Advanced Photodynamic Technologies, Inc.

Rakuten Medical, Inc.

Aspyrian Therapeutics Inc.

Advanced Photodynamics Technologies, Inc.

Merrill A Biel

Kyle S Johnston

Andreas Rose

Steven H Mersch

Roger Heim

Miguel Garcia-Guzman

Ronald R Zimmermann

Provided herein are conjugates, compositions and methods for use in photoimmunotherapy, such as photoimmunotherapy induced by activation of a phthalocyanine dye conjugated to a targeting molecule that binds a protein on cell, for example, an IR700-antibody conjugate. In some embodiments, the phthalocyanine-dye conjugate can be activated by irradiation with near-infrared light. Features of the conjugates, compositions and methods, including the dose of the conjugate, provide various advantages, such as lower toxicity and/or improved efficacy. In some embodiments, also provided is a dual label phthalocyanine-dye conjugate in which the targeting molecule is conjugated to an additional fluorescent dye, which can be used for photoimmunotherapy while, for example, also exhibiting improved performance for imaging or detection. Also provided are therapeutic methods using the conjugates and compositions for treatment of diseases and conditions, including tumors or cancers.

Compositions, combinations and related methods for photoimmunotherapy

The present invention provides a frontal light diffusing device comprising a non-circular core fiber section having a proximal end and a distal end, and a lens; wherein fiber core of the non-circular core section has a 'top hat' core irradiance distribution and the frontal light diffusing device provides a 'top hat' spatial irradiance distribution at a targeted location. The present invention further provides a frontal light diffusing device comprising an optical fiber and a collimation lens assembly wherein the collimation lens assembly includes a variable aperture that blocks portions of light outcoupled from the optical fiber thereby allowing only a central portion of the light to exit through the variable aperture resulting in a flat irradiance distribution.

Frontal light diffusing device for use in photoimmunotherapy

The present invention provides a diffuser light blocking device comprising an end cap member () having a pocketing feature () that has a side wall () and an end reflective surface (); the pocketing feature's shape corresponds to exterior shape of distal portion () of a diffuser () having a distal end surface (); the pocketing feature engages the distal portion; an overlapping section () of the pocketing feature's side wall surrounds the distal portion's side wall () and prevents at least 95% of the light output from the distal portion from escaping out of the distal portion's side wall; the end reflective surface blocks any forward propagating light output from the distal end surface and returns at least 80% of light coming out of the distal end surface back towards the diffuser; the end cap member is thermally conductive; the end cap member's length () and diameter () provide an exterior surface area that is at least 1,000% of the surface area of the distal end surface; and the device reduces generation of diffuser irradiance hot spots.

Light diffusing devices for use in photoimmunotherapy

The present invention provides a cylindrical light diffusing device comprising a non-circular core fiber having (i) a fiber core that provides a 'top hat' core irradiance distribution; (ii) light blocking means that prevent frontal light emisson from distal end of the non-circular core fiber; and (iii) a light diffusing section having a diffusing proximal end, a diffusing distal end, and internal scattering features distributed within the fiber core of the light diffusing section along central axis of the fiber core, wherein the light diffusion section emits irradiance in a radially symmetric longitudinally 'top hat' diffusing irradiance distribution.

Cylindrical light diffusing device for use in photoimmunotherapy

The invention relates to a method of photoeradication of cellular and acellular organisms including the steps of providing a surface acting agent in association with a cellular or acellular organism, the surface acting agent disorienting a membrane structure so that said membrane no longer functions as an effective osmotic barrier; providing a photosensitive material in association with the cellular or acellular organism; and applying light in association with the cellular or acellular organism to cause a disruption of the organism. The method according to the present invention may be utilized in invitro and invivo treatment protocols for infections, sterilization procedures, cancer cell eradication, virus and fungus eradication, spore eradication, and biofilm organism eradication. Additional aspects of the invention include particular combinations of photosensitive materials and surfactants for use in photodynamic therapies.

Photodynamic cellular and acellular organism eradication utilizing a photosensitive material and surfactant

The invention relates to a method of photoeradication of cellular and acellular organisms including the steps of providing a surface acting agent containing benzalkonium chloride in association with a cellular or acellular organism, the surface acting agent disorienting a membrane structure so that said membrane no longer functions as an effective osmotic barrier; providing a photosensitive material in association with the cellular or acellular organism; and applying light in association with the cellular or acellular organism to cause a disruption of the organism. The method according to the present invention may be utilized in invitro and invivo treatment protocols for infections, sterilization procedures, cancer cell eradication, virus and fungus eradication, spore eradication, and biofilm organism eradication. Additional aspects of the invention include particular combinations of photosensitive materials and surfactants for use in photodynamic therapies.

