Renovis Patent Problems, One example

"That which will infringe, if later, will anticipate, if earlier." Knapp v. Morss, 150 U.S. 221, 14 S.Ct. 81, 37 L.Ed. 1059 (1893).*


Among other bars, patent law precludes patenting anything published more than a year before the relevant application. The law also requires the applicant to reveal such "material prior art" to the examiner.

If inadvertently omitted, such prior art only invalidates relevant claims. However, willful failure to inform the patent examiner of it constitutes "inequitable conduct" and invalidates the entire patent. My patents aside, weak patent protection will likely result in an "Abbreviated New Drug Application" (ANDA) against AstraZeneca to market a generic form of Cerovive.

Just one example: the following report of therapeutic use of PBN was published after my priority date. So it is clearly not "prior art" to me. But, it was published more than a year before Centaur's ( now Renovis' ) first application in 1989.


Free Radic Res Commun. 1986;1(5):321-7.

"Phenyl-T-butyl-nitrone is active against traumatic shock in rats."

Novelli GP, Angiolini P, Tani R, Consales G, Bordi L.

Institute of Anesthesiology and Intensive Care, Policlinico Careggi, University of Florence, Italy.

Abstract
"Oxygen free-radicals appear to be involved in the pathogenesis of shock; therefore trapping of these radicals would modify the evolution of experimental shock. Experiments were performed on rats submitted to 100% lethal whole body trauma (rotating drum) and their survival, pathology, acid-base status and hematocrit level observed. The spin trapping agent phenyl-t-butyl-nitrone (PBN) was administered before trauma (50, 100, 150 mg/kg i.p.) or at various intervals (30, 60 minutes) after establishment of a severe traumatic shock. It appeared that PBN administration was highly effective both in prevention and in reversion of traumatic shock in rats."


Compare this to a typical Centaur ( and now Renovis ) patent:

United States Patent RE35,112 Carney , et al. December 5, 1995

Phenyl butyl nitrone compositions and methods for treatment of oxidative tissue damage

Citing other Novelli papers to the same effect without comment, this patent incorrectly states:

"In summary, while PBN has been used in a number of research studies, there has been no data to support the proposition that it could be useful in vivo,...."


Similarly, while citing the Novelli paper ( i.e., they knew about it ), US Patent 5,681,845 ( Janzen, et al. October 28, 1997, DMPO spin trapping compositions and methods of use thereof ) states:

"Phenyl butyl nitrone (PBN) has been used in a number of these in vitro research studies using spin trapping to look for free radicals, but until demonstrated by the data in U.S. Ser. No. 07/422,651, (filed Oct. 17, 1989, now U.S. Pat. No. 5,025,032) there has been no data to support the proposition that it can be useful in vivo, particularly with respect to treatment of tissue damage in the central nervous system."

Note that this patent does not directly involve PBN or its derivatives per se.


US Patent 5,622,994 Carney ,et al. April 22, 1997 Spin trapping pharmaceutical compositions and methods for use thereof

" Phenyl butyl nitrone (PBN) has been used in a number of these in vitro research studies using spin trapping to look for free radicals, but until demonstrated by the data in U.S. Ser. No. 07/422,651, (U.S. Pat. No. 5,025,032) there has been no data to support the proposition that it could be useful in vivo...."


The following seem to be the primary patents for "Cerovive"

U S Patent 5,488,145 Carney January 30, 1996, "2,4-disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceutical free radical traps "

U S Patent 5,475,032 Carney December 12, 1995 2,4-disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceuticals

United States Patent 5,508,305 Carney April 16, 1996 2, 4-disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceuticals

Among other problems, none of these patents tells the examiner about Novelli, above, only noting without citation:

"In the mid 1980s, the first possible therapeutic effects of PBN were implied when severe trauma ischemia animal tests showed that PBN-treated animals were more likely to survive than controls."

To what does this ambiguous passage refer ? These patents do cite earlier Centaur patents 5,036097 and 5,025,032. Possibly, the examiner believed that this passage referred to these. The subsequent patent below repeats the "but until...there has been no data..." error.


US Patent 6,002,001 Carney , et al. December 14, 1999 Spin trapping pharmaceutical compositions and methods for use thereof

" Phenyl butyl nitrone (PBN) has been used in a number of these in vitro research studies using spin trapping to look for free radicals, but until demonstrated by the data in U.S. Ser. No. 07/422,651, now U.S. Pat. No. 5,025,032 there has been no data to support the proposition that it could be useful in vivo, particularly with respect to treatment of tissue damage in the central nervous system. "

However in this 2002 review article Centaur's researchers do report the Novelli paper.


www.nitrone.com

Speaking of intellectual property: Cerovive is the AstraZeneca company's registered trademark for PBN disulfate or nxy059.



* "Knapp" has some interesting effects. E.g., a suit claiming "infringment" when the alleged infringing use (say, an ANDA) is based upon a prior-art patent essentially admits that this patent "anticipates".