University of California

University of Oregon

Aurora Biosciences Corporation

Rakuten Medical, Inc.

Other

Life Technologies Corporation

Fondazione Istituto Italiano Di Technologia

Fondazione Istituto Italiano Di Tecnologia

Roger Heim

Roger Y Tsien

Andrew B Cubitt

S James Remington

Mats F Ormo

Miguel Garcia-Guzman

Mats F Orm&ouml;

Lewis R Makings

Daniele Piomelli

Rita Scarpelli

Merrill A Biel

Marco Migliore

Robert M Dickson

Jerry Fong

Miguel Garcia-Guzmàn

Merrill Biel

William E Moerner

Eileen Sun Chin

Deepak Yadav

Mats F Ormö

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

Provided are methods for manufacturing a conjugate containing a phthalocyanine dye, including methods that include one or more steps of preparing or producing the conjugate, formulating the conjugate and packaging the conjugate. In some aspects, the manufacturing methods result in the generation of a stable conjugate. Also provided are stable phthalocyanine dye conjugates, compositions and articles of manufacture containing the stable conjugates, and methods for their administration to subjects for photoimmunotherapy. In some embodiments, the phthalocyanine dye conjugates are conjugated to a targeting molecule, such as an antibody, that targets the conjugate to a cell or pathogen, such as by binding to a cell surface protein.

Methods for manufacturing phthalocyanine dye conjugates and stable conjugates

Disclosed herein, inter alia, are compositions and methods for modulating the activity of N-acylethanolamine acid amidase for the treatment of a pathological state, including pain, an inflammatory condition, or a neurodegenerative disorder.

Piperazinyl methanone NAAA inhibitors

This invention provides tandem fluorescent protein construct including a donor fluorescent protein moiety, an acceptor fluorescent protein moiety and a linker moiety that couples the donor and acceptor moieties. The donor and acceptor moieties exhibit fluorescence resonance energy transfer which is eliminated upon cleavage. The constructs are useful in enzymatic assays.

Method for determining the presence of an enzyme in a sample

Engineered fluorescent proteins, nucleic acids encoding them and methods of use are provided.

Long wavelength engineered fluorescent proteins

Tandem fluorescent protein constructs

Modifications in the sequence of Aequorea wild-type GFP provide products having markedly different excitation and emission spectra from corresponding products from wild-type GFP. In one class of modifications, the product derived from the modified GFP exhibits an alteration in the ratio of two main excitation peaks observed with the product derived from wild-type GFP. In another class, the product derived from the modified GFP fluoresces at a shorter wavelength than the corresponding product from wild-type GFP. In yet another class of modifications, the product derived from the modified GFP exhibits only a single excitation peak and enhanced emission relative to the product derived from wild-type GFP.

Modified green fluorescent proteins

Engineered fluorescent proteins, nucleic acids encoding them and methods of use.

This invention provides functional engineered fluorescent proteins with varied fluorescence characteristics that can be easily distinguished from currently existing green and blue fluorescent proteins. In one aspect, the invention provides nucleic acids, expression vectors and recombinant host cells comprising nucleotide sequences encoding functional engineered fluorescent proteins comprising aromatic substitutions at position 66 and a folding mutation. In one embodiment the invention provides for fluorescent proteins containing an aromatic substitution at Thr 203.

This invention provides functional engineered fluorescent proteins with varied fluorescence characteristics that can be easily distinguished from currently existing green and blue fluorescent proteins. In one embodiment the invention provides for the three dimensional structure and atomic coordinates of an Aequorea green fluorescent protein and methods for their use. In one embodiment, this invention provides a computational method of modeling the three dimensional structure of any other fluorescent protein based on the three dimensional structure of an Aequorea green fluorescent protein.

Photochromic fluorescent protein moiety having two or more stable states having excitation or emission spectra that are shifted from one wavelength region to another wavelength region in the two states are described. The photochromic material switches between states by irradiation with light of appropriate wavelengths. The two states are preferably stable at room temperature and in the dark. The switching between states can be reversible.

Growing community of inventors

Del Mar, CA, United States of America

Roger Heim