Applied Molecular Transport Inc.

Genentech, Inc.

Trinity Biosystems, Inc.

Children's Hospital Research Center at Oakland

Children's Hospital Medical Center of Northern California

University of California

National Institutes of Health, a Component of the US Dept. of Health & Human Services

University of Chicago

University College Cardiff Consultants Limited

University of Ca

Applies Molecular Transport Inc.

Mcmaster University

Mahmood, Tahir

Mrsny, Randall J.

Thornhill Therapeutics, Inc.

Randall J Mrsny

Tahir Mahmood

Weijun Feng

Sally Rhiannon Postlethwaite

Charles Olson

Thomas Carl Hunter

Sean Dalziel

John Joseph Koleng, Jr

Derek Maclean

Marvin R Garovoy

Deborah Anne Dean

Ben-Quan Shen

Kevin Yin

Bittoo Kanwar

Rajendra Tandale

Jonathan H Widdicombe

Hyojin Kim

Amir Porat

Khushdeep Mangat

David J FitzGerald

Marian L McKee

Ann L Daugherty

Jerrold R Turner

Julia Dawn Mackay

Keyi Liu

Marvin Garovoy

James Andrew Whitney

John Koleng

Alistair Taverner

Elizabeth Bhatt

Elbert Seto

Sally Postlethwaite

Derek Mckay

The present disclosure provides delivery constructs comprising a carrier coupled to a heterologous payload, wherein coupling of the carrier to the payload can result in transportation of the payload (e.g., a therapeutic payload) into and/or across intact polarized epithelial cells (e.g., epithelial cells of the gut of a mammal). The delivery construct can be part of a pharmaceutical composition that can be orally administered to a subject to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases or autoimmune diseases.

Cholix-derived carriers for oral delivery of heterologous payload

Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in the lamina propria of the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

Compositions, formulations and interleukin production and purification

Described herein are cholix-IL-10 fusion proteins, and methods of use thereof, which can be characterized by a distinct response in an individual when administered. This distinct response can comprise changes in levels of one or more markers in the individual and/or co-localization of IL-10 in theof the individual. Further described herein, in some embodiments, are oral formulations of the cholix-IL-10 fusion proteins. Described herein are methods for the purification of an IL-10 delivery construct, including methods for refolding and enrichment, which can result in maintenance of a high percentage of the IL-10 delivery constructs in the biologically active dimer form. Described herein are oral formulations configured for site-specific release of a therapeutic protein in the small intestines or colon. In some cases, the therapeutic protein is in the form of a dimer, such as an IL-10 delivery construct capable of crossing the gut epithelium.

The present disclosure relates to isolated non-naturally occurring delivery constructs comprising a bacterial toxin-derived delivery construct coupled to a biologically active therapeutic cargo; wherein the delivery construct is capable of delivering the biologically active cargo via transcytosis transport across an epithelial cell; and wherein the delivery construct does not comprise a bacterial toxin-derived translocation domain or a bacterial toxin-derived catalytic (cytotoxic) domain.

Toxin-derived delivery constructs for pulmonary delivery

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of theCholix gene (ntCholix), a variant of Cholix truncated at amino acid A(Cholix) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.

Cholix toxin-derived fusion molecules for oral delivery of biologically active cargo

The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

Delivery constructs for transcytosis and related methods

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders.

Growing community of inventors

Los Altos Hills, CA, United States of America

Randall J Mrsny