Photodynamic cellular and acellular organism eradication utilizing a photosensitive material and benzalkonium chloride

A light diffusing device for use in photodynamic therapy has a progressively distally increased exposed amount of core fiber defining a light emitting section. Excessive light energy emission is thus prevented access to proximal locations and provides an increased amount of available light energy at distal locations, thus permitting an even emission of light energy along the light emitting section.

Optical fiber light diffusing device

The invention relates to a method of photoeradication of cells at a tissue site, such as an infection or sterilization site or cancer cell activity site, including applying a solution such as methylene blue, toluidene blue, polymyxin B, SDS, or other surfactants and combinations thereof to the tissue site and exposing the tissue site with a light having a light wavelength and light dosage and a light dosage rate. The solution may have a concentration of methylene blue between 5 &#x3bc;g/ml to about 100 &#x3bc;g/ml. The wavelength may range from about 610 nm to about 670 nm. The light dosage may range from about 0 J/cmto about 200 J/cm. The light dosage rate may range from about 0 mw/cmto about 150 mw/cm. Treatable organisms include, and

Photodynamic therapy utilizing a solution of photosensitizing compound and surfactant

The invention relates to a light emitting treatment device including one or more light members which are configured to emit energy for photodynamic therapy at a treatment field. The treatment device may be made of a polymeric material configured to conform to a body surface. The light members may be disposed in a substantially uniform array and be configured to emit energy in a substantially uniform pattern. The light emitting treatment device may provide light variable feedback to a control apparatus. The light emitting treatment device may further include a heat dissipating layer, a layer of gold or gold alloy, or a layer of adhesive disposed on at least one of the one or more surfaces. Methods of using the treatment device are also disclosed.

Treatment device for topical photodynamic therapy and method of using same

The invention relates to a method of photoeradication of cellular and acellular organisms including the steps of providing a photosensitive material and pyrrolnitrin in association with a cellular or acellular organism and applying light in association with the cellular or acellular organism to cause a disruption of the organism. The method according to the present invention may be utilized in invitro and invivo treatment protocols for infections, sterilization procedures, cancer cell eradication, virus and fungus eradication, spore eradication, and biofilm organism eradication. Additional aspects of the invention include particular combinations of photosensitive materials, pyrrolnitrin, and optional surfactants for use in photodynamic therapies.

Apparatus and method of photodynamic eradication of organisms utilizing pyrrolnitrin

The invention relates to a method of treating an infection or sterilization including applying a dye such as methylene blue, toluidene blue, polymyxin B, or combinations thereof to the area of infection or area to be sterilized and exposing the area of infection or area of sterilization with a light having a light wavelength and light dosage and a light dosage rate. The dye may have a concentration ranging from about 10 &mgr;g/ml to about 500 &mgr;g/ml. The wavelength may range from about 610 nm to about 670 nm. The light dosage may range from about 0 J/cm,to about 200 J/cm,. The light dosage rate may range from about 0 mw/cm,to about 150 mw/cm,. The treatable infections include staphylococcus,,enterococcus, streptococcus,,or,-,The invention also relates to an infection treatment kit.

Dye treatment solution and photodynamic therapy and method of using same

The invention relates to a medical device including a tube and expandable member and one or more light sources disposed in an elongated member disposed in the tube. The light sources emit energy for photodynamic therapy through a window to the treatment area. The treatment device may further include a heat and/or light dissipating layer, such as a layer of gold alloy paint, or other light blocking material.

Expandable treatment device for photodynamic therapy and method of using

A method for differentiating between normal tissue and tumor tissue within a tissue field. The method includes the application of a photosensitizer solution to the tissue field and the subsequent illumination and measurement of fluorescent intensity across the tissue field. The measurement of relative fluorescent intensity across the tissue field provides information relating to the existence or nonexistence of tumor tissue. Solution concentrations of methylene blue and or toluidene blue are utilized to provide the greatest differentiability between normal tissue and tumor tissue within the tissue field.

Methylene blue and toluidene blue mediated fluorescence diagnosis of

A medical apparatus including implantable elongate probes for emitting diffused light energy within the interior of a tissue body to provide a uniform light dosage to the tissue body. In one particular embodiment, the probes may include a plurality of LEDs or VSCEL devices interspaced along the probe shaft. The invention further provides an planar or shaped alignment grid for aligning one or more probes within the tissue body.

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Minneapolis, MN, United States of America

Merrill A Biel