University of Pennsylvania

University of Virginia Patent Foundation

Icahn School of Medicine at Mount Sinai

University of California

The Children's Hospital of Philadelphia

Vladimir R Muzykantov

Douglas B Cines

Juan Carlos Murciano

Abd Al-Roof Higazi

Thomas D Dziubla

Edward Howard Schuchman

Ronald P Taylor

Silvia Muro Galindo

Eric Simone

Robert J Levy

Donald L Siegel

Samir Suresh Mitragotri

Michael Chorny

Elliot S Barnathan

Elizabeth Hood

Carlos H Villa

Jacob Brenner

Silvia Muro-Galindo

Daniel Sebastian Pan

D Neil Granger

Tom Dziubla

Jacob Myerson

Steve M Albelda

Colin Greineder

Sergei V Zaitsev

Bi-Sen Ding

Compositions and methods are provided for loading cargoes onto red blood cells. Provided herein are novel antibodies, fragments, fusion proteins and other conjugates which specifically bind red blood cells via RHCE or Band 3.

Fusion proteins and antibodies targeting human red blood cell antigens

Compositions comprising a red blood cell (RBC) having non-toxically coupled thereto a nanoparticle having a low shear modulus or low Young's modulus of less than 10 MPa and containing a drug are provided. In one embodiment, the nanoparticles are optionally coated with protein. In another embodiment, the nanoparticle has no cell-specific targeting moiety or tissue-specific targeting moiety or organ-specific targeting moiety associated therewith. Methods of delivering selected drugs to target organs use these compositions both in vivo and ex vivo treatment of disease and for imaging.

Methods and compositions for drug delivery

The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.

Targeted carriers for intracellular drug delivery

The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.

Targeted protein replacement for the treatment of lysosomal storage disorders

Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Therapeutic particles can comprise antioxidant enzymes, and can be targeted to cells to protect the cells from oxidative damage.

Uniform field magnetization and targeting of therapeutic formulations

A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.

Method and compositions for polymer nanocarriers containing therapeutic molecules

Fusion proteins comprising a single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.

Targeting recombinant therapeutics to circulating red blood cells

The present invention is a method for encapsulating active protein in a polymeric nanocarrier. The instant method employs homogenization at subzero temperatures so that enzyme activity is retained. Enzymes which can be encapsulated by the present method include, for example, antioxidant enzymes and xenobiotic detoxifying enzymes. Encapsulation of an enzyme protects it from protease degradation and increases therapeutic half-life. Advantageously, polymeric nanoparticles of the invention are permeable to enzyme substrates and therefore enzymes encapsulated by the instant method can exert their effect without release from the nanocarrier. Methods for decomposing a reactive oxygen species, protecting against vascular oxidative stress, and detoxifying a xenobiotic are also provided.

Antioxidant polymer nanocarriers for use in preventing oxidative injury

Compositions and methods for prevention and treatment of uncontrolled formation of intravascular fibrin clots are provided wherein fibrinolytic or anticoagulant drugs are biocompatibly coupled to red blood cell carriers.

Compositions and methods for prevention and treatment of uncontrolled formation of intravascular fibrin clots

Methods for targeting and prolonging association of a selected drug to the luminal surface of pulmonary vascular endothelium of an animal are provided wherein a selected drug is administered to an animal in combination with a non-internalizable ICAM-1 antibody which binds to an antigen on the luminal surface of the pulmonary vasculature. This method is particularly useful in dissolution of fibrin clots or prevention of the intravascular coagulation in the pulmonary vasculature.

Targeting and prolonging association of drugs to the luminal surface of the pulmonary vascular endothelial cells using antibodies that bind to ICAM-1

A method for enhancing intracellular delivery of effector molecules is provided. The method involves modifying selected antibodies with biotin and streptavidin, conjugating these antibodies with an effector molecule, and delivering the conjugated effector to an intracellular target specifically recognized by the antibody.

Growing community of inventors

Warminster, PA, United States of America

Vladimir R Muzykantov