Federal Circuit Affirms Nonobviousness of Plavix Isomer Patent

Sanofi Synthelabo v. Apotex (Fed. Cir. 2008)

In an opinion by Judge Newman, the Federal Circuit affirmed the validity of Sanofi’s patent covering the blockbuster drug Plavix. The Plavix patent covers a dextrorotatory isomer. The validity question rises from the fact that the racemate of the compound was known and described in earlier Sanofi patents. For its obviousness argument, Apotex noted that separation of enantiomers is routine and that there are many examples of compounds that exhibit stereoselectivity. Thus – Apotex argued – there was both motivation and means for creating the Plavix compound from the known racemate that Sanofi had previously admitted was an important compound.

The Federal Circuit disagreed with Apotex – finding “no error in the district court’s findings that, on the state of the prior art, a person of ordinary skill would not have had the expectation that separating the enantiomers would be likely to produce an isomer having absolute stereoselectivity as to both the favorable antiplatelet activity and the unfavorable neurotoxicity.”

Notes

  • This case falls in line with the Federal Circuit’s 2006 decision on preliminary injunction in this case. [Link]
  • In November 2008, the Canadian Supreme Court affirmed patentability of the Canadian patent on Plavix. [Link]

99 thoughts on “Federal Circuit Affirms Nonobviousness of Plavix Isomer Patent

  1. 99

    EXACTLY this question recently occupied the British Supreme Court, Nice, so answers to your question are eagerly awaited, at least by this particular reader. Many people find Lord Hoffmann’s decisions particularly refreshing. I’m guessing that Pauline Newman is amongst them.

  2. 98

    BioCase–

    I consider myself someone who “actually understands chemistry” and I agree that, sometimes, applying routine purification is hard. I have encountered some difficult purifications in my day and crystalizations (as this particular chiral resolution was) can be the most frustrating. In these cases, trying different solvent systems can be tedious and time consuming– but this does not make the “idea” to crystallize a target compound somehow innovative.

    Would you agree that, in Sanofi, the innovation and accomplishment came in discovering the conditions for resolving the particular enantiomer and not in forming the idea to separate the enantiomers?

    If so, shouldn’t we award patent protection on the technique for isolating the enantiomer? Then, only the actual innovation would be protected. And, if the technique were really innovative, this protection would ensure commensurate rewards via its exclusive use.

    Extending the reward to the enantiomer compound itself (Papesch) seems to reward the technician (who resolved the enantiomer) for the efforts of the inventor who created the racemic compound. As a result, new ways to purify a compound take away from the more important invention– discovering the compound. Wouldn’t this actually lessen incentives to create new drugs because one could maximize profits (with less investment) by waiting for someone else to discover a drug, then piggy backing off of those efforts by, e.g., resolving a racemate?

  3. 97

    Those who actually understand chemistry will appreciate the soundness of this decision. This court has been brutal to pharmaceutical patents for the past several years and it’s good to see somewhat of a turning around in ’08. Here, the court correctly found that that the enantiomer was prima facie obvious in view of the prior art racemate. It also properly found that the mere fact that the art discussed preparation of enantiomers and their salts was not an “anticipation” of those enantiomer salts but rather simply rendered them prima facie obvious. This court has not always displayed such clarity on this issue and it’s a welcome reprieve

    The academics in the blogs, who know not chemistry nor ever wrote a claim in their life sit in their ivory towers and complain about this case. The reality is however that this was a very difficult enantiomer to prepare. Most significantly, Sanofi showed that enantiomers with higher activity also have attendant higher toxicity and the court gave proper credence to testimony in this regard.

    Well done by this court. It’s nice to see that there are at least some patents that will be upheld and US jobs preserved.

  4. 96

    Interesting that Papesch dates from 1963. I think the Germans switched to their absolut Stoffschutz in 1967, following the CCPA, I shouldn’t wonder (after all, they follow the USA on DoE). What goes around comes around, and there have been plenty of murmurings, in recent years, about the success of petitioners for IPR over the last 40 years, in pushing the envelope of what’s patentable, and how much scope of protection they should be awarded. Society has a duty to push back, but should be careful not to over-react. We still need new drugs, but should the Supremes look again at Papesch, perhaps?

  5. 95

    3d-

    You cut right to the center of what I consider the problem. The Patent System (as articulated in Art. I, section 8 of the Constitution) is supposed to reward the discoveries. If the isolation is somehow inventive, a “method of purifying” claim seems appropriate; if the treatment was made possible by the formulation/enantiomer then a “method of treatment” claim seems appropriate. To me, Papesch really opened a can of worms by saying that a compound and all of its properties are one in the same thing. This allows anything RELATED to the compound to serve as a means for patenting a compound.

    Thanks for your response- you’ve really sharpened the point.

    Have a great weekend everyone.

  6. 94

    “All of the noise in the opinion about the chemist’s struggle really just told the story of a poor technician.”

    NiceLlama’s comment is exactly why I take issue with the result in this case – as someone who has isolated many enantiomers as a technician, I can tell you it’s pure “sweat of the brow” (read: boredom), not ingenuity. And the fact that they were not patenting it narrowly (as “Cure for disease Y, being enantiomer X_left”) means they did not deserve the patent on all uses of that enatiomer, including the obvious ones. At best, they should receive a separate use patent. As some blogger likes to comment (I think it’s on Broken Symmetry), it was Adam Smith who started all of this – we’d protect the sweat of the brow laborer if he was also the inventor. Hence protecting inventors for their inventive work, not protecting corps’ monopoly on isomers they would isolate anyway, as part of their normal course of business (and then hire an expensive lawyer to explain how innovative and taught-away-from it was).

    Now that I’ve ranted: What am I missing here?

    And re: “recommended reading: link to stthomas.edu

    …Thanks, reading! That was a very good piece (if a wee bit sappy). The idea that we should take off the zealous advocate hat when interacting with each other is solid. This article could help save many lawyers’ jobs, marriages, blood pressure levels… As a new reader, I must comment that everything is much more interesting and thought-provoking when you all stop cr*pp1ng on each other.

    Finally, Max, I would love if we returned to Germany’s method of 40 years ago, from what you write. If the incentive to research would be lost if we stopped allowing patents on things that are easily found using the current state of technology, then I think we are all very lazy. It’s as if I deserve a patent on the list of sites that I googled today, because it took me a long time. Not to say this is what is happening generally – I share the concern of many about the decline in granted patents and what it might mean for the future of American innovation (though, at present, we have no indication what it means.)

    OK, I’ve killed three hours on this site, so I thought I could kill five minutes of your time with these thoughts. Thank you, Dennis, for this blog. Best to all of you.

  7. 93

    Nice comments, Llama, which I take as vindication of the line of thought I offered above, namely that “Enantiomer X_left” ought to be obvious but “Cure for disease Y, being enantiomer X_left” might not be, depending how unexpected is the performance enhancement of the enantiomer over the recemate. But, as Paul Cole explained, that’s not the way the courts have seen it, these past 40 years.

    Before then, Germany did block claims giving absolute protection to molecules. My point is that the EPO’s problem and solution approach to obviousness would fly better, in the chemical arts, if it went back to doing what Germany did 40 years ago. But you and others will tell me that big pharma would certainly then get very upset, and would complain about the incentive to research being lost. Actually, it wouldn’t be, would it?

  8. 92

    Max:

    “When you write ‘It’s easy to lift yourself off the ground. Just use the conventional wing-flapping method’ that doesn’t enable flying.”

    I agree- this would not enable flying. However, the Sanofi case is more akin to “It’s easy to lift yourself off the ground, just use conventional air travel (e.g., airplane, helicopter, balloon, etc.)” Resolving one enantiomer from a mixture can be accomplished quite easily. While “conventional air travel” would require you to search for a flight and drive to the airport, I am confident that your lifting yourself into the air would be enabled.

    All of the noise in the opinion about the chemist’s struggle really just told the story of a poor technician. I think almost all enantiomers can be isolated on the small scale by using a chiral column– this could be done the same day the racemic mixture was made. Larger scale techniques like crystalization would take a little while to optimize- I have observed this process taking an undergraduate a couple of weeks but she did have a full class load keeping her busy.

