Novartis Ag

Magenta Therapeutics, Inc.

The Scripps Research Institute

Irm LLC

Fred Hutchinson Cancer Center

Fred Hutchinson Cancer Research Center

Michael P Cooke

Anthony Boitano

Anthony E Boitano

Rahul Palchaudhuri

Ben Wen

Peter G Schultz

Matthew T Burger

Shifeng Pan

Yongqin Wan

Tetsuo Uno

Xing Wang

Bernhard Hubert Geierstanger

John Tellew

Yunho Jin

Kathrin Tissot

Siew Ho Schleyer

Catrin Finner

Susan E Cellitti

Dwight Morrow

Adam Hartigan

Megan D Hoban

Kevin A Goncalves

Si Tuen Lee-Hoeflich

HongNgoc Thi Pham

Patrick C Falahee

Tom Yao-Hsiang Wu

Shailaja Kasibhatla

Jacob Glanville

Irwin D Bernstein

Bradley R Pearse

Sean McDonough

Rajiv Panwar

Colleen Delaney

Andrew T Miller

Karsten Sauer

Tim Wiltshire

Lisa Tarantino

Colin Fletcher

Claire Louise Holness

Oksana Ivanivna Sirenko

The present invention provides antibody drug conjugates, wherein an antibody or antibody fragment that specifically binds to human cKIT is linked to a drug moiety, optionally through a linker. The present invention further provides pharmaceutical compositions comprising the antibody drug conjugates; and methods of making and using such pharmaceutical compositions for ablating hematopoietic stem cells in a patient in need thereof.

Antibody drug conjugates for ablating hematopoietic stem cells

The invention provided herein includes pharmaceutical compositions comprising a TLR7 agonist having the structure of Formula (A), aluminum-containing particles, and one or more pharmaceutically acceptable excipient. The invention further provides the use of such compositions in the treatment of solid tumors either alone or in combination with one or more additional pharmaceutical compositions.

Compounds and compositions for treating solid tumors by intratumoral administration

The invention provides compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a donor, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the compositions and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various stem cell disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. In certain embodiments, the compositions and methods described herein lead to the mobilization of a population of CD34cells that have immunosuppressive effects and that can reduce the incidence of graft vs. host disease.

Dosing regimens for the mobilization of hematopoietic stem and progenitor cells

The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.

Compositions and methods for the depletion of CD117+ cells

The invention provides methods of preventing and treating graft-versus-host-disease and autoimmune diseases, such as those arising from transplant therapy, by selective depletion of hematopoietic cells through the use of antibody-drug conjugates and ligand-drug conjugates that specifically bind CD137. The compositions and methods described herein can be used to treat a variety of pathologies, including stem cell disorders and other blood conditions.

Compositions and methods for the depletion of CD137+ cells

Described herein are compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a subject, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the composition and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

Dosing regimens for the mobilization of hematopoietic stem cells

The present invention relates to methods, kits and compositions for expansion of hematopoietic stem/progenitor cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. Also provided herein are methods for expanding the hematopoietic stem/progenitor cells using kits and compositions comprising a Notch agonist and an aryl hydrocarbon receptor antagonist. The hematopoietic stem/progenitor cells expanded using the disclosed kits, compositions and methods include human umbilical cord blood stem/progenitor cells, placental cord blood stem/progenitor cells and peripheral blood stem cells. The present invention also relates to administering hematopoietic stem/progenitor cells expanded using a combination of a Notch agonist and an aryl hydrocarbon receptor antagonist to a patient for short-term and/or long-term in vivo repopulation benefits.

Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells

The present invention relates to compounds and compositions for expanding the number of CD34+ cells for transplantation. The invention further relates to a cell population comprising expanded hematopoietic stem cells (HSCs) and its use in autologous or allogeneic transplantation for the treatment of patients with inherited immunodeficient and autoimmune diseases and diverse hematopoietic disorders to reconstitute the hematopoietic cell lineages and immune system defense.

Compounds that expand hematopoietic stem cells

Method for expanding hematopoietic stem cells

This invention provides novel methods and compositions for modulating T cell differentiation and T cell responses. The modulators are identified by screening test compounds for ability to modulate an inositol 1,4,5-trisphosphate 3-kinase (IP3K). The IP3K modulators can be further examined for their activity in modulating development of progenitor T cells (e.g., CD4/CD8double positive T cells) into mature CD4or CD8single positive T cells. Pharmaceutical compositions comprising these T cell modulators can be administered to a subject to modulate T cell immune responses, to suppress inflammations, and to treat disease conditions such as autoimmune diseases, graft rejection or allergies.

Methods and compositions for modulating T lymphocytes

The present invention provides three novel HSC genes designated SCM 3, SCM 26, and SCM 113, the coding regions thereof, the gene products, applications of the genes, DNA constructs, vectors and transformed cells each comprising the gene of a fragment thereof. Methods of using the SCM 3, SCM 26 and SCM 113 polynucleotide and polypeptide sequences are also disclosed.

Genes in the control of hematopoiesis

Growing community of inventors

Brookline, MA, United States of America

Michael P Cooke