The IP Factor

WO/1999/004773 titled “Method for Inhibiting Bone Resorption” is a patent application to Merck for a once weekly oral dosage pill for alendronate and other bisphosphonates for the treatment of Paget’s disease and osteoporosis and was filed in Israel as a national stage entry of the PCT as IL 153109.

Alendronate is marketed by Merck as Fosomax®, which has annual worldwide sales of over one billion US dollars.

Once granted, the application was published for opposition purposes, and both Teva and Unipharm, Israel’s leading generic companies opposed the application. We note that Unipharm was responsible for the cancelation of the basic alendronate patent in the Israel Supreme Court. As would be expected, Merck was represented by Richard Luthi, Unipharm by Adi Levit and Teva by Tal Band.

The main claim is as follows:

A pharmaceutical composition useful for inhibiting bone resorption in a human comprising from about 70 mg to about 140 mg of alendronic acid or a pharmaceutically acceptable salt thereof, or a mixture thereof, on an alendronic acid active weight basis, in association with a pharmaceutically acceptable carrier, wherein said composition is adapted for oral administration as a unit dosage form according to a continuous schedule having a periodicity selected from once-weekly dosing and bi-weekly dosing.

The grounds for opposition were lack of novelty, lack of inventive step, lack of utility and non-patentable subject matter. The Commissioner of Patents, Dr Meir Noam, complimented all the expert witnesses, both those recruited locally and those flown in from abroad, for their objectivity and professionalism, and pointed out that he had spent 12 days conducting oral hearings.

In his ruling, Dr. Noam concluded:

1. That a specific formulation indicated for a specific dosage regime was patentable subject matter in Israel, and fell outside the ambit of section 7(i) which excludes methods of treatment of a human from patentable subject matter.
2. Although there were suggestions in the literature – specifically in a professional journal called Lunar – to try administering a higher dosage less frequently, including once a week, as away of overcoming certain side effects, these were insufficient to rule out absolute novelty.
3. The combination of the Lunar references and some of the previously reported filed tests were sufficient to render the invention obvious and lacking in inventive step, since although some of the papers indicated that a higher dosage would cause more gastrological irritation, there was sufficient evidence that the problem was caused by pills sticking in the throat, and so the frequency of dosage was more significant than the size of the dose. This coupled with the well established long half-life of the drug and the Lunar publications actually making the suggestion rendered the idea of reducing the frequency and upping the dose obvious to try. Furthermore, the 70 mg dose and once week administering of the treatment were both found in the literature.
4. Having ruled the claimed invention as lacking in inventive step, the question of utility was moot, so Dr. Noam excused himself from ruling on the hundreds of pages of evidence submitted on the issue by both sides.

One interesting argument, put forward on behalf of Unipharm by Adi Levit, was that Haber’s rule applied, i.e. that  ”the time of exposure makes the poison”. In other words, where the problem is local irritation, a higher dosage for a shorter exposure time is likely to be beneficial, and thus there was no invnetive step. Merck tried to get this argument suppressed on technical grounds, claiming that it wasn’t in the original opposition as filed.

After ruling the patent invalid, the opposers, Teva and Unipharm, were given 30 days to submit breakdowns of costs incurred.

The case: Opposition to IL 153109 to Merck, titled “Pharmaceutical Composition Useful for Inhibiting Bone Resorption in a Human Comprising Alendronic Acid or a Pharmaceutical Acceptable Salt thereof or a Mixture Thereof”.

COMMENT

The decision as to lack of inventive step is clear and correct. We note that the same patent was disallowed in Korea and the UK as relating to a method of treatment, and in Europe as lacking inventive step. Dr. Noam is correct, however, that a decision in Israel should attempt to interprete the local law in light of local precedent, and that the courts and patent office should be aware of but not bound by decisions in corresponding cases in other jurisdictions.

The applicants claimed that Circular MN 30 allows Swiss type claims, i.e. new uses for old treatment, and the claimed invention was directed to a formulation. I tend to side with the opponents though and find the Commissioner’s ruling on this point not convincing. I see this as a patent for a method of treatment where the dosage regime is an inherent part of the treatment, since the product lacks inherent novelty, and the novelty is a function of the dosage, which is a method step. Arguably, however, because of the long half life, the product is the high dosage pill – regardless of the exact dosage regime.

There is an underlying issue of principle as well. Is it good public policy to allow a manufacturer to ‘evergreen’ by changing dosages and making similar ‘inventions’ to keep a product under patent protection indefinitely?

Section 7(i) strikes a balance between the rights of doctors and their patients on the one hand and those of manufacturers on the other. With Israel’s pharmaceutical industry being heavily skewed towards generic manufacture it is certainly preferably politically to refuse a patent like this on grounds of inventive step rather than on patentable subject matter which could be viewed as protectionist.

That said, the issue of patentable subject matter is a ‘hot potato’ that may require updating from time to time, due to TRIPS, world wide developments and as economic issues change. Nevertheless, I think that interpreting claim 1 as not being a method of treatment goes beyond fair interpretation of the Law and as such, the revision should be for the Legislature not for a Commissioner of Patents to decide. That Dr. Noam has chosen to allow Swiss type claims is indicative of Patent Office Policy but should not be sufficient to overcome Section 7(i) which is a clear statement. In this regard however, it is noted that Israel Patent Law is not frequently the subject of Knesset debate, so creative interpretation is probably required to keep practice up to date.  

The applicant is correct that a new dosage of an old treatment is patentable, but I believe this should be true only if the dosage is indeed new. If the dosage existed previously for a different administration regime, the pill is not new. Only the method of treatment is.