    If a small quantity of the enantiomer is immediately available upon synthesizing a racemic mixture shouldn’t that enantiomer be inherently anticipated or at the very least obvious. Or do we need to wait for a technician to perfect an economically beneficial technique?

  9. 91

    Max:

    “When you write ‘It’s easy to lift yourself off the ground. Just use the conventional wing-flapping method’ that doesn’t enable flying.”

    I agree- this would not enable flying. However, the Sanofi case is more akin to “It’s easy to lift yourself off the ground, just use conventional air travel (e.g., airplane, helicopter, balloon, etc.)” Resolving one enantiomer from a mixture can be accomplished quite easily. While “conventional air travel” would require you to search for a flight and drive to the airport, I am confident that your lifting yourself into the air would be enabled.

    All of the noise in the opinion about the chemist’s struggle really just told the story of a poor technician. I think almost all enantiomers can be isolated on the small scale by using a chiral column– this could be done the same day the racemic mixture was made. Larger scale techniques like crystalization would take a little while to optimize- I have observed this process taking an undergraduate a couple of weeks but she did have a full class load keeping her busy.

    If a small quantity of the enantiomer is immediately available upon synthesizing a racemic mixture shouldn’t that enantiomer be inherently anticipated or at the very least obvious. Or do we need to wait for a technician to perfect an economically beneficial technique?

  10. 90

    1. The drug was known in its racemic form.

    2. Isolating an enantiomer from a racemic mixture comprising it is certainly obvious, especially here where high doses of the racemate caused problems– My old boss required me to isolate enantiomers just to assign the spectral data.

    3. Separation techniques (chiral resolution), while requiring some experimentation to find the parameters (like ANY purification), are well known. When I needed to do one in graduate school, I went to the library– it’s not very hard.

    4. While it is impossible to predict the individual/relative properties of each enantiomer in a mixture, the properties of the mixture provides a pretty good indication of each enantiomer’s activity.

    5. The CAFC’s opinion weaves immaterial facts into a story that is very slanted in favor of Sanofi. Even then, the Court must rely on very soft arguments, so (as Gideon indicates above) I believe that the Court sought after a way to uphold the patent. Otherwise, I must believe that they are just not very bright.

    This brings me to my real question: Why did the Court decide the case this way? Does the CAFC really have an agenda?

    I apologize for being naive on this point– it’s not taught in my books.

  11. 89

    Thanks MM. Didn’t realise that the facts are different. Will have to read the Decision again. Am not a pharma specialist, so can’t comment on your other remarks (but others just might, I guess).

  12. 88

    MD “If the earlier patent names the enantiomer and reports that it is easy to isolate using conventional methods, is that enough to enable it, as a fact? Can’t see it myself.”

    Me neither. But the facts in this case are different, aren’t they, MD? If you don’t think it makes any difference who is making the statements in the earlier patent, then we are probably doomed to disagree about the result here.

    There is much more to be said about this case and much more will be said. Newman has basically laid down a framework by which a pharmaceutical company can manipulate its internal research program to render accidentally or inappropriately disclosed subject matter patentable.

  13. 87

    If the earlier patent names the enantiomer and reports that it is easy to isolate using conventional methods, is that enough to enable it, as a fact? Can’t see it myself. When you write “It’s easy to lift yourself off the ground. Just use the conventional wing-flapping method” that doesn’t enable flying. The prior patent might be insufficient, but that’s another matter. The patent in suit might be insufficient, but that’s another matter.

    And anyway, isn’t this case more about the burden on an Appellant to get over the high hurdle of “clear error” at the first insrtance?

  14. 86

    If I take a piece of paper with an enantiomer on it and draw an isolated version, then I infringe. That’s pukeworthy garbage. Who could have predicted that?

  15. 85

    “only it and it’s match together was “old””

    Not true. Sanofi’s prior publication discloses each of the enantiomers and the mixture as Sanofi’s “invention.”

    It turns out Sanofi was full of crap. But “technically speaking” they did apparently disclose the isolated enantiomer and “technically speaking” they did admit that if you “desired” either enantiomer and you were skilled in the art, you could simply “separate” them. So conceptually the isolated enantiomer is anticipated. All that’s left is showing “possession” (ie. enablement) and my humble opinion is that if you get greedy in your prior app and start calling out **species** as your invention but you haven’t enabled them, well, tough fricking luck. You don’t get to have your cake and eat it too by arguing that what you told the PTO about your invention was baloney so give me a NEW patent.

    And yes, of course that is sufficient TSM to isolate the enantiomer. The arguments about the lack of motivation in Newman’s decision are pukeworthy, to say the least.

  16. 84

    “to find out how something old can still be unobvious, ”

    Technically speaking the isolated whatchamawhat wasn’t “old”, only it and it’s match together was “old” along with a discussion that you may seperate them. That’s a M for a TSM if I’ve ever seen one. A strong enough M imo to overcome the unexpected results.

  17. 83

    Hey Mr Mooney, I love that last sharp comment on enablement and anticipation. Still haven’t yet read the Decision but will now do so with added interest, to find out how something old can still be unobvious, and exactly how the patent survived the Apotex invalidity attacks. Must say, I’m wondering whether any of the Apotex lawyers reading this blog are feeling in any way embarrassed (or uneasy).

  18. 82

    Noise

    Sorry I got so defensive.

    I think the problem is I can look up the U.S. Code or the Maryland Code on Westlaw, but the NFL Rules are a lot harder to find so we can interpret them ourselves. I’ve read directly contradictory statements about what the NFL Rules actually say, from sports writers I don’t regard as idiots. So I don’t really know.

    You have my empathy as a Browns fan. It’s how I felt last season as a Ravens fan. I think the coach getting fired is also likely to repeat itself, but your GM may also get the axe.

    And I’m really glad I didn’t bet on the Steelers against the Chargers. It really makes me wonder if there’s a scandal like the NBA version (Donahy, I think?) lurking out there.

    About enablement–I can understand how that would change the argument if the claim were for a process of isolating or manufacturing the enantiomer, but is that still true for the composition of matter?

    MM

    I agree. It raises a question, will there be en banc review? It’s not like a circuit split, because if this decision stands, future panels will be bound by it until the en banc court says otherwise.

  19. 81

    smashmouth “I think everyone agrees the original patent was valid. The problem is that it disclosed the enantiomer, spelled out nearly all of its properties, and the isolation procedure was well known to a PHOSITA. The added, lucky benefit that performing this particular, routine separation would also magically separate the desirable from the undesirable properties was a nice accident, but not, standing alone, sufficient for patentability. (Although obviously many of you disagree.) Is this at least a fair characterization of the argument?”

    It’s pretty close. In response to Noise’s complaint, the problem defending this position on enablement grounds is that Sanofi admitted that the the enantiomer was enabled — at least for anticipation purposes — when they described it as their invention in a prior art patent and stated that “if one desired” it could be separated from the mixture. Did Sanofi lie to the PTO when it prosecuted its earlier patent?

    Remember: the CAFC has already held that if you trash a method as inoperable in a prior art patent, that’s not enough to find the disclosure non-enabling. Now Newman says that when you describe your “invention” in an earlier patent and discuss how easy it is to isolate (were claims on the isolated enantiomer filed in Sanofi’s earlier case — I’m guessing yes) it’s NOT enabled for anticipation purposes.

    Apotex got shafted. En banc can fix this.

  20. 80

    smashmouth,

    Unfortunately, sarcasm does not travel well in blogs. I apologize for the nastiness (I should have thrown in a ;-p emoticon).

    Why did Pereira throw in his comment? Good question. Why did the ref’s completely blow the call on the earlier Pitssburgh game with the interception return for a touchdown on the final play (which cost pletnty of people as those points were crucial for the spread)? Another good question.

    Some of these questions I don’t have answers for. I do have answers for questions about the rules and related ambiguity/non-ambiguity.

    In addition, my frustration over the pitiful play of my Cleveland Browns has me in a foul mood.

  21. 79

    Noise

    Why then did Pereira (Chief of NFL officials) confirm that the ball had to break the plane?

    You don’t have to get so nasty. I’m trying to listen and understand your arguments. Don’t assume I’m in the p-ss-ng match that some other posters engage in.

