Johns Hopkins University

Asclepix Therapeutics, Inc.

Jordan J Green

Stephany Yi Tzeng

Ron B Shmueli

Aleksander S Popel

Joel Chaim Sunshine

Niranjan B Pandey

Nupura S Bhise

Esak Lee

Randall A Meyer

Jonathan Schneck

Kristen Lynn Kozielski

Kelly Rhodes

Jayoung Kim

Martin Gilbert Pomper

Peter Anthony Campochiaro

Alfredo Quinones-Hinojosa

Gregg L Semenza

Il Minn

Karlo Perica

Jikui Shen

Qiongyu Guo

Eric M Bressler

Anand Kumar

Marcos Iglesias Lozano

Kristen Kozielski

Adam Mirando

Hannah Vaughan

Camila Gadens Zamboni

Alyssa K Galaro

Jamie Spangler

Jakub Tomala

Derek VanDyke

Giorgio Raimondi

Corey J Bishop

John W Hickey

Degradable polymers were synthesized that self-assemble with nucleic acids, proteins, hydrophobic drugs, and other small molecules to form particles that are effective for delivery into a cell, tissue and/or organism either in vitro or in vivo. The presently disclosed polymers demonstrate differential cell-type specificity, an ability to promote endosomal escape to protect the cargos from degradation and enhance delivery to the cytoplasm, and/or bioreducibility, which enables triggered intracellular drug release to be tuned to promote optimal delivery to the target cell type. The presently disclosed materials may be used to treat a wide variety of conditions or diseases, such as cancer, cardiovascular diseases, infectious diseases, and ophthalmic diseases.

Bioreducible poly (beta-amino ester)s for siRNA delivery

The disclosure is directed to a biodegradable particle comprising a polyester or polyester blend, a first protein that binds to an immune cell, and a second protein that promotes proliferation and/or activation of immune cells, and a third soluble protein or small molecule encapsulated within the particle. The second protein is a fusion protein comprising at least a portion of an antibody and at least a portion of a cytokine (i.e., an immunocytokine). The disclosure also is directed to methods for treating a disease or condition in a subject (e.g., an autoimmune disease) comprising administering the aforementioned biodegradable particle to the subject.

Tolerogenic artificial antigen-presenting cells

The present invention provides biodegradable, biomimetic particles for interacting with cells, including immune cells. In various embodiments, the particles comprise a polymer blend comprising a polyester, such as poly(lactic-co-glycolic acid) (PLGA) and a polyamine, such as poly(beta-amino ester) (PBAE). The particles further comprise, on their surface, one or more ligands for one or more cell surface receptor(s) or cell surface molecule(s). In some embodiments, the cell surface receptor or cell surface molecule is on an immune cell, such as a lymphocyte (T cell or B cell), natural killer cell, dendritic cell, or other cell of the immune system or tumor microenvironment.

Biodegradable biomimetic particles

Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure provides significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than commercially available materials, such as LIPOFECTAMINE 2000™, FUGENE®, or polyethylenimine (PEI), for gene delivery to cancerous fibroblasts or human primary fibroblasts. The presently disclosed materials may be useful for cancer therapeutics and regenerative medicine.

Multicomponent degradable cationic polymers

Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed, More particularly, an isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVINF, which exhibits anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumorigenic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models is disclosed. The isolate peptide also exhibits anti-lymphangiogenic and directly anti-tumorigenic properties.

Biomimetic peptide and biodegradable delivery platform for the treatment of angiogenesis- and lymphangiogenesis-dependent diseases

The presently disclosed subject matter provides compositions and methods for administering a nanoparticle or microparticle and a therapeutic agent to the suprachoroidal space in the eye.

Nonviral gene transfer to the suprachoroidal space

A DNA plasmid useful for diagnostic and therapeutic gene therapy is disclosed. Improvements to gene therapy methods known in the art are provided to ensure cancer-targeting, high efficacy, and long durability of expression. The DNA plasmid is combined with compositions of polymeric nanoparticles for non-viral gene therapy to treat cancer, including hepatocellular carcinoma and prostate cancer.

