra

Clifton L Kehr

David M Donofrio

Linda M Custer

Affinity matrices useful for the chromatography and immobilization of biological materials and the method of preparing and using the same are disclosed. The affinity supports are based on hydrated polyurethane polymers which have been activated to provide a means for covalently attaching a variety of bioaffinity agents. The hydrated polymer matrices are characterized by their biocompatibility and resistance to nonspecific protein adsorption. Preferably, the prepolymers used to prepare the hydrated polymers are isocyanate-capped oxyethylene-based diols or polyols, at least 75% of said diols and polyols having a molecular weight of 7000 to about 30,000.

Biocompatible, low protein adsorption affinity matrix

This defined basal nutrient medium is very effective in both high and low density culture of a wide variety of cell lines and cell types. The medium may be used for serum-free culture or supplemented with low levels of serum. The medium contains a buffer system formulated for air equilibration.

Basal nutrient medium for cell culture

Polymer-coated medical and laboratory devices are disclosed which are characterized by their biocompatibility and resistance to nonspecific protein adsorption. The polyurea-polyurethane coatings of this invention are prepared from high molecular weight isocyanate end-capped prepolymers substantially or exclusively comprised of ethylene oxide units. At least 75%, preferably at least 90%, of the prepolymer units are oxyethylene-based diols or polyols having molecular weights of about 7000-30,000, with essentially all of the hydroxyl groups capped with polyisocyanate prior to formation of the hydrated polymer coating.

Protein non-adsorptive polyurea-urethane polymer coated devices

This nutrient medium is very effective for the serum-free or serum-protein-free culture of various animal cells, in both high and low density culture. Serum proteins have been replaced with non-protein-based cell growth enhancers and a non-serum derived protein supplement. The non-protein growth enhancer is a modified or derivatized polyurethane prepolymer of polymer and preferably is a sulfhydryl derivative of polyurethane. The protein supplement may be insulin, an insulin analog or an insulin-like growth factor.

Very low protein nutrient medium for cell culture

Biocompatible polymers derived from isocyanate-capped high molecular weight triols and higher polyols are covalently linked to drugs. These polymer-modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, increased circulating half-life of the drug due to longer residence time in circulation, ability to administer multiple drugs together, and enhanced potency of the drug.

Polymer-modified peptide drugs having enhanced biological and

The cell culturing system of the present invention includes a tubular membrane, e.g. hollow fiber, cartridge. Provision is made for the continuous circulation of a nutrient-containing medium through the tube side of the cartridge by pumping the nutrient-containing medium in an endless loop. The cells to be cultured are placed within the cartridge on the shell side where the desired extracellular products are accumulated. Nutrients are assimilated into the cell culture through the semipermeable tubular membranes and waste products are removed by passing through the semipermeable membranes into the recirculating nutrient-containing medium. Within the endless loop are located a circulating pump, an oxygenator and a pH probe. The system additionally includes a variable delivery feed pump for continuously injecting fresh nutrient-containing solution into the loop, which feed pump is operated at a rate responsive to the measured pH. A portion of the stream exiting the cartridge is continuously split off at a rate identical to that for the introduction for fresh nutrient-containing solution in order to maintain cellular waste products at a suitably low level. The conventional nutrient-solution preparation reservoir has been eliminated from the loop in order to simplify the system and reduce the potential points of entry for contaminating microorganisms. The membrane cartridge is mounted with its longitudinal axis at approximately 60.degree. with respect to the horizontal.

Hollow fiber bioreactor culture system and method

A class of modified hydrophilic prepolymers and polymers is disclosed which are characterized by their specific reactivity. Isocyanate-capped oxyethylene-based prepolymers are modified by reacting with a compound having an isocyanate-reactive group which is a sulfhydryl group, an amino group, a hydroxyl group or a carboxyl group, and a non-isocyanate-reactive group, in quantities sufficient to modify at least a portion of the isocyanate groups of the prepolymer. Where said first functional group is an amino group contained in a diamine or polyamine compound or is a carboxyl group, the modifying compound is present in quantities sufficient to modify all or substantially all of the isocyanate groups of the prepolymer.

Chemically modified hydrophilic prepolymers and polymers

Modified hydrophilic prepolymers and polymers are disclosed wherein the prepolymers and polymers are characterized by cell growth enhancement, and, in some instances, antibody production stimulation. Isocyanate-capped oxyethylene-based prepolymers are modified by reaction with a compound having at least one isocyanate (NCO) reactive group. Preferably, the NCO reactive group is a sulfhydryl group, an amino group or a carboxyl group, in quantities sufficient to modify at least a portion of the isocyanate groups of the prepolymer. The prepolymer and polymer also express a free functional group, preferably an amino, sulfonic acid or a sulfhydryl. When the free functional group is sulfhydryl or sulfonic acid, antibody production stimulation, as well as cell growth enhancement, is observed.

Growing community of inventors

Columbia, MD, United States of America

Aaron H Heifetz