CellCyte Genetics Corporation recently announced that US Patent No 7,282,222 was issued, a patent which they have exclusive rights to. The press release states that the patent covers unique methods and compositions “to deliver and direct stem cells to target organs in the body”, including cardiac tissue.

The focus of the patent addresses cell retention at a site after delivery – a very important area of cell therapy, especially as it relates to cardiac applications. While no one really knows how cells work therapeutically, it is a good bet that getting more efficient delivery to a site, with minimal biodistribution (ie. keeping the cells at the place where you want them to work), should have an enhanced therapeutic outcome regardless of mechanism. There have been some very good studies quantifying cell retention, notably by Dr. Keith March at Indiana University. Dr. March showed that even via direct injection into the muscle only 10% of the cells remained in the heart after 1 hour, while intravenous injection led to only 1-2% engraftment. In September of 2006, several clinical studies were published in the New England Journal of Medicine concluding that stem cell therapy for cardiac regeneration was mildly efficacious at best. When I read those studies, I felt like the lack of clinical benefit was a result of an unfinished process – cell delivery and retention at the regeneration site had never been optimized or addressed by the people doing the studies. The NEJM studies all had cells delivered via the blood stream and not via direct injection in the heart muscle. There were reports that cells alone don’t work for cardiac regeneration. My gut feeling is that the cells do work, but the cell delivery and retention are completely inefficient. Taking all of this into context, technologies making cell delivery more robust and reproducible are advantageous, especially as it relates to cardiac regeneration.

I went and looked up CellCyte’s recently issued patent (#7,282,222 ) to see evaluate the strength of the claims. One of my favorite downtime activities at work is looking through patent claims, some thing I would recommend to anyone not familiar with patents. I have to say that the claims aren’t too bad, unless you were basing your entire business on this one patent. The patent covers methods for first administering a sticky substance (asialoorosomucoid or orosomucoid) to a patient that would preferentially stick to the organ vasculature of choice, and then administering stem cells (CD34+ or MSCs) via infusion that will then go and adhere to said sticky substance while passing through the blood stream of the tissue – thus ‘targeting’ to the organ of choice (liver and heart are covered in this application).

There are both pros and cons to this patent, from my point of view:

Pros:

· Any issued claims are good – you need a leg to stand on when it comes to intellectual property, and this patent serves the basic purposes

· The issued patent provides freedom to exclude anyone from using the specific sticky substances (asialoorosomucoid or orosomucoid) for targeting stem cells to certain organs

· Data in the patent demonstrates that they do enhance cell engraftment by ~80% (I read this as almost 2X control, not 80% engraftment which would be much better)

Cons:

· The research was not early enough to cover any ‘sticky substance’ for homing of cells or drugs to tissues. The broadest claim possible would read something like: “a method to deliver a therapeutic substance to a desired site via a molecule that adheres to target organ and captures the therapeutic agent from the blood stream” – so there must be prior art in this space

· Claims do not cover the composition of the mucoids or the stem cells mentioned in the patent (composition claims are much stronger than method claims)

· Different sticky substances could be easily discovered via phage display or other technologies which could quickly get around this patent (my friends at Affinergy could figure this out pretty quickly if they wanted to)

· The patent is completely dependent on having access (called Freedom to Operate in the patent world) to stem cells as well as the mucoids needed to practice the covered methods

· While data in the patent shows they can get more cells to a desired site, they do not show any data suggesting that more cells have a therapeutic benefit. It is possible that this technology gets more cells to a specific location but does not allow them to be therapeutically ‘available’

CellCyte seems to be moving this technology forward, and they state on their website that they will initiate a Phase I cardiac trial using CD34+ cells isolated using a CliniMACS device. Interestingly, Baxter is already running a Phase III trial with CD34+ cells isolated using their Isolex device, so CellCyte will be several years behind and will need to have more than incremental improvements to the therapy to justify the costs of a Phase III trial, as well as the development costs associated with bringing a product to market.

CellCyte’s cell targeting ‘product’ looks more like an enabling technology than a stand alone therapy unless CellCyte is able to gain access to their own proprietary cell type. CellCyte seems to be in the licensing mode, so if the right patents come their way they will likely scoop them up and integrate them into their overall strategy – as they have with 3D bioreactors for expanding cells prior to transplantation (although it is unclear where this fits into their overall strategy – which must stil bel under development).

The initial Phase I trial will be important for generating initial safety data on the method, and hopefully some efficacy with their sticky stem cell targeting molecules. As they wait for this data, they will have time to work through their strategy for what cells they will take through clinical trials, and define what their product will actually be – a targeting molecule or a complete therapeutic solution.