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Comment by randomacct3847 | Hacker News Reader

Actually I just read that Esketamine is patented while Ketamine is not, even though it’s essentially the same thing. So JNJ can charge these ridiculous prices because they changed one small thing about the drug so they could slapped a patent on it.

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Welcome to pharmaceuticals in general (and many of the biggest biotech companies, come to think of it). I didn't find the exact number in a cursory search, but I've read that a fairly preposterous proportion of the drugs that have ever been produced are (unpatentable) plant molecules that were deliberately reverse-engineered and tweaked for patentability.

It’s a sad joke. If the gov’t wants to fix drug prices then figure out how to stop companies from gaming the system like this.

It could either bring drugs to market itself, negotiate for all consumers (single payer), or loosen FDA regulations around drug safety or efficacy trials. The status quo is that selling a drug is extremely expensive even when if you know a priori it is safe and effective, so companies must use the patent to seek high rents to recoup their costs (as well as cover R&D on other drugs, which may not pan out).

Yet prices are sufficiently high that it is a surprisingly profitable industry. It is also worth bearing in mind that the government find a large share of drug development. [1]

[1] "pharmaceutical and biotechnology sales revenue increased from $534 billion to $775 billion between 2006 and 2015.... Drug industry spending for research and development increased from $82 billion in 2008 to $89 billion in 2014" (I assume there are other costs so one cannot simply divide to get gross profit but it seems illustrative)

https://www.gao.gov/mobile/products/GAO-18-40

The pharmaceutical industry inflates costs of drug development.

https://www.nytimes.com/2014/11/19/upshot/calculating-the-re...

The costs may be inflated but the actual costs are probably not that different than tufts. Several other studies suggest pharma is getting a return on its r&d investment of under 5% (a Deloitte and McKinsey study as well as a Novartis one). Pharma is also cutting internal r&d because they can't get a return. They buy drugs from startups instead which does not show up in the profit and loss statements

In 2018 only like 12% of new FDA approved drugs were developed by big pharma. 63% were developed by small companies. A negligible amount / zero were developed by universities

The $161M figure cited in that nytimes study is not at all representative because most early stage r&d is done outside of big pharma, and then big pharma buys the drugs and markets them

If drug research was profitable pharma would be doing more of it, not less

Analyses like that are misleading because most of the industry's revenues and profits are concentrated with a few firms. The vast majority of biotech and pharma companies are not profitable and never aim to become profitable -- rather they just do r&d and then sell drugs to big pharma once some of the clinical risk is taken out

In 2018 only like 12% of new FDA approved drugs were developed by big pharma. 63% were developed by small companies. A negligible amount were discovered by universities alone

Pharma acquired these drugs from startups through M&A which doesn't show up in profit and loss statements. It shows up on the balance sheet

That $84B r&d figure seems very low. The top 15 pharma companies spend something like $75B a year in r&d. VC backed startups spend like $10-15B. Then all the firms in between account for the majority of spending. Don't remember the source but I think total global pharma r&d is like $200B

I'd be interested in seeing data on that, as I have never heard that argument

A cursory look at the top selling drugs of all time doesn't appear to show any plant derived drugs [0]. Obviously this does not disprove your statement but its the quickest heuristic i could think of

[0] https://en.wikipedia.org/wiki/List_of_largest_selling_pharma...

That list is sorted by price; i.e., it will bias towards recent patents on complicated drugs.

OP's statement was about sheer number of patented drugs. I don't know that OP's statement was accurate, but the wikipedia link doesn't really refute or confirm the idea.

The list of drugs that have been derived from plant sources is actually quite low.

And just because it’s present in a plant doesn’t mean it can be drugged. It could have a short half life, high toxicity, etc., so derivatives are made to optimize it’s action.

Finally, even if a patent can’t be secured, the first version of a drug is given exclusivity by the FDA - they won’t approve another version up to 7 years (orphan drugs).

"Esketamine" is just the S-isomer of ketamine (thus "S-ketamine"), which has conventionally been an equal ("racemic") mixture of the S- and R-isomers. It's not so much that they've changed anything about the drug as that they've isolated the variant which is more psychoactive.

Ok - but just isolating the active part of the drug makes it patentable. Still ridiculous given how cheap Ketamine is.

It is completely ridiculous. S-ketamine has been available on the black market for years - it's not like anything about this is rocket science.

If that's true, maybe their patent is invalid.

But maybe there's also a patent on the delivery mechansim. Or maybe it's a process patent.

Sure; we know they have a valid patent or else it would not have been worth their time to bring the drug to market.

Seriously?

Janssen obviously believes that it's valid. Or at least, they're confident that they can defend it. Maybe they know that it's not valid, but are confident that others won't figure out why.

In one case that I recall, the manufacturer bribed a chemist to retract a paper that had reported the synthesis of their drug.

Many years of budget cuts have rendered the Patent Office pretty clueless about drugs. And the FDA doesn't do any independent assessment of patent validity. I've seen testimony where FDA staff said that they lack expertise for that.

So basically, patents are valid if they survive litigation.

It's not just budget cuts. It's an exploding legal system behind patents. Try to decipher the patent rules [1] sometime. It's filled with incredibly counter-intuitive self referential legalese that, even when one understand the jargon, is not entirely clear. And it regularly has very major changes made to the entire code. In general as you approach some degree of complexity in anything, the number of individuals who sufficiently grasp it approaches 0. And then as you're mentioning - that's only about the patent legalese itself. Now the patent examiners also need to be able to have an understanding of what are ideally novel new inventions in various fields, which themselves are often increasingly obfuscated.

Anybody could perform a sufficiently capable of job this has way better career opportunities than earning $80k at the patent office. While this does support your notion of budgetary cuts being the primary problem, again I think that misses the core problem which is that the system has become so convoluted that actually having a meaningful holistic understanding requires immense skill and education. Systems that are supposed to be for public, and individual, use should not require a juris doctor to begin to parse.

The whole system needs a major overhaul, frankly like much of our formal structures. Isn't it a bizarre system that people are expected to completely obey laws which they are in no way expected to be able to completely understand?

[1] - https://www.uspto.gov/web/offices/pac/mpep/index.html

It's valid because USPTO approved it, yes. We're first-to-file, not first-to-invent now.

True. But there's still the on-sale bar:

> "A person shall be entitled to a patent unless . . . the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention."[0]

0) https://www.whitecase.com/publications/alert/supreme-court-s...

Right. And unless the inactive R-isomer has some negative effect, it's a meaningless change.

Ketamine isomer (S+) induces less drowsiness, less lethargy and less impairment in clustered subjective cognitive capacity than equianalgesic small-dose racemic ketamine. In addition, S(+) ketamine causes less decline in concentration capacity and primary memory [Pfenninger et al. 2002]. The S(+) isomer of ketamine has about twice the analgesic potency of the clinically used racemic mixture. Therefore, the known side effects may be reduced when one half of the usual dose is administered.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910398/

Thanks.

But if S(+) ketamine has been commercially available, even if only illegally, it's not patentable.

Not quite, the specific purification process may or may not be patentable.

True. Process patent. But those are harder to defend in litigation, as I recall.

R isomer is quite active too and similarly, which is why nobody bothered with purified S isomer.

They ran 35 clinical trials to get FDA approval.[1]

How could they recoup those costs without IP protection?

[1] https://clinicaltrials.gov/ct2/results?cond=&term=Esketamine...

Any psychiatrist can likely prescribe ketamine off label for use at home if they choose. Mine does.

Thanks.

So the next version will be monetizing the delivery system.

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