  22. 78

    smashmouth,

    “Is this at least a fair characterization of the argument?”

    No, it is a patently one-sided regurgitation which omits one sides’ key points (e.g. enablement) to try to create ambiguity where none exists.

    What really torques me is that you apply this same poor reasoning to the highly important game of football and instead of merely acknowledging your error, you hide behind “Here I’m only relaying all the conflicting mish-mash I’ve heard from assorted sports commentators.”

    Please remove “football” from your moniker.

  23. 77

    step back

    “No. Instead you could have come to the party room in the dorm where Mooney & friends hung out 30 years ago and simply asked them, “What’s the next great thing in pharmacology?”. They would have stopped puffing on their hookah pipes for a moment to stare at you incredulously and say, “Why obviously by isolating enantiomer X with separation technique Y you get improved therapeutic result Z in 98% of all patients, and by the way here’s the formula for the universal cure to cancer. Now go away.”

    Don’t you think this is a straw man? I think everyone agrees the original patent was valid. The problem is that it disclosed the enantiomer, spelled out nearly all of its properties, and the isolation procedure was well known to a PHOSITA. The added, lucky benefit that performing this particular, routine separation would also magically separate the desirable from the undesirable properties was a nice accident, but not, standing alone, sufficient for patentability. (Although obviously many of you disagree.)

    Is this at least a fair characterization of the argument?

  24. 76

    UK Chemist

    From the overall tone of your contribution I thought you were in the anti-group. Now I see that I was wrong – sorry!

    I don’t support either side of the argument. Simply realizing that courts decide cases according to the evidence – which in that case was very detailed and interesting.

  25. 75

    This is for “Do you really think you have anything to teach Judge Newman about gloves or optical isomers?” Paul.

    Thanks for putting me in my place… but did you not notice that I was in fact agreeing with Judge Newman?

    I’m not sure how you came to the conclusion that I was trying to teach her something. Rather, I was just trying to put the scientific concepts behind the ruling into more general terms for any non-chemists.

    Although your comments were certainly packed full of sarcastic wit, I’m struggling to see what point you are trying to make… Could you clarify?

  26. 74

    This is for UK chemist.

    A court has to reach its decision on the evidence before it and on the arguments of counsel. Not on the basis of its prior education, on prejudice,or on what the judges read in the newspaper yesterday. Any party to any proceedings will quickly realise how important that is – it is an essential aspect of due process.

    So if you want to see the evidence on which Judge Newman and her colleagues reached their decision (it was a three judge court, not Judge Newman on her own), you should read the opinion, because that is where the evidence is set out. You may, of course, know differently what a skilled person would have done, but unfortunately you were not engaged to testify before the court and the court did not have the benefit of your greater knowledge. And even if you had been in that position, you would inevitably have found yourself deposed or being cross-examined by opposing counsel, and you might have found that your knowledge was nowhere near as detailed and relevant as you thought it was. So count your blessings that you did not have to stand up before a judge, opposing counsel and a stenographer and have your knowledge tested.

    If the judges had thought that the evidence being adduced by either party was egregiously wrong, they might, and probably would, have asked questions of counsel and/or the expert witnesses. But apparently this did not happen, and the evidence in the case was believed.

    Do you really think you have anything to teach Judge Newman about gloves or optical isomers? If I guess right, she knew all about them years, if not decades, before you were born. And besides, the parties in court were no doubt fighting with their gloves off.

  27. 73

    The only inventions worthy of patents are dynomite (as Jimi JJ Walker), the transistor, MRI and the Gatling gun. The light bulb should never have been patented under KSR standards. There were too many attempts using different filaments, and the one used would have been obvious to try. Heck, maybe the other ones too!

  28. 72

    UK Chemist,

    You’ve wasted your time.

    By that, I mean spending all those years going to school to study undergraduate chemistry and then to get a PhD in some esoteric branch of chemistry and then to spend all those years doing actual research, coming up empty handed with 99% of your experiments but having the resolve to keep going and to try again and again until one day you can finally shout, ‘Eureka, I’ve found it’, all to your lonely self at 2AM in the morning in an empty lab and then to find out the next day that your ungrateful boss is firing you because you are not economically productive enough in his bean counting mind.

    No. Instead you could have come to the party room in the dorm where Mooney & friends hung out 30 years ago and simply asked them, “What’s the next great thing in pharmacology?”. They would have stopped puffing on their hookah pipes for a moment to stare at you incredulously and say, “Why obviously by isolating enantiomer X with separation technique Y you get improved therapeutic result Z in 98% of all patients, and by the way here’s the formula for the universal cure to cancer. Now go away. Can’t you see I’m busy doing much more important things here. Dudes, let’s keep partying on and being most excellent as well as totally like omniscient.”

  29. 71

    “Everybody who has made it through 8 weeks of O chem understands that stereo isomers almost always have different biological effects. It’s the classic right glove left glove model. The right glove will keep your right hand warm – the left glove won’t.”

    Ok. So previously, in order to keep your right hand warm, you’ve been wearing both gloves and (as they are made of wool or something) they are pretty itchey…

    Then you find that using just the right glove keeps your right hand warm… (pretty obvious)… but also that, when you use just the right hand glove, it doesn’t itch… pretty unexpected!! There you go – unexpected benefit from using just one. Couple that with the fact that (for some crazy reason) the gloves were a real pain in the ar3e to seperate, and you’ve got an invention.

  30. 70

    OMNI was “an original if not controversial mixture of science fact, fiction, fantasy and the paranormal”

    Mooney wrote articles for us all the time, it was no big deal.

  31. 69

    Max, yes Chemistry is considered among the unpredictable arts. However, if you are as gifted as Mooney, everything is predictable and you are gifted with omniscience, which is not to be confused with omni-science, which was a futuristic magazine from the 70s.

  32. 68

    I submit that everything that can be invented has been invented.

    What kind of garbage is it that some scientists are saying that a mundane crystal can be “excited” with a simple electrical charge and produce a “coherent beam of energy?” Why this was thought of years ago by that Greatest of all Inventors in the form of sunlight. Why if you took a piece of paper and drew a crystal and put some wires on the crystal you would have the same thing.

    Worthless garbage.

  33. 67

    6: here in Europe you don’t get anticipation till the state of the art includes a disclosure that is enabling. Sometimes it is unknown how to separate the enantiomers. PHOSITA knows they exist but not how to get at them. How is it in the USA, with anticipation, in the field of enantiomers? I assume that in the USA, chemistry is unpredictable and physics/engineering are predictable, just as they are here in Europe. I assume therefore that patentability in chemistry in the USA is different from that of ME/EE, just as here in Europe.

  34. 66

    I will give credit, Mooney demonstrates a great capability of sounding like he might know what he’s talking about. However, upon close review, it is clear that he is only good at reading and regurgitating other people’s opinions and inserting generous references to excrement and other unmentionables.

    The result is worthless annoying garbage.

  35. 64

    “Save your tears, troll. Next year is going to be a lot worse.”

    Does this mean you are going to be even more glib and annoying next year?

  36. 63

    If you knew half as much as you thought you did about patent law Mooney (which is dick/2) you would not be spending all your time annoying patent attorneys. You would actually be doing something constructive to earn a living.

    I submit that you, my good sir, are the only troll around here.

  37. 62

    “The only issue, then, was to determine whether the one skilled in the art could purify the enantiomer without undue experimentation.”

    Not really, clear anticipation is clear anticipation. Enablement comes easy, especially here where the method even the applicant used was well known and likely to work. If the newer application claimed a method of seperating the two and getting the one then PERHAPS you could say it was non-obvious. I haven’t looked at the claims, but if they claimed only the single whatever it is then if the single whatever it is was already mentioned in the art with a reference to it being isolated then that’s clearly enabled anticipation it looks to me like.

    But then, the facts could be different than any of us really know about, we just read the decision, we haven’t read everything related to the case through and through.

  38. 61

    Thanks Mr Cole. You say that EPO reasoning is not the way the courts reason. I agree, and think it a shame. Ah well, at least Lord Hoffmann in the UK Supreme Court defers to EPO law when it is “well-settled” (even if the German Supreme Court does not), and there’s nothing more settled at the EPO than its 30 year old unassailable Problem and Solution Approach to obviousness. So there’s hope yet, I feel

  39. 60

    “Yes, its about as annoying as I am when I do exactly the same thing, pretend everything is clear-cut and post meaninglessly glib, one sentence retorts.”

