Prior Art for Neuroprotective Agents Acting Outside the Blood-Brain Barrier

In asserting "patentable novelty" over a previous patent broadly claiming PBN and its derivatives, United States Patent 5,475,032 (the "Cerovive patent") says:

"The present compound with its two sulfonate groups was expected to exhibit improved water solubility but was also expected to exhibit poor transport across the blood/brain barrier because of its lipophobic character. However, when the present compound was made and tested in vivo, it showed an unexpected increase in efficacy as compared to PBN."

Perhaps this action outside the blood brain barrier was not so "unexpected" after all. E.g, the following prior art paper, uncited:

Neurol Res. 1991 Sep;13(3):160-3.

Prevention of cerebral ischaemic reperfusion injury by intra-arterial administration of superoxide dismutase in the rat.

Roda JM, Carceller F, Pajares R, Diez-Tejedor E.

"...In this sense we have been able to demonstrate that cerebral function , as measured by SEPs, was better in the group of animals treated with intra-arterial administration of an SOD solution. Since SOD has a molecular weight of at least 31,000, the theoretical evidence suggests that cellular penetration would not occur readily nor could the normal blood brain barrier be crossed easily, if at all...."

And there is lots more where this came from. Run this by you local patent attorney.


keywords: nitrone pbn nxy-059 patent

Cerovive is the trademark of the AstraZeneca company.