Harvard College

Samuel Heath & Sons Plc

Massachusetts Institute of Technology

The Broad Institute, Inc.

Ipsen Pharma S.a.s.

Gw Research Limited

Ipsen Biopharm Limited

Allergan, Inc.

Syntaxin Limited

The Secretary of State for Health

Ipsen Bioinnovation Limited

Keith Foster

John Andrew Chaddock

Philip Marks

Patrick Stancombe

David R Liu

Lance Steward

Joseph Francis

Bradley Lether Pentelute

K Roger Aoki

Colin Stott

R John Collier

Vincenzo Di Marzo

Michael S Packer

Charles Penn

Isaac M Chiu

Lyndsey Durose

Sai Man Liu

Frederic Madec

Matthew Beard

Philip Lecane

Stephen Johnstone

Shilpa Palan

Fabio Iannotti

Travis R Blum

The disclosure provides amino acid sequence variants of Botulinum neurotoxin (BoNT) proteases that cleave (VAMP1, VAMP2, VAMP7, VAMP8, SNAP25, SNAP23, PTEN, etc.) and methods of evolving the same. In some embodiments, proteases described by the disclosure are useful for cleaving proteins found in a cell, that is in an intracellular environment. In some embodiments, proteases described by the disclosure are useful for treating diseases associated with increased or aberrant VAMP7, VAMP8, SNAP23 or PTEN expression or activity, for example, cancer and neurological disorders. Some aspects of this disclosure provide methods for generating BoNT protease variants by continuous directed evolution.

Evolution of BoNT peptidases

Embodied herein are engineered fusion proteins that bind and target nociceptor neurons, compositions comprising these engineered fusion proteins, and methods for treatment of pain using these engineered fusion proteins or compositions containing the engineered fusion proteins. The engineered fusion proteins contain domains derived from protein toxins such as the anthrax toxin, clostridial botulinum family of toxins, disulphide-containing toxins, and AB component type toxins.

Compositions and methods for treatment of pain

The present invention relates to the use of cannabinoids in the treatment of degenerative skeletal muscle disease. In particular the degenerative skeletal muscle disease is Duchenne muscular dystrophy (DMD). Preferably the cannabinoids are one or more of: Cannabidiol (CBD); Cannabidivarin (CBDV); and Tetrahydrocannabivarin (THCV).

Use of cannabinoids in the treatment of degenerative skeletal muscle diseases

A door closer includes an anchor assembly for mounting on a door frame, an actuator assembly for mounting within the thickness of a door which is hinged for movement between open and closed positions, an operating member coupled by a linkage to the anchor assembly and mounted for a range of movements between a retracted position and an extended position, a resilient driving apparatus arranged to exert a driving force on the operating member, a damper mechanism operatively connected to the operating member so as to damp movement of the operating member at least in a direction towards the retracted position, and a resilient thrust device arranged to exert an increased driving force on the operating member over a defined part of its range of movement as the operating member approaches the retracted position.

Door closer

A door closer having a pair of main driving springs, a fluid-filled damper arrangement and a pair of thrust springs is provided, the thrust springs coming into effect during the latter part of a door closing operation, so as to provide an augmented closing force at that point. The position at which the augmented closing force is applied is variable, with a cam mechanism being used to control application of the increased closing force.

Growing community of inventors

London, United Kingdom

Keith Foster