Methods of cancer therapy targeted against a cancer stem line

Patent Number: 7,361,336

The concept of the cancer stem cell revolves around the notion that 99% of cells making a tumor mass, while deadly, are not the ones that keep the tumor growing.  The <1% of cells of a tumor, which possess unique surface markers and functional activities are the ones that continually cause the tumor to keep growing.  According to this idea, drug development in cancer for the past 50 years has been targeting the wrong cells, since efforts were made at killing the 99% cells and not the tumor stem cell.  This theory is attracting significant interest from the Pharmaceutical and Investment community.  This year GSK entered a deal worth more than a billion dollars with the cancer stem cell company OncoMed, which has no products in the clinic.  The value of the deal was based on patented methods of specifically targeting tumor stem cells.

The current patent also covers a way of inhibiting stem cells, with emphasis on cancer stem cells.  The inventor, Dr Ivan Bergstein, is the CEO of StemLine, a company that recently raised $12 million from VC sources.

Specifically, the patent teaches that antibodies to frizzled have activity against cancer stem cells.  Claims we find important include: "A method of treating cancer comprising administering to a patient diagnosed with cancer an antibody or a fragment thereof that binds to a human homolog of frizzled, in an amount sufficient to inhibit the proliferation of cancer cells in the patient."   This claim effectively blocks others from using any antibody towards frizzled for cancer therapeutics in general.

What is frizzled?

It is a G protein coupled receptor that is part of the developmentally critical wnt pathway.  We imagine that since frizzled is found on various non-malignant stem cells during development, the inventor reasoned that some common components exist between malignant and nonmalignant stem cells, and therefore looked at this protein.  What is interesting is that this patent has the earliest priority date of 1997, almost a decade before publications started appearing describing stem cell markers such as CD133 on tumor stem cells.

Perhaps even more interesting is the fact that a very thorough and in-depth discussion is given regarding cancer stem cells and the theory that the StemLine CEO has about why cancer exists.  This theory is called the OSES ("one-step epigenetic switch") model of carcino-genesis and essentially states that "a clandestine slow-growing relatively mutationally-spared cancer stem line acts as the immortal founder line of a tumor and produces as its progeny the highly proliferative mutant cancer cell populations targeted by conventional therapies mentioned above. Accordingly, it will be shown that this cancer stem line (hypothesized to exist by the OSES model) is not targeted by conventionally-based therapies (designed to target fast-growing largely mutant cells rather than slow-growing non-mutant cells). In this manner, the untargeted cancer stem line can gradually regrow the tumor mass following standard therapy thereby leading to treatment failure and clinical relapse".

If Stemline's other patents and approaches possess a similar excellence to this patent, the company must definately be supported.

View this patent on the USPTO website.

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