Methods for cell mobilization using in vivo treatment with hyaluronan (HA)

Patent Number: 7,446,100

Stem cell mobilization is important commercially/medically from several angles.  Firstly, donors of hematopoietic stem cells usually prefer to have their bone marrow resident stem cells "mobilized" so as to enter the blood and be collected from blood as opposed to having holes drilled in their iliac crest.  Secondly, for some types of cancer, autologous hematopoietic stem cell transplants are performed.  This involves inducing mobilization of the patient's hematopoietic stem cells into the blood stream, collecting the hematopoietic stem cells, treating the patient with high dose chemotherapy, and subsequently re-infusing the hematopoietic stem cells so as to "rescue" the blood making system of the patient from the high dose chemotherapy bone marrow insult.  The third reason why mobilization is important is that after heart attacks, or strokes, the injured tissues sends out signals that mobilize and chemoattract bone marrow resident stem cells to the damaged myocardium or brain.  There are positive correlations published between extent of mobilization and improved prognosis.  Therefore, mobilizing agents are useful for augmenting this endogenous response to injury process.

The most commonly used mobilizing agent is G-CSF, with several newer ones being clinically developed such as Anormed/Genzyme's Mozobil (CXCR4 antagonist), parathyroid hormone, combinations of FGF and VEGF, and various toll like receptor agonists. 

The current patent provides a new approach to mobilization.  It teaches the use of various molecular weight fragments of hyaluronic acid to induce not only mobilization of stem cells, but also a general increased immune responsiveness through augmenting levels of circulating immunocytes. 

In our opinion, the most powerful claim is the first one, essentially, "A method for treating a patient needing an increase in components of the acquired/adaptive immune response as a result of chemotherapy mediated immune suppression through administration of hyaluronic acid fragments less than 750 kDA." 

The Canadian company Orcrist Bio is developing various embodiments of this patent clinically for treatment of post-chemotherapy immune suppression, amongst other indications.  Given this strong patent position, multibillion dollar established market for post-chemo immune modulators, as well as excellent safety profile of these fragments of hyaluronic acid, expect to see great things come out of Orcrist's HYC 750 product.

View this patent on the USPTO website.