University of British Columbia

Chemokine Therapeutics Corporation

Inflazyme Pharmaceuticals Ltd.

The Governors of the University of Alberta

British Canadian Biosciences Corp

Other

Chemokine Therapeutic Corporation

Hassan Salari

Ahmed Merzouk

Geeta Saxena

Christopher R Tudan

Yaping Shen

David L Burgoyne

Edward Piers

John M Langlands

Christine Rogers

Robert Bittman

Ian Clark-Lewis

Joseph H-l Chau

Connie J Eaves

Jiang-Hong Gong

Vincent Duronio

Donald Wong

Lakhdar Arab

Carolina Abramovich

Johanne Cashman

Abdelkrim Habi

Joseph H L Chau

Nick Cheng

Mary A Richter, Legal Representative

Michael Clark-Lewis, Legal Representative

The present disclosure generally teaches compositions comprising SDF-1 mimetics and methods of using them to modulate an activity of a cell having an SDF-1 receptor by binding the SDF-1 receptor to an SDF-1 mimetic. The cell can be a hematopoietic cell, for example, and can be selected from a group consisting of hematopoietic stem cells, hematopoietic progenitor cells, primitive granulocytes, primitive erythroid cells, leukocytes, and neutrophils. In some embodiments, the activity can include the rate of multiplication of the cell or, where the cell is a quiescent cell, the binding can repress the activation of the quiescent cell. Other embodiments of the present invention are taught herein.

Chemokine mimetics synthesis and their use

The present disclosure teaches analogs of human chemokines and methods of using them in the prevention, treatment, and ameliorization of diseases that can benefit from therapeutic angiogenesis. The teachings are generally directed to compositions comprising SDF-1 mimetics, as well as methods that include the use of SDF-1 mimetics to induce neo-vessel formation. The disclosure also teaches articles of manufacture that can be useful in practicing the methods taught herein.

Cyclic peptides for preserving or enhancing the function of an organ allograft

In accordance with various aspects of the invention, CXCR4 antagonists may be used to treat hematopoietic cells, such as progenitor or stem cells, to promote the rate of cellular multiplication, self-renewal, proliferation or expansion. CXCR4 antagonists may be used therapeutically to stimulate hematopoietic stem/progenitor cell multiplication/self-renewal.

CXCR4 antagonist treatment of hematopoietic cells

In accordance with various aspects of the invention, CXCR4 agonists, including SDF-1 polypeptides and SDF-1 polypeptide homologues, may be used in reducing the rate of hematopoietic cell multiplication. Methods of the invention may comprise administration of an effective amount of an CXCR4 agonist to cells selected from the group consisting of hematopoietic stem cells and hematopoietic progenitor cells. Cells may be treated in vitro or in vivo in a patient. A therapeutically effective amount of the CXCR4 agonist may be administered to a patient in need of such treatment. Patients in need of such treatments may include, for example patients requiring bone marrow or peripheral blood stem cell transplantation.

CXC chemokine receptor 4 agonist peptides

Cyclic peptides for modulating growth of neo-vessels and their use in therapeutic angiogenesis

The invention provides a variety of therapeutic uses for CXCR4 antagonists. In various embodiments, CXCR4 antagonists may be used as therapeutically as follows, or to manufacture a medicament for such therapeutic treatments: reducing interferon gamma production by T-cells, treatment of an autoimmune disease, treatment of multiple sclerosis, treatment of cancer, inhibition of angiogenesis. The invention provides corresponding methods of medical treatment, in which a therapeutic dose of a CXCR4 antagonist is administered in a pharmacologically acceptable formulation. Accordingly, the invention also provides therapeutic compositions comprising a CXCR4 antagonist and a pharmacologically acceptable excipient or carrier. The CXCR4 antagonists for use in the invention may be peptide compounds comprising a substantially purified peptide fragment, modified fragment, analogue or pharmacologically acceptable salt of SDF-1.

