The Johns Hopkins University

Kala Pharmaceuticals, Inc.

Jie Fu

Justin Scot Hanes

Peter Anthony Campochiaro

Barbara S Slusher

Jin Yang

Jeffrey L Cleland

Samuel K Lai

Laura M Ensign

Donald Jeffrey Zack

Ming Yang

Zhiyong Yang

Cynthia Ann Berlinicke

Derek Stuart Welsbie

Qingguo Xu

Denis Wirtz

Ying-Ying Wang

Walter J Stark

Anne Le

Michelle Rose Dawson

Eric Mark Krauland

Jennifer Fiegel

Olcay Mert

Yun Yu

Joshua Kays

Non-linear multiblock copolymer-drug conjugates for the treatment and prevention of diseases and disorders of the eye are provided. The polymer-drug conjugates can form nanoparticles, microparticles, and implants that are capable of effectively delivering therapeutic levels of one or more active agents for an extended period of time. Administration to the eye of an active agent in the form of a non-linear multiblock copolymer-drug conjugate produces decreased side effects when compared to administration of the active agent alone. Also provided are methods of treating intraocular neovascular diseases, such as wet age-related macular degeneration as well as diseases and disorders of the eye associated with inflammation, such as uveitis.

Non-linear multiblock copolymer-drug conjugates for the delivery of active agents

Methods for increasing the encapsulation or incorporation of Sunitinib into polymeric matrices have been developed. The resulting formulations provide for more sustained controlled release of sunitinib or other inhibitors of JNK signaling, which bind to DLK. Increased loading is achieved using an alkaline solvent system. The pharmaceutical compositions can be administered to treat or reduce neuronal death due to elevated intraocular pressure. Upon administration, the sunitinib or other inhibitor is released over an extended period of time at concentrations which are high enough to produce therapeutic benefit, but low enough to avoid unacceptable levels of cytotoxicity, and which provide much longer release than inhibitor without conjugate.

Sunitinib formulations and methods for use thereof in treatment of glaucoma

Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into 'soluble' colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.

Glutaminase inhibitor discovery and nanoparticle-enhanced delivery for cancer therapy

Controlled release dosage formulations for the delivery of one or more HIF-1 inhibitors are provided. The controlled release formulations contain one or more HIF-1 inhibitors conjugated to or dispersed in a polymeric vehicle. The one or more HIF-1 inhibitors can be dispersed or encapsulated in a polymeric matrix. In some embodiments, the one or more HIF-1 inhibitors are covalently bound to a polymer, forming a polymer-drug conjugate. Polymeric vehicles can be formed into implants, microparticles, nanoparticles, or combinations thereof. Controlled release HIF-1 formulations provide prolonged therapeutic benefit while lowering side effects by releasing low levels of one or more HIF-1 inhibitors and/or HIF-1 inhibitor conjugates over a prolonged period of time. Controlled release dosage formulations can be used to treat or prevent a disease or disorder in a patient associated with vascularization, including cancer, obesity, and ocular diseases such as wet AMD.

Controlled release formulations for the delivery of HIF-1 inhibitors

The invention generally relates to polymeric particles suitable for transporting bioactive agents across mucosal barriers. The invention also relates to methods of making and using those polymeric particles.

Drugs and gene carrier particles that rapidly move through mucous barriers

The present application is directed to biodegradable polymers, compositions, including microspheres and nanospheres, formed of such polymers, and methods of using such polymers and compositions. In certain embodiments, the subject polymer compositions include therapeutic agents, optionally providing sustained release of the encapsulated agent after administration to a patient.

Functionalized poly(ether-anhydride) block copolymers

Biodegradable polymer compositions, compositions and uses related thereto

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Baltimore, MD, United States of America

Jie Fu