Canadian Judge: Zyprexa Is An ‘Almost Invention’
10 CommentsBy Ed Silverman // October 23rd, 2009 // 7:34 am
Those who follow the travails of Eli Lilly and its Zyprexa antipsychotic will likely recall that the US patent expires in 2011. This is causing all sorts of problems for the drug maker, because the pill is a huge seller - generating $4.7 billion in sales last year, or 28 percent of overall revenue. This looming expiration contributed to a recent decision to cut $1 billion in expenses and 5,500 jobs.
Meanwhile, an interesting ruling occurred earlier this month in Canada, where a federal judge presided over patent litigation brought by Novopharm, which argued Lilly’s Zyprexa patent - filed in Canada in 1991 and granted in 1998 - was invalid. And Novopharm won. In fact, the Honourable Mr. Justice O’Reilly skewered Lilly’s argument, based on assertions in its patent filings, that Zyprexa was superior to similar compounds developed previously and has a better side-effect profile.
“I cannot conclude from the evidence that (Zyprexa) had substantial and special advantages over the other…compounds,” wrote O’Reilly, who had to decide whether Lilly was entitled to a separate patent for, and a further monopoly on Zyprexa. He later concluded that “I think the best way to characterize (Zyprexa) in 1991 is that it was an ‘almost invention.’”
“It was neither obvious nor a genuine invention. It was a compound that showed promise and, later, some of the early positive indications were borne out,” he wrote (here is the ruling). “Lilly received some early signals of safety and efficacy, but nothing that would support an assertion of surprising and unexpected properties, and nothing that would set (Zyprexa) apart from the other…compounds.”
During an analyst call this week, Lilly ceo John Lechleiter briefly addressed the issue with this terse statement: “We believe this decision is deeply flawed and that it is inconsistent the evidence that was presented at trial and with applicable law. We intend to appeal this decision and protect Lilly’s intellectual property rights regarding the validity of the Zyprexa patent in Canada through April 2011.” Canada is a much smaller market, of course, but the ruling does raise a question about the veracity of Zyprexa as a novel drug.
Nathan
Wow — the first few pages of the ruling you reference make for a fascinating reading for anyone involved in early drug discovery. It show just how important the timing of patent filings is for the creation of value. It turns out that Zyprexa was broadly claimed in by Lilly in an earlier patent that claimed approximately **15 trillion** compounds! A later “selection” patent (in 1991) was filed that specifically claimed Zyprexa as having “special” properties beyond those claimed in the original patent. This is the point under arguement — did they provide enough evidence in the 1991 filing to prove that Zyprexa was truely any different than the other 15 trillion compounds in the earlier filing?
This sort of problem is rapidly going away as Pharma companies become much smarter about how they patent drugs. Typically patents are not filed on such broad groups of compounds anymore and patents are usually not filed till a compound is nearly in the clinic. This maximizes the “exclusivity period” and it minimizes the risk of invalidating your own work (as Lilly may have done). The only drawback is that you open yourself up to being “scooped” by the competition just as you are entering the clinic….
Condor
Maybe Canadian courts will “invent” a new form of intellectual-property: let’s call it “almost novel” and thus, almost patent-worthy.
Then let’s “almost” grant exclusivity — allowing Canadian sales of generic competitors, but only on rainy Tuesdays — and let’s only grant that for “almost” a year — after that, it will be okay to sell generics whenever the Bridge club gathers — but only on folding card tables.
More seriously, while I deplore the endless system of continuing US patents on marginally-novel compounds, especially ones that have now lasted 32 years(!), instead of the intended 17, I think this Canadian Zyprexa one will ultimately be overturned on appeal.
The reasoning here makes for interesting reading, but as many an able judge has said, down here in the lower 48, “hard facts make bad law. . . .”
Namaste
teeth whitening kits
Then let’s “almost” grant exclusivity — allowing Canadian sales of generic competitors, but only on rainy Tuesdays — and let’s only grant that for “almost” a year — after that, it will be okay to sell generics whenever the Bridge club gathers — but only on folding card tables.
SKR
For me the striking/ interesting part was the conclusion.
The Judge almost went to the extent of saying that this selection patent was a [blatant] attempt at ever-greening.
Nathan
This was NOT an attempt at “ever-greening”. It’s an attempt to protect intellectual property that is closely related to prior intellectual property. It comes down to what is “obvious” and what isn’t. Clozapine was developed and marketed in 1975. The clozapine patent “generically” claimed olanzapine (Zyprexa). Note that Zyraxa was never SPECIFICALLY made or described — it was only generically decribed in broad strokes. Clozapine was withdrawn for safety reasons in 1975.
Zyprexa (olanzapine) was patented in 1991. I’ll quote from the below reference: “The prior art references at the time of this invention taught away from using a non-halogenated compound as a substituent in the benzene ring, exactly where olanzapine has a hydrogen atom. When claimed properties differ from the prior art, those differences, if unexpected and significant, may lead to nonobviousness.” (non-obviousness is necessary for “patentability”)
http://www.patenthawk.com/blog/2006/12/generic_anticipation_1.html
This is absolutely not evergreening. This is a case of a company not having a good patent strategy and chemists not being quite creative enough to get away from thier own prior art. Writing patents is truely an art: If you make your claims too narrow, you may get competitors scooping your work. If you make your claims too broad, you risk something like this case.
Daniel Haszard
Eli Lilly has made $38 billion on Zyprexa and it was way oversold and caused diabetes and in some cases sudden death.
Eli Lilly has received a huge criminal fine over their Zyprexa cash cow,add it all up comes to $4.6 billion, in Zyprexa settlements,fines,litigation.
Addictive Zyprexa was pushed by Lilly Drug Reps.
They called it the “Five at Five” (5 mg at 5 pm to keep nursing home patients subdued and sleepy) and “VIVA ZYPREXA” (Zyprexa for everybody) campaigns to off label market Eli Lilly Zyprexa as a fix for unapproved usage.
Eli Lilly is ‘reaping the whirlwind’ for aggressive marketing of Zyprexa that has caused suffering and deaths.
There must be millions out there harmed by this drug.
Daniel Haszard http://www.zyprexa-victims.com
Brother
Just clarifying Nathan’s comment, clozapine was withdrawn in 1975 but brought back in 1989 with five black boxes. It could never have been marketed as Zyprexa was.
Nevertheless, despite compliance with all pt. instructions, the drug killed my sister in 2000.
foln16
Nathan writes that the solution to Lilly’s problem here would be to wait until the “new” compound is ready to go, presumably so more is known about it and the applicant can demonstrate the special characteristics of the compound in the selection patent relative to class of compounds in the genus patent. This seems to be supported by the ruling here as well, since the overarching criticism of the judge in this case was that Lilly’s scientists did not know (and therefore did not disclose) the special characteristics of olanzapine at the time of the selection patent application in 1991: “the evidence just was not there, yet” (p. 58, para 154). But doesn’t this line of reasoning cause other problems, in terms of losing novelty?
Condor
Yes, it does, foln16 –
It also (quite probably) would have meant that the original patent would have expired prior to grant of the now-contested one. . . .
Thus — while it may be that no “gamesmanship” was actually attempted here — it is also quite likely that had the patent lawyers waited until these special properties were clearly known, the exclusivity for the original filing would have lapsed, anyway. Game over.
So, perhaps it is “six of one — half dozen of the other” — now that a Canadian judge has leaned toward tossing it, anyway.
Namaste
Nathan
Good point Condor - I hadn’t looked at it that way.
Chemists have really boxed themselves into corners over the years by filing patents on such broad classes of compounds. Now we’re stuck with the mess we’ve created.