    Save your tears, troll. Next year is going to be a lot worse.

  40. 59

    “What you now have is a fairly comprehensive library of gene sequences that correspond to genes that are active in that cell type. Anybody who doesn’t understand the utility of that is either an id1ot or a non-biologist.”

    Too bad that “corresponding to something useful” isn’t the standard for patentability. Then a CD with a bunch of dents in it would be patentable. Oh wait …

    Like I said: not for long.

  41. 58

    “The most annoying thing about this decision is Newman’s pretending that the result is clear-cut once you apply “the law” correctly. ”

    Yes, its about as annoying as I am when I do exactly the same thing, pretend everything is clear-cut and post meaninglessly glib, one sentence retorts.

    “If Apotex is smart, they hire some decent appellate lawyers, take this thing en banc, ”

    If I was smart, I’d realize that an en banc rehearing is not a matter of right. Therefore there is no such thing as “taking this thing en banc,”

    “This decision smells funny”

    Oh wait, that’s just me.

  42. 57

    The most annoying thing about this decision is Newman’s pretending that the result is clear-cut once you apply “the law” correctly. A better decision would note that the case is close and it comes out Newman’s way (the wrong way) only because (as usual) someone is making up some new law on the spot to reach the desired result and make it sound oh-so-correct.

    There is no honest dispute as to whether Sanofi’s claimed isolated enantiomer was disclosed in Sanofi’s previously published application. It surely was. Sanofi came right out in their application and said the isolated enantiomer was part of the inventon and all you had to was separate it from the racemic mixture if you wanted to.

    The only issue, then, was to determine whether the one skilled in the art could purify the enantiomer without undue experimentation. Actually, the CAFC has made it very clear over the past few years that the hurdle for finding enablement of a prior art reference, particularly a patent, is lower than that for enabling one’s own claim. In fact, the CAFC has said that even an express teaching in a prior art reference that an invention does not work is not sufficient to find the reference non-enabling for anticipation purposes.

    But here we have Sanofi itself talking about its OWN invention of the isolated enantiomer and STILL Judge Newman and the District Court judge decide to swallow Sanofi’s expert’s testimony. So your self-serving testimony is enough to contradict your self-serving boilerplate, apparently. Is it possible to eat the entire cake and have it, too? Apparently. Pay attention to the magic words that allow applicants to describe a composition species as their invention and later (after it becomes 102(b) art) to obtain a patent over that description. The magic words are: “if one desires …”.

    As for the obviousness analysis, it’s too bizarre for words. Again, Sanofi describes the enantiomer as their invention in a 102(b) reference and says that one need merely separate out “if one desires.” And later Sanofi trots out their experts to argue that there was not even a **reasonable** expectation that one of the two entantiomers in this racemic mixture that they had spent years studying would be useful? Newman makes it sound like it was a crazy daring adventure to purify the enantiomer. Except there’s the unfortunate existence of the Sanofi memorandum explaining exactly why Sanofi might decide to spend a lot of time purifying the enantiomer. Kudos to Newman for even mentioning the memo, although why it was appropriate for her and the district court to give the memo “short shrift” remains baffling and probably always will.

    If Apotex is smart, they hire some decent appellate lawyers, take this thing en banc, and do it right this time. I might even toss in some novel equitable arguments. This decision smells funny.

  43. 56

    Dennis wrote: “The difference is that an isolated EST fragment is good for nothing except *maybe* binding to its complement. No unexpected properties. No nothing. It’s non-creative doo-doo.”

    Oh Dennis, nice try, but, unlike the others here, I don’t have any buttons for you to push! FAIL!

    EST fragments are good for nothing? Obviously you’re not a BIO guy. That’s ok. Most of the patent bar are not bio guys.

    Let me help you out . . .

    You take an unexamined organism. You do the well known whammy treatment to RT all the mRNAs in a particular cell type. You get out a bunch of ESTs.

    What you now have is a fairly comprehensive library of gene sequences that correspond to genes that are active in that cell type.

    Anybody who doesn’t understand the utility of that is either an id1ot or a non-biologist.

    Dennis, in MM hat, wants to try to get past the utility argument by going right to “you need to show me unexpected results.”

    No I don’t.

    Once I show you utility, which I have, now you have to explain to me why it is that sequencing any old gene is somehow different than sequencing an EST.

    The answer? There is no difference! Neither requires “unexpected results”!

    So, knowing that, the PTO had to cut off ESTs before they got to that stage. What’s earlier than that?

    Either patentable subject matter or utility.

    The PTO went with utility because it would be awkward to construct the pretzel about why it is a 300 base pair segment that is discovered in nature and that codes for a protein is patentable subject matter while a 290 base pair EST that codes for 29/30ths of the protein is not.

    UTILITY!! GUffaw1!! haawawawawahaawahaaaw.

    No, there’s no utility in ESTs – companies today routinely create them just to waste money. Haw haw.

  44. 55

    What I find interesting is the assertion that I know too little — apparently for this class of chemicals, someone skilled in the art would not expect a benefit, that they are in some way different from thalidomide, naproxen, fat/olean, and so on; that that though it seems obvious to me, if I only knew the field well, it would then become non-obvious. This is a peculiar sort of “obvious”. I am certainly aware of people outside a field making nonsensical suggestions, but this appears to be analogous to someone in my field (computer science) doing “X, but with another level of indirection” or “X, with a cache” (caching, indirection, and binary search being the building blocks of an extraordinary amount of computer science) — of course you consider adding a cache, of course you consider adding (or removing) a level of indirection. Separating a biological compound into its isomers sounds like something that you would attempt whenever possible — if nothing else, you cut your risks in drug trials. The separation technique may be tricky, but it doesn’t sound like that is what was patented here.

  45. 54

    “and to provide a small course correction to the CAFC”

    LOL, like “THERE’S AN ICEBURG AHEAD, FULL ASTERN!” is a small course correction.

  46. 53

    “After KSR, “obvious to try” is sometimes enough to invalidate a patent, but not always.”

    The point of the “obvious to try” discussion in KSR is to punch the strict-TSMers in the face. An express motivation to combine does not need to be found in the art.”

    All this face-punching, excrement, and personal hostility. Mooney you are a sick puppy. I really pity those in your personal circle. Perhaps those of your glib attitude need the Federal Circuit to punch them in the face.

    KSR simply confirmed that which was always the case. TSR requires a motivation found in the references themselves, or “in the knowledge generally available in the art.”

  47. 52

    “if you read KSR it was a careful and deeply conservative decision. Its purpose was to reverse on the facts and to provide a small course correction to the CAFC”

    KSR was not a small course correction. There were a lot of patents being issued that issued primarily because applicants insisted that Examiner’s “point” to express language in the art that taught the claimed combinations. Essentially, applicants were attempting to turn obviousness into an “anticipation light” analysis.

    The Supremes crushed that concept under their boots without any ambiguity. This was not a small course correction to the CAFC. It was a large enough correction that the CAFC began reversing itself prior to the KSR opinion because they could see the writing on the wall.

    The only thing left is for the USPTO to get quality examiners into the software and computer art units and start applying KSR for real (and not buckling under bogus “analogous arts” arguments).

  48. 51

    This is in answer to the Max Drei question.

    Aspirin was a brilliant German invention.

    It provides a solution to the treatment of headache and a range of other disorders.

    But if you want something to fill into sandbags as a flood defence, it is no good whatsoever. It is too low in density to be an effective barrier, and it is water soluble. Sand is a much better material and was already available for the purpose. I don’t think aspirin is much good as an electroluminescent material in organic light-emitting diodes (OLEDs) either.

    We could say that if we are giving a per se claim to a new chemical compound then the utility should be commensurate with the claim scope and the compound must be useful for all possible purposes, otherwise the claim is invalid.

    That is not the way that the courts reason, however. Occasionally the EPO explicitly finds a narrow field of endeavour for a new chemical compound even though a per se claim must cover all possible fields of endeavour. Pragmatism rules over pure logic. Whether that is a good thing, or intellectually honest, I decline to speculate at this early hour of the morning.

