2 stem cell patents issued last week

Dear manoj kumar valluru,

Last week 2 patents of relevance to the area of stem cells were issued.

1. # 7,342,110 (Patent Spotlight), covers composition of matter for antibodies recognizing CD33, a marker found on myeloid committed blood making stem cells.

2. # 7,341,719 how to use myoblast cells for breast augmentation and other types of cosmetic procedures.

In The News

Turning on healthy stem cells, turning off leukemia

Wednesday March 12th, 2008 @ 02:38:49 EST

Sydney, Australia -

The signals that control proliferation of hematopoietic stem cells are still relatively unknown. Not only is the study of the hematopoietic stem cell important because it is one of the most well characterized stem cell systems, but also it has some very strong practical implications in terms of treating disease. For example, hematopoietic toxicity is often the dose-limiting factor in treating cancer with chemotherapy or radiation therapy. Therefore there is great interest in compounds that protect bone marrow stem cells as well as approaches to increase stem cell proliferation One of the interesting ways of stimulating proliferation of hematopoietic stem cells is through inhibiting the enzyme Glycogen Synthase Kinase-3{beta} (GSK-3). Essentially, GSK-3 is involved in degrading beta catenin a stimulator of hematopoietic stem cell proliferation so the idea is that if you inhibit the inhibitor you will get stimulation.

In a recent paper (Holmes et al. Glycogen Synthase Kinase-3{beta} inhibition Preserves Hematopoietic Stem Cell activity and Inhibits Leukemic Cell Growth. Stem Cells. 2008 Mar 6), inhibition of GSK-3 was performed and various molecular pathways where assessed in response to the inhibition using hematopoietic stem cells as a model.

The authors demonstrated that

- inhibition of GSK-3 upregulated expression of HOXB4

- inhibition of GSK-3 resulted in retained LTCIC activity

- inhibition of GSK-3 increased contact between hematopoietic stem cells and the bone marrow stroma

- inhibition of GSK-3 induced apoptosis in leukemia cells, prolly through downregulating survivin

The ability of compounds to turn on healthy hematopoiesis but to kill leukemic hematopoiesis is a very strange phenomena. This is also observed in vitro with valproic acid

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This Week's Patent Spotlight

Anti-CD33 antibodies and method for treatment of acute myeloid leukemia using the same

Patent Number: 7,342,110

Assignee | Inventor

One of the major technological advances that allowed for the characterization and use of stem cells was the development of defined monoclonal antibodies that repeatedly attached to markers on stem cells. For example, the patents covering the original hematopoietic stem cells used monoclonal antibodies to actually identify the cell population that was claimed. Other monoclonal antibodies towards hematopoietic stem cells have subsequently been patented, for example MG-1 by the company Morphogenesis Monoclonal antibodies are also currently under development that target cancer stem cells

The current patent covers the composition of matter for antibodies that bind to CD33. This is a marker of committed myeloid stem cells. These cells do not have the ability to generate lymphoid or megakaryocytic cells but only granulocytes and monocytes. One of the interesting things about this is that in some types of leukemias the leukemic transformation occurs at the committed myeloid progenitor level. So if one was to deplete all the CD33 positive cells, then one could save the early hematopoietic stem cell which is healthy but kill all the leukemic cells which are committed and have CD33 on them. Even in leukemias such as CML, it may be possible to select autologous cells that are more primitive than the “leukemic stem cell". For example, there are some groups (although it is very controversial) who claim to be able to differentiate mesenchymal or mesenchymal-like cells into hematopoietic stem cells. To date, mesenchymal stem cells of patients with CML have not been detected to express the bcr-abl translocation.

Another interesting reason why the current patent is useful is that one may want to collected myeloid precursor cells for allogeneic use after hematopoietic depletion. After patients have chemotherapy there is a need to "re-start” the immune system. Unfortunately this may be difficult in situations where G-CSF does not induce enough granulopoiesis, or induce it rapidly enough to prevent opportunistic infections. The idea would be to administer differentiated progenitors such as CD33 positive cells and hope that they more rapidly generate granulocytes before the patient's own HSC make them. This could be a useful bridge therapy. Nexell had some interesting patents in this area including methods of administering neutrophil precursors to treat neutropenia

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