
Computer program that could bypass patents to produce synthetic drugs - zhamisen
https://www.europeanpharmaceuticalreview.com/news/83106/intellectual-property-patent/
======
jordigh
> In the global industry, some of the best kept secrets are those necessary to
> make life-saving medication and other pharmaceutical products.

What? Patents are not secret. Patents are the opposite of secret. The very
word "patent" means "open". Are drug patents some kind of trick to do the
opposite of what a patent is supposed to do?

> However, when the researchers designated some atoms and bond as untouchable,
> the program proposed plans that avoided the patented ones.

Can someone explain just exactly how do drug patents work? Can this legally
work? I understand that normally patents cover processes or working
inventions. I didn't think that the precise chemical bonds were required to be
produced in the final output of a patent.

Also, since apparently the researchers have read the patents in question and
designed their software to produce drugs that avoid those patents, have they
willfully infringed? Since they were aware of the patent and the process by
which the drug worked, so using this knowledge they produced similar drugs
that do the same thing?

I assume that the researchers know drug patent law well enough and are
confident that their method avoids patents, so there's obviously a lot I don't
understand.

~~~
adamzk
I'm a patent holder for a pharmaceutically relevant class of compounds. There
are two types of patents typically seen in pharma. One is procedural (how the
drug is synthesized, isolated, formulated or administered) and another is
composition of matter (the atoms in the molecule, their relative coordinates
and the lengths and types of bonds that connect them). This program takes a
target compound and does two things. 1) produces a library of similar
compounds by structural diversification (making substitutions of atoms or
small groups of atoms in the target compound with other atoms or groups which
are known to behave similarly) with restrictions based on what has been
patented under composition of matter. 2) It then takes each molecule and looks
for ways it can be synthesized. It does this by breaking apart the molecule
piece by piece until it obtains commercially available building blocks. These
piecewise separations correspond to synthetic a steps in the other direction,
which the program screens for literature precedence. It does this for every
possible combination of piecewise separations until it finds a set of viable
pathways from available compounds to the target. This is called retro
synthesis. It then filters the potential synthetic routes for those that are
covered by procedural patents until it has a list of non patented,
commercially viable synthesis plans.

As you can imagine there are thousands of ways a moderately complex molecule
could be deconstructed and the bank of known reactions is more than any one
person can really grasp. That and the myriad patent literature and how cryptic
and dense it can be make the problem particularly suited for algorithmic
treatment. This is only being done now because cataloging all the research and
patent literature (which goes back to the late 1800s) and digitally formatting
in a way that allows it to be computationally analyzed and processed requires
manual translation of each report by a human being. Not many people have the
expertise required for this and those that do usually prefer less menial work.
So it has taken this long to amass a digital library of sufficient size to
give one confidence that the answers it provides are comprehensive and that
further searching would be pointless.

~~~
yholio
> The research team hope that their software could help pharmaceutical
> companies in the protection of their intellectual property, and to hasten
> research into organic chemistry.

It seems what they are attempting to sell is a IP protection service: let us
show you other molecules and synesis routes you should also patent
defensively, without actually attempting them in practice. Pretty soon you
will have algorithmically defined patents.

It's IP anti-science at it's worst.

~~~
anilakar
A not-so-fun fact: My country used to be on the 301 Special Report (IPR "rogue
country" list) until 2015 because American pharmaceutical companies didn't
consider procedural patents good enough. The last patents in that category
were issued in 1995...

Apparently the income of Big Pharma investors is more important than the
affordability of generics.

~~~
michaelcampbell
> Apparently the income of Big Pharma investors is more important than the
> affordability of generics.

You say this as if it is surprising.

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sachindhar
Lots of misinformation in these comments. Both the process and end product are
patentable, but some companies do not disclose their processes and opt to keep
them as trade secrets.

As for the article, changing the molecule can have unpredictable effects on
how the compound acts in the body. Even changing one bond/atom can result in
dramatically different properties. The article doesn't address that.

~~~
sbierwagen
More relevantly, this scheme doesn't address the _prescription_ side at all.

Doctor: I judge you to have [medical condition]. Here is a prescription for
[expensive on-patent drug].

Patient: I would prefer to take this less expensive drug, which a computer
program thinks might be equivalent.

Doctor: Hmm. Doesn't look like there are any clinical studies for this
analogue drug. Since I don't want to risk a malpractice lawsuit, I'm not going
to prescribe it. Without a prescription, your insurance won't pay for the
analogue drug either, so it'll have to be cheaper than your copay in order for
it to make sense for you.