    Malcolm: You say “The point of the “obvious to try” discussion in KSR is to punch the strict-TSMers in the face.” I am not a US citizen so I do not know the Supremes as well as you folk do. But I don’t think that any such intention can or should be attributed to the Supremes. I was not aware that the judges of the Supreme Court had a reputation for gratuitous physical violence, but perhaps you know better! Moreover, if you read KSR it was a careful and deeply conservative decision. Its purpose was to reverse on the facts and to provide a small course correction to the CAFC in ways in which it was acknowledged in the decision the CAFC had already decided on. It was plainly not intended to create an over-reaction, and it is dangerous to hang on every word of the judges and read too much into the minutiae. The over-reaction comes from others e.g. the USPTO.

  49. 50

    Max, I think I follow your argument.

    Where we claim an enantiomer per se, we do not limit the scope of protection, therefore a claim to the enantiomer per se, when a racemate is known per se, should be obvious?

    Under this argument a claim to the enantiomer for the treatment of a disease seams also to be obvious, if the racemate is known to treat the disease.

    The only argument left appears to be the unexpected technical effect that is achieved. But as I pointed out above, you might believe that this is a free bonus, that you arrive at when you follow the general teaching, to make the enantiomers of any racemeic compound and find out whcih one is the active one……..

    Its getting late! (well in Europe anyway!)

  50. 49

    By the way, if I’m the judge the case is over as soon as I see these words in Sanofi’s prior art patent specification:

    “These compounds having an asymmetrical carbon may exist in the form of two enantiomers. The invention relates both to each enantiomer and their mixture.” ’596 patent, col. 1, lines 39-41.

    That’s it. Case over. It’s one thing for someone else’s patent to be found non-enabled for some greedy grabby language. But your own prior art patent? It is a sad joke when applicants get to have it both ways but that’s what happened here.

    Judge Newman blew it again.

  51. 48

    Thanks Astacus, but I’m not making myself clear enough. Enantiomer X_left is novel, but is it non-obvious? That seems to depend on whether it’s a cure for disease Y. I’m in the “first medical indication” zone, rather than the “second medical indication”. Intuition tells me that the enantiomer (X_left), as a thing per se, ought to be declared obvious, when the racemate (X_left and right) is old. But not a claim to X_left as a cure for disease Y. That’s my second attempt, to get across what I mean.

  52. 47

    “Dennis, I’m going to hand this one to you. I love your blog, it saves me time, which means $ in GP’s pocket, and you seem like a swell guy.”

    And that is why D could charge admission to the site.

    “The only thing that could possibly make it any more inhuman would be for the same company to be vested in both the cancerous faggots and the patches and gum.”

    I’m totally going to start a company called 6k Inc. It’s sole purpose will be to invest in PM USA and Nicorete. This will be full of lulz.

  53. 46

    Max i appears to me that the difference springs from the EPO problem solution approach to obviousness. The invention of the new compound was brought about by the skilled chemist looking for the solution to new drugs to treat disease X.

    Drugs were available to treat disease Y but these would not have informed his strategy because there was no teaching that modifying these compounds would lead to a drug for disease X, even if the solution compounds were virtually identical to those for disease X.

    In the US the Examiner would tell you that one would have been motivated to make the new compounds because they were so close to the compounds for treating disease Y that the skilled worker would have expected them to be useful to treat disease Y.

    At this point the EP attorney starts to pull his hair out and say “but I don’t want to treat disease Y, I want to treat disease X……”

  54. 44

    I got to this thread rather late by the looks of it. Never the less, I would like to add my two pennyworth on the enantiomer decision, and its this:

    Normally in an enantiomeric separation one finds that activity will follow one enantiomer. This is the clear motivation to do the experiment and expect to put your hands directly on the prize. If, fortuitously, you also find that the tox goes the other way, this is a freebee, a bonus, that you would have found anyway, had you done the experiment that anyone skilled in the art would have done.

    The key therefore appears to be that the prior art of this specific area suggested there would be no benefit in doing the expeiment in this particular case.

    As for ESTs being unpatentable. Good decision in my view.

    The only utility for an EST of a gene of unknown function is to use as fly paper to catch some poor dude who has actually done the hard work and made the real invention.

    EST patents give patents a bad name.

  55. 43

    “If they allow ESTs – which are really nothing more than gene fragments, and therefore indistinguishable from gene patents other than for the completeness of the sequence”

    LOL. Dude. Sometimes it helps to read what you write before hitting the “post” key.

    The difference is that an isolated EST fragment is good for nothing except *maybe* binding to its complement. No unexpected properties. No nothing. It’s non-creative doo-doo.

    For what it’s worth, if you do some more work to show that a novel EST or a novel collection of ESTs provides some unexpected results, you can get a claim out of it.

    It’s a relatively grown-up practice.

  56. 42

    Paul Cole, are you still there? I have always wondered whether there is a disconnect between “absolut Stoffschutz” (absolute protection for substances) and EPO-PSA. In other words, to defeat obviousness, you can pray in aid the unexpected technical effect of Molecule X against Disease Y, but only when you claim “Medicament against disease Y, characterized by Molecule X”. If you reach further, and claim “Molecule X” as such, you haven’t “solved the objective problem” so shouldn’t be allowed to invoke the unexpected technical effect, and furthermore, your technical field is nothing more than “molecules” and in that field the enantiomer “as such” is indeed obvious (as contributers above are urging). Following my line would overturn about 40 years of chemical jurisprudence in Germany and upset all the chemists (except those who were in practice before the 1960’s). But it might help the rest of the world to accept that the patent system is capable of awarding a scope of protection commensurate with the contribution. In the long term, that acceptance will be quite important, to our clients, innovative industry.

    Paul, where’s the flaw in my thinking, please?

  57. 41

    MM – you’re too smart for that. 1st, megacorps don’t research genes that are trivial. 2nd, albeit it’s been a few years, I never got a “trivial” rejection on the hundreds of gene apps I prosecuted. Ever.
    2nd – if you’re citing KSR for support, cite the CAFC case that supports your proposition that the standard for gene patenting has gone up relative to pre-KSR.

    Regarding EST patents – ah yes – ESTs, near and dear to my heart.

    Dennis, I’m going to hand this one to you. I love your blog, it saves me time, which means $ in GP’s pocket, and you seem like a swell guy.

    I authorize you to use this for a neat paper – whatever.

    Gene patenting was and always has been WRONG as a matter of public policy and as a matter of subject matter.

    Patenting genes is nothing more than patenting something that exists, that you discover, and that required zero inventive input. The patent system, guided by – TBTB – granted patent rights for discovered genes because it would be a boon to large corporations. Like I said before, J6P doesn’t apply for gene patents.

    So then some bright bulb gets the idea of filing for a patent on ESTs.

    The rationale given by the system for not allowing EST patents was some nonsense utility argument.

    Of course ESTs have utility! Of course they have value! The fact that so many EST libraries exist is proof enough of that. The fact that companies invested lots of money in IDing ESTs is more proof of that. EST’s are expressed. That means that, almost without exception, an EST represents a marker to protein functionality. Knowing that has value.

    But the patent office was in a quandary. If they allow ESTs – which are really nothing more than gene fragments, and therefore indistinguishable from gene patents other than for the completeness of the sequence, then, unlike genes, which take time to work out, they would be faced with these crazy “inventors” banging out EST libraries in a relative blink of the eye, thereby locking down whole genomes and the gene booty that would inevitably follow.

    This was the unintended consequence of permitting patents on isolated genes.

    So it had to be stopped. If it wasn’t stopped, the consequence would have been an unmitigated race to compile and file EST libraries. To the winner would go all subsequent gene discoveries in the genome for which the EST library was compiled.

    Imagine! Compile an EST library for human liver and file on every EST that you find! A 20 year monopoly on all human liver genes. Anybody finds a new gene with a new use, they gotta come hat in hand to you to do anything with it.

    So the solution was not to continue the “inventive” gene facade.

    The solution was what? “Lack of utility”?

    Hahahahaahahahahah.

    That’s really the best the PTO could do?

    What they didn’t want to do is confirm that gene sequences, whether in whole or in part, should not every have been considered patentable subject matter.

