The Johns Hopkins University

Massachusetts Institute of Technology

Tokitae LLC

Stephany Yi Tzeng

Jordan J Green

Ron B Shmueli

Joel Chaim Sunshine

Lowell L Wood, Jr

Robert Samuel Langer

Thanh Duc Nguyen

James J Norman

Ana Jaklenec

Philip A Welkhoff

Boris Nikolic

Kevin McHugh

Nupura S Bhise

William Henry Gates, Iii

Aleksander S Popel

Robert S Langer, Jr

Kristen Lynn Kozielski

Randall A Meyer

Kelly Rhodes

Jayoung Kim

Jamie Spangler

Jakub Tomala

Derek VanDyke

Giorgio Raimondi

William Gates

Marcos Iglesias Lozano

Kristen Kozielski

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

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

Emulsion-based and micromolded ('MM') or three dimensional printed (“3DP”) polymeric formulations for single injection of antigen, preferably releasing at two or more time periods, have been developed. Formulations are preferably formed of biocompatible, biodegradable polymers. Discrete regions encapsulating antigen, alone or in combination with other antigens, adjuvants, stabilizers, and release modifiers, are present in the formulations. Antigen is preferably present in excipient at the time of administration, or on the surface of the formulation, for immediate release, and incorporated within the formulation for release at ten to 45 days after initial release of antigen, optionally at ten to 90 day intervals for release of antigen in one or more additional time periods. Antigen may be stabilized through the use of stabilizing agents such as trehalose glass. In a preferred embodiment for immunization against polio, antigen is released at the time of administration, and two, four and six months thereafter.

Micromolded or 3-D printed pulsatile release vaccine formulations

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

Emulsion-based and micromolded ('MM') or three dimensional printed ('3DP') polymeric formulations for single injection of antigen, preferably releasing at two or more time periods, have been developed. Formulations are preferably formed of biocompatible, biodegradable polymers. Discrete regions encapsulating antigen, alone or in combination with other antigens, adjuvants, stabilizers, and release modifiers, are present in the formulations. Antigen is preferably present in excipient at the time of administration, or on the surface of the formulation, for immediate release, and incorporated within the formulation for release at ten to 45 days after initial release of antigen, optionally at ten to 90 day intervals for release of antigen in one or more additional time periods. Antigen may be stabilized through the use of stabilizing agents such as trehalose glass. In a preferred embodiment for immunization against polio, antigen is released at the time of administration, and two, four and six months thereafter.

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

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

Baltimore, MD, United States of America

Stephany Yi Tzeng