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Kinase Chemistry – Just a year and a half behind the times.

Don’t abuse inventorship: Scientist

Posted by kinasepro on August 16, 2007

So a guy named Brian Druker wrote this piece on how Gleevec is overpriced, eh? Who is he? Well he appears to have written his own byline in case you hadn’t heard:

THE?

A quick googlification suggests he has plenty of nice things to say about Brian Druker and his role in Gleevec’s discovery… To his credit he does list Jürg Zimmermann (the named inventor on a series of patents starting with EP564409) as one of the ‘unsung heroes‘ in a history of Gleevec essay.

According to Zimmermann the discovery went something like this:

etc.

ht: spicy ip, via pharmalot

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13 Responses to “Don’t abuse inventorship: Scientist”

  1. milkshake said

    The interview with Zimmermann is a very good read – the guy does not seem phony or pompous and does not put up some self-important baloney.

    As you know every success has many fathers but a failure is an orphan. For example if you were, as a computer modeler, involved in SAR discussions in a project that eventually resulted in a succesfull drug – but you did no bench work by yourself – would you later claim to be the key co-inventor of the drug? Some people woul do this without hesitation.

  2. What’s wrong in being a key co-inventor if you have actually floated the idea?? Key inventor is a different matter. There can be many key co-inventors.

  3. TMS said

    I have always wondered about that discovery graphic. Novartis was one of the “life science” companies that was put together in the 90’s.(Agricultural and Pharmaceutical research synergies were expected from them) They had a 2-anilinopyrimidine agricultural fungicide named cyprodinil coming out on the market in the years before the Gleevec discovery story began. There had to be hundreds of 2-anilinopyrimidines in their compound files at that point. From what I have read they say it was designed from the very beginning, but sometimes it helps to have the right compounds in the vials in the company compound libraries.

  4. kinasepro said

    I agree with Milshake, if any of you haven’t read the Zimmermann piece: do so.

    And on modelling and anilinopyrimidines… One provacative idea is that if they had a crystal structure of the first anilino-pyrimidine above bound to PKC, that they may never have made a compound like gleevec! From a structural perspective the xray may have suggested a pazopanib-like binding mode.

  5. One of the problems also is that X-ray crystallographers sometimes don’t fit the ligand to the density too well. And there are some things, like amide flips and polar states, which are ambiguous even when the density is good. Proteins, they usually do a great job of fitting, but ligands are another matter. One of the reasons simply is that often, crystallographers are not as concerned about ligands as they are about proteins (when ligands are co-crystallised)
    Friesner et al. have developed one protocol for assigning correct polar states and amide flips. See for example:
    PROTEINS: Structure, Function, and Bioinformatics 66:824–837 (2007)

  6. OrgMed said

    Composition of matter is the critical for chemical patents, many patents these days with generic claim structures which are not synthesized in the lab are still in chemical patent. The inventors who designed using computational tools, SAR or MedChem based can be a key inventors. Medicinal chemists think that they physically made the compounds in the lab feels that they are the key inventor even though some one asked them to synthesize the compounds. In the case of biologists, once they test it and found active they feel they are at fisrt in the discovery graphics (Drukar ???). If no activity, they come of with several questions without understanding the real mechanism of action that why these are inactive. I think prior to the synthesis any knowledge on chemical structure are the ones key inventors later the person who synthesized.
    Dr.Jurg is definetly a great medchem who directed the group with ideas
    if not he wet his hands in making the STI-571.

  7. kinasepro said

    inventorship

    Interestingly, in the US its about ‘Intellectual Domination’.

  8. milkshake said

    I was talking about claims of being the *key* co-inventor, about the honesty and modesty in a team effort.

    The ideas are quite cheap and plentiful, trying them out is the hard part. – I can have a quick glance on your structure on the monitor and I will give you ten good ideas what you should be making. (It will make you busy for next three months to try them out and the next week I will give you another ten ideas and so on. The process is particularly facile for the modeler who has no clue about how the synthetic chemistry actually done).

  9. It depends on exactly *what* the modeler is suggesting. Some ideas can be cheaply discovered, others may not be, and in any case, modeling does give those ideas in the first place. It could be a question of rigid docking and then looking for extensions in the molecule, but even in that case, one needs to have good knowledge of the docking algorithm, and the capacity to distinguish good poses from bad ones, as well as evaluate all the poses, possibly doing some post-docking work. In some cases, there may be induced fit mechanisms that can be gleaned from MD simulations, thereby suggesting other structures. Or one may need to do QM-polarized docking to get better poses. If synthetic chemists are aware of all of this, they are more than welcome to do it and then make the compounds themselves. The question is not if they can do it, but if they do. If a modeler suggests a compound and the synthetic chemist did not come up with its structure, the modeler *is* a key player along with the chemist who made it. That surely is not taking away credit from the synthetic chemist, and does not undermine his/her importance. The point is that this should always be a process of synergy. In any case, it is always a lively and controversial issue to decide who are the key players, but I wholly agree that every effort should be made to apportion credit fairly.

  10. OrgMed said

    Seems like its hot topic to discuss witin the multidisplinary drug discovery process. Ideas may be cheap and some time very meaning full (In kinase field definetly you can take a look at the scaffold/chemotype and get plenty of cheap ideas). If synthetic chemist know quite a bit of Medicinal chemistry he can build nice SAR and optimize the leads. If the medicinal chemist has experties in computational work and synthesis (quite a few are there in pharma industries) and then all the problems are taken care on the inventorship. Give importance to Med/Comp/Synth associates, because everybody is doing the work, not only the person who is standing at the hood doing the work Dr.milkshake.

  11. milkshake said

    I never claimed to be a Dr. or an expert in molecular modeling. When writing the first comment, I had some person(s) and project(s) in mind, the situations where I know excatly what contributions of participants were, and how it was later re-interpreted.

    To which I could only add that when a perceived huge personal financial gain is at stake, the honesty gets ditched faster than you can say “venture capitalist”:.

  12. susiejo said

    Gleevec was developed at MD Anderson by a molecular biologist and small team. Brien Drucker was a clinician who was bought on the project to run drug studies after the drug was already designed (i.e. he did not design imatinib though he often seems to leave that impression). The molecular biologist who did was let go on short notice after the first trial and got shit for his work – take the hint if you think there is money to be had by designing a drug of that caliber.

  13. kynase said

    it originated from cellular screening using BCR-PDGFRb, a fusion protein similar to BCR-Abl, expressed in IL3-dependent mouse myeloid cell line. In a discovery process, floating ideas of thousands of compounds every week is easy, making a few of those is more difficult, and knowing what these few do is harder even. managing the process, making it visible and following-through are top-of-the-art in the business. its CML project leader should take most of the credit.

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