    If ESTs are not PSM, then why would genes, which, are no different in “inventive concept” than are ESTs?

    Bottom line, ESTs are as patentable as complete gene sequences, and the full sequence/partial sequence utility/no utility garbage that the PTO came up with is just one more brick in the wall on which the prophet’s words are written:

    “The Patent System is a Joke.”

  58. 40

    Gideon, there is some truth to your rant, but the fact is that the USPTO and the courts have been far more conservative with their business-promoting decisions relating to the biotech industry than they have been with the so-called “high tech” industries. See, e.g., Beauregard claims for a quintessential example of a nonsensical purely political handout that benefitted applicants and trolls but ruined the USPTO. Beauregard claims make expressed sequence tags look like pure gold. But ESTs were nixed (and rightfully so) as trivial unpatentable crap. Everybody in every art unit and the public benefits from that decision. The only people who don’t benefit are those unfortunate gamblers who were filing ten thousand EST patents a month and betting that they would be worth a ton of cash.

  59. 39

    Gideon “This is much like DNA – simply patenting what is known because you isolated it.”

    What? You can’t simply patent a known DNA molecule by isolating it. It needs to have a non-trivial utility and (after KSR) unexpected properties.

  60. 38

    Just read the case – how boring and predictable. CAFC wants a certain result, so they get it. Results-oriented judging – gotta love it.

    This brings me back to Chakrabarty. Some people were arguing that an engineered plasmid shouldn’t be patentable. I’m sitting there thinking – huh? What is this, a religious argument? What is an invention if not the manipulation of genetic material into new forms?

    Then, somewhat later, I find out that a gene sequence that occurs in nature can be patented if it is “isolated.” So I ask the partner for whom I’m working, “I thought that it was patent theory 101 that you couldn’t patent discoveries. Isn’t this just discovering a gene sequence?”

    I get all the BS CAFC law on DNA in return.

    I then propose that I’ll write a paper arguing that DNA patenting was set up and has been propagated by big corp, and that’s it’s ridiculous to be handing out patents on the first lab rat to sequence gene Z.

    Partner’s face screwed up, turned red, and just about popped. Whoops. New associate doesn’t understand that we work for Fortune ### company that makes whole heapum money on gene patents.

    That’s when I first started to realize that the patent system was a joke.

    This decision is just one more solid brick of evidence in the wall of the facade of patents.

    Patents are for the big boys. Little boys don’t get patents. Big boy wants a patent on a known enantiomer? Where the structure has been explicitly provided in the prior art, and the usefulness of the molecule has been touted?

    No problem. We’ll give you another 20 years of profit.

    The best part is the circularity of the whole thing.

    Eat too much garbage food pimped by corporations, need to take medication pimped by other corporations, so you can continue to eat garbage food pimped by corporations.

    Gotta love Americana.

    Only in America could you have a company that sells deadly, addictive, cancerous substances that also has ‘stop smoking’ assistance hotlines and programs.

    The only thing that could possibly make it any more inhuman would be for the same company to be vested in both the cancerous faggots and the patches and gum.

  61. 37

    Gideon “The fact that, after separation of the enantiomers, they got an uncommon result, is meaningless.”

    The legal term is “unexpected”. And to some extent, I feel your pain. This case might have come down the other way and it wouldn’t have been a surprise nor would it have been the End of the World For Pharmaceutical Patents As We Know It.

    The fact is that our patent system does reward people who do obvious things but get “lucky” because the end result is unexpectedly awesome.

    Strangely, it also rewards people who file tons of vague computer-implemented junk which achieve silly pointless crap like entering one’s TV preferences into an object-oriented database (wow!!!!!!) or changing the order of a list with a single click (OMIGOD!!!!!!!). Of course, in this latter case, the reward comes not from luck or ingenuity but from manipulation of the system and braindead examiners.

  62. 36

    Gideon

    I agree with your proposed rule, but I can hear the howls from some of the opponents already.

  63. 35

    Noise

    I’m aware of the rule you’re citing, but sometimes (just as in legal matters) what someone thinks is unambiguous is construed differently by a court (or the refs). Here I’m only relaying all the conflicting mish-mash I’ve heard from assorted sports commentators. Anyway, I thought it was interesting that Coleman, at the game, made an obvious reference to your interpretation, but appeared to backtrack at a post-game press conference, where suddenly he claimed to have seen that the ball had broken the plane. I’m waiting to hear Pereira explain how the league interprets the rule. All I know is that in more than 40 years of watching the NFL, I’ve never seen this play. Ususally the ball carrier’s feet are short of the goal line and he reached across with the ball, or it’s unclear if the receiver’s feet came down in the end zone. And Coleman’s interpretation is consistent with the touchback rule. I’m just telling you I’m not 100% certain what the rule is, and I’m not convinced the refs did either.

  64. 34

    I’ve give you a bright line test –

    An isolated enantiomer is ALWAYS obvious over the disclose racemic mixture.

    The folks who like to patent known structures are forced to talk about “function” and “unexpected results” and “toxicity” and how, “wow, the one worked to cure X and the other killed bald guys.”

    All of that is garbage and a distraction.

    Everybody who has made it through 8 weeks of O chem understands that stereo isomers almost always have different biological effects. It’s the classic right glove left glove model. The right glove will keep your right hand warm – the left glove won’t.

    The question of obviousness, in this case, has nothing to do with function. It only has to do with what is already known and disclosed. The rest of it is just haze thrown up by the Pharma industry to make money.

    To take a known racemic mixture, where it is already understood that one of the enantiomers has a use, and then separate them, is as obvious as water is wet.

    Any reg number monkey discussing “function” has lost the forest for the trees.

    The fact that, after separation of the enantiomers, they got an uncommon result, is meaningless.

    This is much like DNA – simply patenting what is known because you isolated it.

    Classic patent law Corporate fodder – add the word “isolated” to a naturally occurring DNA sequence and, wow, there’s an “invention”. Well, only if big Corp can make money on it! Not too many Joe 6Packs running sequencing gels or spinning out racemic mixtures in his basement!!

    Oh and Dan – I’m like a floor Trader – I don’t care which way the market goes – I’m a gunnuh make my coin.

  65. 33

    anonymous at Dec 15, 2008 at 12:14 PM,

    Thank you for the link. Without being too precise, I was intimating something along the lines of Paul Cole’s post (Nicely done Paul – thank you).

    Smashmouth,

    You might need to remove the “football” from your moniker. The NFL touchdown rules clearly state the requirements in the alternative. There is no ambiguity for you to hang your hat on (at least in the rules – personally, I think the call was bogus because I did not see conclusive evidence that the receiver actually did get his feet down after catching the ball – the Raven hit did not cause the receiver’s feet to elevate and the receiver appeared to land outside of the endzone). Be that as it may, you are correct, there is no appeal.

  66. 32

    Question: if the single enantiomer had been isolated and was no more active or only a few percent more activity than the mixture of the two enantiomers, and had some of the same side effects as the mixture, should it be patentable?

    Answer: No.

  67. 31

    Malcolm, I think you’re confusing the sort of hindsight analysis disapproved in Graham and KSR with the inevitable fact that litigation over whether an issued patent is obvious comes AFTER the invention date.

  68. 30

    “The job of the court, assisted by the expert evidence, it to put itself in the position of the research manager faced with that decision [What is best done with your precious research dollars, and how are the available routes for further development to be prioritised] just before the invention was made”

    That’s utterly false. And you know what else? It’s an example of a sort of hindsight that is just as bad as the kind discussed in KSR.

  69. 29

    “After KSR, “obvious to try” is sometimes enough to invalidate a patent, but not always.”

    The point of the “obvious to try” discussion in KSR is to punch the strict-TSMers in the face. An express motivation to combine does not need to be found in the art.

    Let’s say you visit Ibwamaland and find some person in the market selling a food paste made from zogonuts. In Ibwamaland, they spread the paste on a flat piece of bread made from dog toenails.

    Should you get a patent on a peanut butter and zogonut sandwich just because nobody specifically taught putting zogonut spread between two pieces of bread before? Here’s an additional fact: the sandwich tastes like peanut butter and zogonuts.

