The Brigham and Women's Hospital, Inc.

Harvard College

James Pancoast

Richard Theodore Lee

Francesco Loffredo

Parth Patwari

Zheng Xin Dong

Amy J Wagers

Todd Vannelli

Matthew Steinhauser

Methods and compositions are described for management of the pharmacokinetic properties of active agents, e.g., therapeutic moieties, by conjugating, fusing, or non-direct linkage of the active agent to one or more wild-type or modified heparin-binding peptides (HB). Compounds may be administered to tissues including skin. Contemplated uses include treatment of disease, allergen immunotherapy, and immunization. Other aspects relate to compositions, methods and kits comprising heparin-binding peptides (HB) fused or conjugated to the therapeutic agents.

Compounds and methods for modulating pharmacokinetics

The present invention relates to compositions, methods and kits for delivery of an IGF-1 protein or a functional fragment or variant, derivative thereof to cells or tissues that express proteoglycans. More specifically, the present invention relates to fusion proteins comprising a heparin binding protein (HB) comprising SEQ ID NO: 1 or SEQ ID NO: 2. Other aspects relate to use of a HB-IGF-1 fusion proteins in methods to deliver IGF-1 to the cartilage for the treatment of a cartilage related disease and disorder in a subject.

Selective cartilage therapy

The technology described herein relates to treatments for, e.g., diastolic heart failure, cardiac hypertrophy, and related conditions.

Growth differentiation factor 11 (GDF-11) for treatment of diastolic heart failure

The present invention relates to compositions, methods and kits for delivery of active agents (X) to cells or tissues that express proteoglycans. More specifically, the present invention relates to conjugates comprising (HB-linker)-X-(linker-HB), where HB is a heparin binding protein, X is an active agents such as a therapeutic protein (including a functional fragment or variant thereof), or a therapeutic small molecule, linker is a linker entity and m is an integer of at least 1, and n+o is an integer of at least 1. Other aspects relate to use of a HB-X conjugate in methods to deliver active agents to cartilage for the treatment of cartilage related disease and disorders, the use of the HB-X conjugate in methods to deliver active agents to neuronal tissues (e.g., brain and spinal cord) for the treatment of neurological disorders, and the use of the HB-X conjugates in methods for the treatment of eye conditions and disorders and inflammatory conditions and disorders.

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Cambridge, MA, United States of America

James Pancoast