~~~
riahi
The conversation goes more like this:

DOCTOR: You have [medical condition]. We can manage it with [medication which
is on the appropriate tiered formulary for the patient’s pharmacy benefits
manager].

PATIENT: I would prefer to take this medication they advertised to me during
the last football game.

DOCTOR: This medication is only a slight incremental improvement over the
generic one approved by your insurance. If you want the newer one, it may have
higher copays and will have more paperwork hassle as we try to get the
insurance to cover it. In the end, it may not be covered. Do you still want
it?

PATIENT: Yes. [Leaves angry Yelp review over how the physician wouldn’t
prescribe them X medication].

END SCENE

As for the final point, if there are no clinical studies (at all) for a given
drug, then it is not FDA approved and would be illegal to prescribe unless
under the auspices of a registered clinical trial with a filed IND with the
FDA.

If it is FDA approved but not for that specific indication, then it depends on
the clinical practice patterns at large whether this is a reasonable course of
action vs malpractice. Case in point: Avastin is way cheaper than Lucentis for
macular degeneration and works via similar mechanism, but was never tested or
approved for that indication. Many Retinologists will inject Avastin anyway
because some trials have shown benefit for cost conscious patients or patients
from whom insurance will not cover Lucentis. This is not malpractice.

Using another drug from another class entirely without any clinical evidence
to back up its use outside of a trial could be considered malpractice, but
only provable if there is a bad outcome.

Without a prescription, they aren’t getting the drug legally. With a
prescription without insurance/PBM approval, then yes, it could be very
expensive for unconventional treatments.

------
zhamisen
Link to the paper:
[https://www.cell.com/chem/fulltext/S2451-9294(18)30567-9](https://www.cell.com/chem/fulltext/S2451-9294\(18\)30567-9)

------
fernly
But isn't a modified molecule a reformulation, which cannot be assumed to have
the same effect, or dose-response, or even safety, as the original molecule?
Say if you can synthesize something _like_ garblezolib or whatever, aren't you
then faced with all the safety and effectiveness trials that were so expensive
for the OEMs?

~~~
jamiek88
The end molecule is not patented, the process and pathway to creating it is.

If this software can come up with sufficiently novel pathways other processes
can be used to come up with the same drug.

This is the idea anyway.

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234dfgdgdf
It could bypass patents, but instead it is owned by Merck, Giant Pharma so
they can now bypass all the patents for themselves

~~~
refurb
Exactly! I’m sure the first customers of this software will be the big pharma
patent departments who will use it to further expand their patent space.

------
bentona
I love it when sci fi and sci fact seem to merge
[https://www.npr.org/2017/09/20/548664924/in-a-future-
ruled-b...](https://www.npr.org/2017/09/20/548664924/in-a-future-ruled-by-big-
pharma-a-robot-tentatively-explores-freedom-and-sex-aut)

------
User23
More on this:
[https://blogs.sciencemag.org/pipeline/archives/2019/01/18/au...](https://blogs.sciencemag.org/pipeline/archives/2019/01/18/automated-
route-finding-and-patent-busting)

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leoh
This article is not complete. In order for a drug to be approved by the FDA
for a particular condition, it must demonstrate (through expensive clinical
trials) superior efficacy to existing treatments unless the drug is considered
a generic. It's hard to say if a drug with slight molecular modifications
could be said to be a "generic" form of another. There's a good chance the
answer would be no, because slight molecular modifications can cause
significant differences in efficacy.

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monochromatic
Some commentary from my favorite chem-blogger:
[https://blogs.sciencemag.org/pipeline/archives/2019/01/18/au...](https://blogs.sciencemag.org/pipeline/archives/2019/01/18/automated-
route-finding-and-patent-busting)

Sounds like this is for finding different synthetic routes to the same
molecule. So it might help avoid method claims, but not claims for the product
itself.

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laughingman2
Information wants to be free.