  70. 28

    With reference to the anonymous comment, it is appropriate to quote Judge Newman from the Abbott case:

    “The evaluation of the choices made by a skilled scientist, when such choices lead to the desired result, is a challenge to judicial understanding of how technical advance is achieved in the particular field of science or technology. Such understanding is critical to judicial implementation of the national policy embodied in the patent statute. In Publication of Tomlinson, 363 F.2d 928 (CCPA 1966) our predecessor court discussed the role of “obvious to try” in scientific and technologic research and in patentability:

    ‘Slight reflection suggests, we think, that there is usually an element of “obviousness to try” in any research endeavor, that is not undertaken with complete blindness but rather with some semblance of a chance of success, and that patentability determinations based on that as the test would not only be contrary to statute but result in a marked deterioration of the entire patent system as an incentive to invest in those efforts and attempts which go by the name of “research.”‘

    id. at 931. The Court in KSR did not create a presumption that all experimentation in fields where there is already a background of useful knowledge is “obvious to try,” without considering the nature of the science or technology. The methodology of science and the advance of technology are founded on the investigator’s educated application of what is known, to intelligent exploration of what is not known. Each case must be decided in its particular context, including the characteristics of the science or technology, its state of advance, the nature of the known choices, the specificity or generality of the prior art, and the predictability of results in the area of interest.”

    Judge Newman is quoting the late Judge Giles Rich, and the very same passage has been quoted by UK courts considering the same topic. The consensus here is that “obvious to try” is a test that is sometimes applicable but should be applied with caution and is not a gloss on the statutory standard of obviousness.

    With reference to Max Drei’s comment, it is always useful to study past decisions on a particular topic and they remind us of the evidential lines of enquiry that we should make in order to adduce the evidence on which a court will make its decision. But every case is different, and you cannot rely on a past decision as to an issue of FACT, only the principles of LAW which might be applied to a particular factual situation.

    Put yourself in the foresight situation, imagine you had a limited research budget, and that you wanted to pursue the best possible line of research. Should you continue with the enantiomeric drug which was effective but neurotoxic, should you resolve and test the enantiomers or should you continue to test related compounds in the hope that an even better compound might emerge from further synthesis and testing? What is best done with your precious research dollars, and how are the available routes for further development to be prioritised? The job of the court, assisted by the expert evidence, it to put itself in the position of the research manager faced with that decision just before the invention was made, and this is a factual enquiry whose outcome will differ from case to case. With foresight, there is no way of knowing which is the winning route, or even if there is a route that leads to a better outcome than you already have. If you pay the money and resolve the drug, chances are it may not make much difference, or the human body will be sly and turn the enantiomer back into a racemate while you are not looking. It is only with hindsight that the enantiomer resolution route looks obvious. With foresight it is the expensive gamble that drug research truly is.

  71. 27

    smashmouth: “Wasn’t the utility already disclosed in the patent application for the racemate? I just don’t see why this wouldn’t have been obvious to try.”

    It was obvious to try. And it was fairly routine business of doing it, too. However, it was unexpected that the isolated stereoisomer would have the impressively desirable properties that is has. Unexpected results is the only secondary factor that is worth a darn, frankly, particularly when the results are awesome and intimately related to the use of the compound (as opposed to, say, a finding that the isolated stereoisomer tastes especially good to hamsters).

  72. 26

    Noise above Rules

    Yes, I still do. It’s like a question of statutory interpretation, where the case law has construed an ambiguous phrase. The phrase here has been interpreted to require that the ball break the plane of the goal line. But in any event, the Ravens lost and there’s no appeal!

    anonymous

    Thanks for the link, when I finish work I’ll check it out. Overall, I think KSR isn’t going to resolve or clarify obviousness. It seems to pay great homage to the Graham factors, but those factors have about as much content as Fourth Amendment totality-of-the-circumstances analysis. In other words, we have almost an empty vessel into which the judge, patent examiner, etc. pours their gut feeling.

  73. 25

    smashmouth and Noise,

    After KSR, “obvious to try” is sometimes enough to invalidate a patent, but not always. There’s some ambiguous language in KSR about it, and the latest word from the CAFC is, I think, Abbott Labs. v. Sandoz, Inc., decided in October of this year and–coincidentally–written by Judge Newman. Slip. op. at 7-18.

    link to cafc.uscourts.gov

  74. 24

    Mr Feigelson wanted input from me. I haven’t read the decision yet, and have only skimmed very fast through the thread, but I see Paul Cole is in there, and he knows what he is talking about. Indeed, this thread might reveal how some commentators know what they are writing about, while some of the others manifestly don’t. There is a hundred years of rich history on the patentability of enantiomers, and I suspect that the chemical Boards of Appeal of the EPO (mindful of the high importance to Germany of innovative pharma) have enriched that jurisprudence over the last 30 years, rather than quarrelled with it. Then there’s the English body of caselaw, up to, what was it, Lundbeck, I think. Bear in mind that England has a reputation for trashing obvious subject matter and for balancing the interests of pharma and generics. Yet its caselaw is all pretty consistent, I believe. Those sounding off above would wish to junk all that jurisprudence. I would suggest we just ignore them. Now I’ll read that Decision.

  75. 23

    Smashmouth,

    “Obvious to try” in and of itself is not allowed. The use of that tool is predicated on a number of factors, including, importantly for the field at issue, predictability in the art.

    As for the NFL, yes it does depend on how the league interprets “caught in the end zone”. That’s why I provided the rule the league uses to make this interpretation. Based on that interpretation, the ref got it right. Do you still think that ref blew the call?

  76. 21

    Noise above Rules

    Depends how the league interprets “caught in the end zone.” Anyway, I don’t think it’s obvious. (Couldn’t resist the bad joke.)

    I’m looking forward to Mike Pereira’s explanation.

    Back to the subject. Can somebody remind me about patentability of chemical compounds? I thought (maybe incorrectly) that you could claim the structural formula, novelty, and just some (even weak) evidence of utility. In other words, the applicant wouldn’t have to reveal or even know up front about ALL uses. (And you would have actually had to synthesize it, I suppose. The Pfaff case notwithstanding.) Wasn’t the utility already disclosed in the patent application for the racemate? I just don’t see why this wouldn’t have been obvious to try.

  77. 20

    From the NFL.com rulebook section on touchdowns:

    “To score a touchdown, the ball must be carried across the goal line into the end zone, caught in the end zone, or a fumble recovered in the end zone, or an untouched kickoff recovered in the end zone by the kicking team.”

    Since the ball on the play in question (seemingly) never made it across the goal line into the end zone, I imagine that the ruling has to do with “caught in the end zone”. A player is in the end zone if both feet touch while in possession of the ball(regardless of where the ball is). In overturning the original call, the referee did explain that the receiver was determined to have both feet down in the endzone while in possession of the ball; the play is properly judged to have been “caught in the end zone”.

    The Refs got it right.

  78. 18

    anonymous

    A few hours after I posted that comment, after my temper cooled, it occurred to me how unlikely it would be for the Supremes to grant cert in this case, for the reasons you explained so well. The specific issue is too narrow. And both lower courts applied the current test, even if I think they did so incorrectly–but that’s almost never a cert question. (Although in habeas cases you’ll see the Court decide cases where the issue IS whether the lower court correctly applied a settled legal standard. But these are often capital cases, and they generally involve areas of the law where the Court simply is more knowledgeable than in patent law. In any event, I don’t claim expertise in Supreme Court practice, but my observation is the Court prefers to take cases where the law is unsettled, rather than a mere assertion that a lower court incorrectly applied a settled standard.)

    (Disclosure–I’m still not thinking clearly because I’m so pissed off the refs gave Pittsburgh that touchdown–talk about ignoring a standard of review–supposedly the call on the field is overturned ONLY if there is indisputable visual evidence. What BS.)

  79. 17

    Following step-back’s quote and Lowly’s comment, maybe this is the time to take a crack at getting the Supremes or the CAFC to get rid of the “clear and convincing evidence” standard that the CAFC has read into 35 USC 282.

  80. 16

    smashmouth, given the amount of money at stake, it’s probably worth it for the generic to file a cert petition.

    That said, I don’t see a cert-worthy issue here. The district court and the CAFC both applied KSR. The main disagreement people seem to have is with the courts’ views of the facts.

