Baxter International Inc.

The Ohio State University

Cryopharm

Gambro, Inc.

The Ohio State Research Foundation

Caridianbct Biotechnologies, LLC

Credit Managers Association of California

Matthew Stewart Platz

Raymond P Goodrich, Jr

Nagender Yerram

Samuel O Sowemimo-Coker

Sang Chul Park

Brian M Aquila

Raymond Paul Goodrich, Jr

Victoria A Wong

Raymond P Goodrich

Roger W Hackett

Helena M Pereira

Christopher B Martin

Nagendar Yerram

Marjan Van Borssum Waalkes

Christine M Williams-Hughes

Shashi S Kagan

Tongqian Chen

This invention is directed towards a method of using visible light at wavelengths of at least 500 nm and above in combination with a sensitizer having a flavin moiety to reduce any pathogens that may be contained in blood and blood components. By exposing the blood and blood components to light of 500 nm and higher, only the sensitizer that is bound to nucleic acids of the pathogens will be activated, thus destroying the sensitizer-pathogenic nucleic acid complex. Because unbound sensitizer is not activated at this wavelength, damage to blood and blood components caused by photolysis of unbound sensitizer may be avoided.

Use of visible light at wavelengths of 500 to 550 nm to reduce the number of pathogens in blood and blood components

Cell preparations comprising a plurality of apoptotic EBV-transformed B lymphocytes and methods of producing cell preparations comprising a plurality of apoptotic EBV-transformed B lymphocytes. The methods comprise transforming B lymphocytes with EBV, incubating the transformed B lymphocytes with a flavin N-oxide photosensitizer, adding a non-toxic antioxidant, and exposing the lymphocytes to an activator, such as photoradiation of an appropriate wavelength to activate the photosensitizer. Also provided are methods of using the apoptotic EBV-transformed B lymphocyte cell preparations to elicit production of EBV-specific T cells in human patients. Finally, methods of treating organ transplant patients, specifically children, comprising administering an effective amount of the apoptotic EBV-transformed B-lymphocyte cell preparation to the patient prior to transplantation are provided.

Apoptotic EBV-transformed lymphocytes, a therapeutic agent for post-transplant lymphoproliferative disorder

Compounds comprising flavin N-oxides for treatments of solid tumors, non-solid tumor masses, leukemias, and non-small cell lung cancers and for eradicating contaminants in blood products. Methods of treating patients having solid type cancers comprising administering a therapeutically effective amount of a flavin N-oxide to a subject in need of treatment and exposing the flavin N-oxide to an activator such that activation of the flavin N-oxide results in damage to the DNA in the cancer cells without substantial damage to the DNA of normal cells are also provided. Methods of using a flavin N-oxide as part of a combination therapy with chemotherapy, radiation therapy, or both are also provided. Methods of reducing pathogenic bacterial or viral contamination in a composition comprising a) mixing the composition with an efficacious amount of a flavin N-oxide and b) exposing the mixture of the composition and the flavin N-oxide to an activator for a period of time sufficient to activate the flavin N-oxide such that the flavin N-oxide reduces the contamination in the composition are also provided. Preferably, the composition is a blood product selected from plasma, platelets, and red blood cells and the activator is an enzyme.

Flavin N-oxides: new anti-cancer agents and pathogen eradication agents

Methods are provided for neutralization of microorganisms in fluids or on surfaces. Preferably the fluids contain blood or blood products and comprise biologically active proteins. Preferred methods include the steps of adding an activation-effective amount of a microorganism neutralizer with an isoalloxazine backbone to a fluid and exposing the fluid to a triggering event. Preferred triggering events include light of a suitable wavelength and intensity to activate the microorganism neutralizer or a pH sufficient to activate the microorganism neutralizer. Other fluids, including juices, water and the like, may also be decontaminated by these methods as may surfaces of foods, animal carcasses, wounds, food preparation surfaces and bathing and washing vessel surfaces. Compounds with an isoalloxazine backbone are also provided.

Isoalloxazine derivatives to neutralize biological contaminants

Viral and bacterial contaminants present in biological solutions are inactivated by mixing one of a novel class of photosensitizer with said solution and irradiating the mixture. Quinoline and quinolone compounds are useful as photosensitizers in this method. With certain photosensitizers a blocking agent may also be employed.

Method of inactivation of viral and bacterial blood contaminants

A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers, frozen or freeze-dried, and irradiated with, for example, UV, visible, gamma or X-ray radiation while in the solid state.

Viral and bacterial contaminants present in biological solutions are inactivated by mixing one of a novel class of photosensitizer with said solution and irradiating the mixture.

Viral, bacterial and parasitic contaminants in blood and cell culture containing compositions are inactivated by adding a photosensitizer and a blocking agent to the composition and irradiating the resulting mixture with electromagnetic radiation. Blocking agents reduce photolysis of the photosensitizer by mechanisms not involving the quenching of reactive oxygen species. The blocking agents reduce photolysis which occurs by ring opening. Preferred photosensitizers are quinoline or quinolone.

The present invention relates to novel, halogenated psoralen compounds that are useful for inactivating vital contaminants in blood-derived products, particularly blood-derived products that contain platelets or red blood cells. The psoralen compounds of the present invention have the following formula: The side chain S which is a attached to the carbon at position 8 of the psoralen moiety contains a quartemary ammonium group which comprises a central nitrogen atom, a linking group L, and an aromatic ring structure. The linking group L joins the central nitrogen atom of the quartenary ammonium group to the psoralen moiety. The linking group L comprises a carbon chain having 2 to 12 carbon atoms and an oxygen atom which links the carbon chain to the psoralen moiety. The psoralen compounds of the present invention also comprise one or more halogens attached to the psoralen moiety. Preferably the halogens are attached to the carbon atom at position 3 or 5 of the psoralen moiety. In one class of these novel psoralen compounds, the central nitrogen atom of the quartenary ammonium group is a component of the aromatic ring structure. In another class, the central nitrogen atom is attached to three substituent groups, R.sup.1, R.sup.2, and R.sup.3 wherein R.sup.3 has the following structure: --R.sup.5 --CH.dbd.CH--R.sup.6 wherein R.sup.5 is a carbon chain comprising 1 to 3 carbon atoms, and wherein R.sup.6 is the aromatic ring, The present invention also relates to methods of making and using the novel psoralen compounds.

Psoralen sensitizers for viral inactivation

A compound is provided for inactivating viral, bacterial or other contamination in cells, body fluids or fractions thereof. The compound comprises a psoralen with a single substituent that is either a quaternary phosphonium or ammonium moiety, and at least one substituent that is a halogen. The compound selectively binds to the contaminant, and upon activation by irradiation, damages the contaminant.

A method for photoinactivating viral and/or bacterial contaminants in blood, blood products or cell cultures is presented. The blood, blood product or cell culture is mixed with an halogenated coumarin sensitizer and irradiated with UV light to inactivate the viral and/or bacterial contaminants.

Photoinactivation of viral and bacterial blood contaminants using

A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers and irradiated with, for example, UV, visible, gamma or X-ray radiation. In particular, quaternary ammonium or phosphonium substituted, halo-psoralen compounds are described as being useful.

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Columbus, OH, United States of America

Matthew Stewart Platz