Transcriptionally targeted and CpG-free plasmid for theranostic gene therapy

The present invention in various aspects and embodiments involves pharmaceutical compositions prepared by contacting a candidate &#x3b1;- or &#x3b2;-integrin-binding molecule, or panel thereof, with an integrin heterodimer, and quantifying heterodimer disruption by the candidate molecule. An integrin-binding molecule, or derivative thereof, that disrupts the integrin heterodimer is selected and is formulated into a pharmaceutical composition for administration to a subject, e.g., who has a disease or disorder related to abnormal vascularization.

Methods for identifying and preparing pharmaceutical agents for activating Tie1 and/or Tie2 receptors

The presently disclosed subject matter provides compositions, methods, and kits for transfecting adipose-derived mesenchymal stem cells (AMSCs) in freshly extracted adipose tissue using nanoparticles comprising biodegradable polymers self-assembled with nucleic acid molecules. The presently disclosed subject matter also provides methods for treating a neurological disease in a patient in need thereof, the method comprising administering the AMSCs transfected with the nucleic acid molecules to the patient, wherein the nucleic acid molecules encode one or more bioactive molecules functional in the treatment of a neurological disease, particularly wherein the neurological disease is a brain tumor.

Nanoparticle modification of human adipose-derived mesenchymal stem cells for treating brain cancer and other neurological diseases

Polyethylene glycol (PEG)-b-poly(&#x3b2;-amino ester) (PBAE) co-polymers (PEG-PBAE) and blends of PEG-PBAEs and PBAEs and their use for delivering drugs, genes, and other pharmaceutical or therapeutic agents safely and effectively to different sites in the body and to different cells, such as cancer cells, are disclosed.

Poly(&#x3b2;-amino ester)-co-polyethylene glycol (PEG-PBAE-PEG) polymers for gene and drug delivery

Polymeric nanoparticles, microparticles, and gels for delivering cargo, e.g., a therapeutic agent, such as a peptide, to a target, e.g., a cell, and their use for treating diseases, including angiogenesis-dependent diseases, such as age-related macular degeneration and cancer, are disclosed. Methods for formulating, stabilizing, and administering single peptides or combinations of peptides via polymeric particle and gel delivery systems also are disclosed.

Peptide/particle delivery systems

Mimetic peptides having anti-angiogenic and anti-tumorigenic properties and methods of their use for treating cancer, ocular diseases, such as age-related macular degeneration, and other-angiogenesis-dependent diseases are disclosed. More particularly, an isolated peptide comprising the amino acid sequence LRRFSTAPFAFIDINDVINF, which exhibits anti-angiogenic activity in endothelial cell proliferation, migration, adhesion, and tube formation assays, anti-migratory activity in human breast cancer cells in vitro, anti-angiogenic and anti-tumorigenic activity in vivo in breast cancer xenograft models, and age-related macular degeneration models is disclosed. The isolate peptide also exhibits anti-lymphangiogenic and directly anti-tumorigenic properties.

Compositions and methods comprising asymmetrical artificial antigen presenting cells (aAPCs) are disclosed. The non-spherical aAPCs more closely mimic endogenous cell-cell interactions and can be used for antigen-specific immunotherapy.

Artificial antigen presenting cells having a defined and dynamic shape

The presently disclosed subject matter provides compositions, methods, and kits comprising shape memory particles that can be used for delivering a drug and/or treating a disease or disorder in a patient. Specifically, shape changes in the presently disclosed shape memory particles can be used to control drug delivery spatially and/or temporally in a patient. Also provided are compositions, methods, and kits comprising nanoparticles and hypoxia-inducible factor (HIF) inhibitors with or without chemotherapeutic agents for inhibiting HIF activity in a patient and/or treating a hypoxia-associated disease or disorder.

Shape memory particles for biomedical uses

Degradable polymers were synthesized that self-assemble with DNA to form particles that are effective for gene delivery. Small changes to polymer synthesis conditions, particle formulation conditions, and polymer structure provides significant changes to efficacy in a cell-type dependent manner. Polymers presented here are more effective than commercially available materials, such as LIPOFECTAMINE 2000&#x2122;, FUGENE&#xae;, or polyethylenimine (PEI), for gene delivery to cancerous fibroblasts or human primary fibroblasts. The presently disclosed materials may be useful for cancer therapeutics and regenerative medicine.

Growing community of inventors

Columbia, MD, United States of America

Jordan J Green