    Good luck trying to convince the Supreme Court that a panel containing the 2 CAFC judges with chemistry Ph.D.’s screwed up the facts or failed to appreciate what a person of ordinary skill in stereochemistry would have thought. I doubt it’s coincidence that most of the Supreme Court cases addressing substantive patent law involve mechanical inventions.

    Maybe the en banc CAFC will have a different view of how the obviousness standard should have been applied, but that will also be a tough petition to write.

  81. 14

    The “issue” in this particular “appeal” was not whether the claimed composition was obvious, but rather whether the district court committed reversible error.

    “On the basis of this trial evidence, the district court found that a person of ordinary skill in this field would not reasonably have predicted that the dextrorotatory enantiomer would provide all of the antiplatelet activity and none of the adverse neurotoxicity. Clear error has not been shown in this finding, and in the conclusion of nonobviousness based thereon.”

  82. 13

    Luke,

    I’m with you too, including this panel reaching the right conclusion on these facts. (BTW, my undergraduate degree is in chemistry.) Also, there’s another factor being ignored here, namely “enablement” by the prior art. As this panel carefully noted (and as others on this posting have apparently ignored), the prior art didn’t “enable” the claimed stereoisomer in that there was no teaching of how to even separate the stereoisomers. In fact, the panel opinion noted very carefully how quite a bit of experimentation was required before a separation of the stereoisomers could be achieved. Another factor being ignored here is that what was claimed was a particular salt (the hydrogen sulfate/bisulfate salt) because of its tabletting ability (versus the hydrochloride salt which the far more common in the drug field). Face it folks, Judge Newman and the rest of this panel got it right this time.

  83. 12

    The reason the decision went the way it did was the evidence adduced. To the prejudiced, it is surprising how fact-based judicial decisions often are. Indeed if you happen to be a judge, you will exercise great care to see that your conclusions are supported by the evidence, otherwise you risk repeated and humiliating reversal.

    In this case the expert evidence is of great interest and the decision repays detailed reading, even if you do not agree with the outcome.

    I will go with Luke: enantiomers are often, but not always, obvious. There are no bright line rules, as the Supremes told us in KSR. Hindsight, of course, is always 20:20.

  84. 11

    Oh look, more non-chemists opining they know what makes a chemical compound obvious.

    Let’s look at the facts here.

    1. Previous enantiomeric separations of other members of the class of compounds had shown either *no* activity differences at all, or if there were differences, the activity differences were opposite to the toxicity differences and thus there was no reason to separate. Thus there is simply *no* incentive to try and separate the enantiomers – previous research has clearly shown this is unlikely to be profotable. Despite what some of the previous posters will tell you, who not only say it could be done, but it should be done (Do remember the literal meaning of obvious: ob via – in the way).

    2. One member of the class, however, after 7 years of playing around with separations, shows different behaviour. Not only doesn’t it follow the previously observed behaviour patterns – unexpected as that is, it also shows the extremely rare property of absolute stereoselectivity, which experts on both sides agreed was not predictable. However, some posters here would seem to say not only do know better than the judges, they know better than the experts in the court on both sides…

    Sure, enantiomers are often obvious given the racemate. Please observe the “often”. Not “always”. Just like homologs are not (or rather should not be) *always* obvious. Once again, a case that makes clear that obviousness is a question that involves factual questions. Those who want bright line rules along the lines of “Enantiomers are per se obvious” need to remember they are working in a profession that deals in facts – and facts are murky slippery things.

    Cheers, Luke

  85. 9

    yes the separation of an enantiomer from its racemate by tartaric acid is blatantly obvious, however, the caviat that very few of you seem to have noticed is that although the activity goes one way, I don’t even care which, the evidence at trial was that the toxicity went the other. This feature is disclosed in the patent (as opposed to the nonsense that was raised 15 years later in Forest as a blatant litigation precursor) and appears to hae swayed the panel.

    Plus it’s Newman, what dd you expect?

  86. 8

    I think Sanofi did get lucky here because another panel could reasonably have found Sanofi’s patent to be obvious.

    The facts in this case are mundane to say the least, for anyone who prosecutes biotech patents: novel product, isolated and identified by routine methods that are nearly always successful, is nevertheless non-obvious by virtue of the unexpectedly desirable properties of the claimed invention. Let me draw your attention to the last two words in the previous sentence because it’s a failure to responsibly address the **claimed** invention that leads to the issuance of crap in most cases.

  87. 7

    Wow. CAFC says an enantiomeric salt is both novel and non-obvious over Sanofi’s over earlier disclosure of the racemate that included statements that the claims includes the salts in enantiomeric form. And it appears the district court’s injunction is still in place. Nice to see that, even in the wake of KSR, eBay and the rest, a pharma patent can still be worth something.

    I especially like how this panel distinguished over KSR, noting that KSR dealt with a mechanical device in which the combination of familiar elements led to a predictable result, whereas here the separation of enantiomers led to an unpredicatable result.

    Waiting for Max to tell us how this doesn’t square with EPO practice, but the decision is pretty fact-dependent, and I don’t think it indicates that in the future all enantiomer patents will be held valid by the CAFC. It actually took a lot of work to separate the enantiomers. Sanofi was already millions of dollars into developing the racemate as the API for the product before it decided to separate the enantiomers and look at them separately, a fact the court viewed as indicating lack of motivation to try. And it helped that both sides’ experts agreed that “absolute stereoselectivity” – i.e. one enantiomer binds the receptor and gives only the desired result, and all the bad side effects are due to the other enantiomer – is rare and always unexpected.

    And Irving Kayton will be able to point to this case in support of his “don’t identify any embodiments as ‘preferred'” approach.

    Gideon, I’m surprised at your take on this – it means that there will continue to work on both sides of the industry for these kind of patents. Doesn’t that mean your cash register will be going “ka-ching”?

  88. 6

    Everyone knows that enantiomers can have entirely different characteristics. Its not a simple right handed glove left handed glove comparison. Its more of a left-handed molecule has one set of benign effects, one species of right-handed molecule causes liver disease and cancer and no beneficial effects, another species of right-handed molecule solves all the problems.

    Everything is simple in hindsight, that’s why Mooney and a stopped clock are right at least twice every day.

  89. 5

    Here’s some O-Chem 101 for non-chem folks.

    A “racemic” mixture has two mirror image molecules mixed together at a, usually, 1 to 1 ratio. Picture a large barrel of identical gloves – 1/2 are left handed and 1/2 are right handed, but otherwise they are identical.

    The mixture of the left hand glove and the right hand glove were in the art. Given.

    The process to separate the left from the right, resulting in a barrel of left only gloves and a barrel of right only gloves is well known in the art.

    This case decides:
    The right hand glove is patentable.

    Priceless.
    Yet one more example of Patents serving as rewards for Mega Corp.

  90. 4

    Even under the TSM test, this patent was obvious. Sanofi got pretty lucky–look who sat on the panel.

    I wonder if the generic mfr. will petition the Supremes.

  91. 3

    “The Federal Circuit disagreed with Apotex – finding “no error in the district court’s findings that, on the state of the prior art, a person of ordinary skill would not have had the expectation that separating the enantiomers would be likely to produce an isomer having absolute stereoselectivity as to both the favorable antiplatelet activity and the unfavorable neurotoxicity.” ”

    Who could have predicted that. A person of skill could easily have expected that separating the enantiomers would be likely to produce an isomer having stereoselectivuty – what a worthless pile of crap.

  92. 2

    When the court says “person with ordinary skill”, what exactly are they talking about? Someone who majored in chemistry in college? Someone with experience in the field? Or just some clueless jerk on the street?

    Their decision simply makes no sense to me. I’m a bright guy, but I know people who are smarter, and I am no chemist. Didn’t much like freshman chemistry, never took organic, never took chem lab. Nonetheless, I would expect that any drug would be likely to have stereoisomers with different properties. I know how important that is to biochemistry, I know about thalidomide, I know about naproxen sodium (pain killer/liver killer — better separate the two). Would I expect absolute stereo selectivity? I’d expect it enough to do the experiment, after all, other drugs work that way — it’s completely not novel if it happens.

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