Methods of treating autoimmune diseases comprising administering CXCR4 antagonists

The present invention is concerned with chemokine analogs, including IL-8 analogs, IP-10 analogs, MIP-1&#x3b1; analogs, RANTES analogs, I-309 analogs, MCP-1 analogs, and CCL28 analogs, that are useful for the treatment of a variety of diseases and disorders, and as an adjunct to the treatment of a variety of diseases and disorders. A therapeutically effective amount of the chemokine analog may be administered to a patient in need of such treatment.

Chemokine analogs for the treatment of human disease

Steroid compounds having various oxygen substitution on the steroid nucleus are disclosed. A specific functionality present on many of the steroid compounds is oxygen substitution at both of positions 6 and 7. Thus, certain steroids have oxygen substitution at C6 and C7, and some have specific stereochemistries such as 6&#x3b1; and 7&#x3b2; oxygen substitution, and an alpha hydrogen at the 5 position in addition to having 6&#x3b1; and 7&#x3b2; oxygen substitution. Steroids having 3,4-epoxy functionality are also disclosed. In addition, steroids having C17 pyran and &#x3b4;-lactone functionality, with oxygen substitution at C6 and C7, or at C15, of the steroid nucleus, are disclosed.

6,7-Oxygenated steroids and uses related thereto

Therapeutic chemokine receptor antagonists

In various aspects, the invention provides compounds that bind to one or more RANTES receptors for the treatment of chemokine mediated disease states, such as compounds of formula (I):

Tricyclic rantes receptor ligands

Steroid compounds having various oxygen substitution on the steroid nucleus are disclosed. A specific functionality present on many of the steroid compounds is oxygen substitution at both of positions 6 and 7. Thus, certain steroids have oxygen substitution at C6 and C7, and some have specific stereochemistries such as 6&agr; and 7&bgr; oxygen substitution, and an alpha hydrogen at the 5 position in addition to having 6&agr; and 7&bgr; oxygen substitution. Steroids having 3,4-epoxy functionality are also disclosed. In addition, steroids having C17 pyran and &dgr;-lactone functionality, with oxygen substitution at C6 and C7, or at C15, of the steroid nucleus, are disclosed.

6, 7-oxygenated steroids and uses related thereto

The invention provides therapeutic and biological uses of chemokine-receptor-binding compounds including uses in the treatment of disease states mediated by chemokines. The relevant chemokines may for example be monocyte chemoattractant protein-one (MCP-1) or interleukin-8 (IL-8), and the relevant chemokine receptors may for example be corresponding chemokine receptors (CCR-2, CCR-4, CXCR-1, and CXCR-2). In one aspect, the invention provides for the use of phenanthrene-9,10-dione in the treatment of multiple sclerosis.

Therapeutics for chemokine mediated diseases

The invention provides therapeutic and biological uses of chemokine-receptor-binding compounds (including chemokine receptor ligands such as chemokine receptor agonists or antagonists), such as naphthoic acid derivatives, including uses in the treatment of disease states mediated by chemokines. The relevant chemokine may for example be stromal cell-derived factor (SDF)-1, and the relevant chemokine receptors may for example be corresponding chemokine receptor (CXCR-4). In other aspects, the invention provides corresponding pharamaceutical compositions and therapeutic methods. In one aspect, for example, the invention provides for the use of 3-Hydroxy-2-naphthoic acid in the treatment of disease.

Bicyclic aromatic chemokine receptor ligands

The invention provides therapeutic and biological uses of chemokine-receptor-binding compounds (including chemokine receptor ligands such as chemokine receptor agonists or antagonists), such as benzopyrone derivatives, including uses in the treatment of disease states mediated by chemokines. The relevant chemokine may for example be interleukin-8 (IL-8), and the relevant chemokine receptors may for example be corresponding chemokine receptors (CXCR-1 and/or CXCR-2). In other aspects, the invention provides corresponding pharamaceutical compositions and therapeutic methods. In one aspect, for example, the invention provides for the use of &lsqb;7-&lsqb;benzopyrone-5&prime;(3&prime;-amino)-thiazole&rsqb;-phenylalanine-benyl ester in the treatment of disease.

Growing community of inventors

Delta, Canada

Hassan Salari