Chemical Cases: Prima Facie Obviousness Requires “some Reason” for Modification

Takeda Chemical v. Alphapharm (Fed. Cir. 2007).

Alphapharm filed an ANDA with the FDA — hoping to begin making generic version of Takeda’s patented diabetes treatment ACTOS. ($1.7 b annual sales). The district court found the invention nonobvious, but Alphapharm asked the CAFC to review the case under the new standards of KSR v. Teleflex. On appeal, the CAFC affirmed.

Graham Primary Law: In the 1966 case of Graham v. John Deere, the Supreme Court set forth the primary methodology for determining obviousness. That methodology requires an examination of 1) the scope and content of the prior art; 2) differences between the prior art and the claims; 3) level of ordinary skill in the pertinent art; and 4) objective evidence of nonobviousness.  According the CAFC, KSR left the Graham formula intact, but added the provision that the test must be flexibly applied.

Although flexibility is required, one inflexible rule is that a prima facie obviousness rejection requires at least “some reason” that would have led a chemist to modify the prior art in a particular manner. Here, the court could find no reason for such a modification or that the modification would have been ‘obvious to try.’ – validity affirmed.

Genus-Species Unexpected Results: Judge Dyk in Concurrence indicated that two of the broader claims were likely invalid based on a rule of unexpected results for species:

In my view a species should be patentable over a genus claimed in the prior art only if unexpected results have been established.

 Dyk concurred with the validity finding because the “overbreadth” argument had been waived.


8 thoughts on “Chemical Cases: Prima Facie Obviousness Requires “some Reason” for Modification

  1. 8

    There may be some hope.

    Per the case, lack of motivation” :”it failed to show that there existed a reason, based on what was known at the time of the invention, to perform the chemical modifications necessary to achieve the claimed compounds.”

    The key here is what was known at the time of the invention. An examiner’s opinion exists at the time of the Office Action, not at the time of the invention. Unless the examiner provides written, document evidence that the motivation existed at the time of the invention, a prima facie case of obviousness would not be established.

  2. 7

    Dear Mr. Palazzolo,
    Are you the Petitioner, Anthony Palazzolo, about whom Justice Kennedy wrote this on June 28, 2001?

    Justice Kennedy delivered the opinion of the Court.
    Petitioner Anthony Palazzolo owns a waterfront parcel of land in the town of Westerly, Rhode Island. Almost all of the property is designated as coastal wetlands under Rhode Island law. After petitioner’s development proposals were rejected by respondent Rhode Island Coastal Resources Management Council (Council), he sued in state court, asserting the Council’s application of its wetlands regulations took the property without compensation in violation of the Takings Clause of the Fifth Amendment, binding upon the State through the Due Process Clause of the Fourteenth Amendment. Petitioner sought review in this Court, contending the Supreme Court of Rhode Island erred in rejecting his takings claim. We granted certiorari. 531 U.S. 923 (2000).

    Mr. Palazzolo,
    Are you an attorney? Are you patent attorney?
    In any case, what do you mean by your comment?:

    “ummmm … whose blog is this?”

    More about Supreme Court “Petitioner Anthony Palazzolo”
    link to
    A Property Rights Case Tests Wetland Curbs
    Supreme Court will hear Anthony Palazzolo’s lawsuit asserting that state of Rhode Island should compensate him for value he has lost by not being able to build on 18 acres of wetlands he owns in Westerly; Palazzolo will be represented by Pacific Legal Foundation, one of legal leaders of property rights movement; one issue in case is whether he bought land in 1959, before there were any restrictions, or in 1978, when they were already in place;
    February 17, 2001
    Supreme Court Roundup; Justices Press for Clarity in a Property Rights Dispute
    Supreme Court hears arguments on whether property owner who acquired land after wetlands regulations were in place is nevertheless entitled to claim compensation for ‘taking’ by the state; Rhode Island case involves Anthony Palazzolo’s waterfront property in Westerly, which he bought in late 1950’s and early 1960’s for $13,000 and now claims is worth more than $3 million that state should pay because he cannot build on most of site; …
    February 27, 2001

    link to
    link to

  3. 5

    The “lead compound” methodology actually derives from Yamanouchi v. Danbury, a Federal Circuit case written by Judge Newman. The case was not cited by the Court, deliberately I believe (it was all over the district court opinion). So the court is being more than a bit coy when it says it doesn’t understand what the parties mean by “lead compound.”

  4. 4

    Dear Sigh of Relief, I read the decision. thanks for urging me to do so. I got a surprise. Compound b didn’t work. The EPO would also have upheld claim 2. Judge Dyk would enjoy the EPO Agrevo Decision.

  5. 3

    A Patriotic Patently-O Post to celebrate AMERICA’s 231st INDEPENDENCE DAY:

    Focusing on three subjects dear to our American IP hearts, our
    (i) patent system,
    (ii) paper money, and
    (iii) premier position, I ask:

    Are Americans willing to cede our standing as the leading world power and step down, and trust world leadership to an other nation?, perhaps a socialist nation?, or a communist nation?, or a (neo)fascist nation?, or a totalitarian nation?

    Could America slip into second, or even third place? How would this even be possible?
    Here’s how — it would take a confluence/sequence of events, such as, for example, some of the following all-too-plausible tragedies:

    A) Our patent system, which gives America a clear innovative advantage, is being dismantled inch by inch and we could lose our world-wide competitive technological edge.

    B) The mighty American greenback, the world’s leading currency and life-blood of world commerce, has become a less-competitive store of value compared to the Euro.

    C) The “brain drain” has reversed, and we are losing our human capital advantage of trained and talented individuals to nations against which we are competing, while allowing increasing numbers of unskilled workers into our country.

    D) We are the world leader in energy consumption, while Germany is by far the advanced world leader in generating wind and solar energy, and France is the world leader in generating nuclear energy.

    E) Our military might is being stressed in the MidEast, and it could even get worse, and other nations could close the military technology gap.

    F) Our financial, commerce, transportation and other systems are dangerously subject to the vageries of the vulnerable Internet.

    F) Our cities are targets for terroists-sponsored and state-sponsored wmd attacks. New York and Washington could be struck, for example, by dirty nukes that render them uninhabitable for hundreds of years.

    “On July 4, 1776, we claimed our independence from Britain and Democracy was born. Every day thousands leave their homeland to come to the ‘land of the free and the home of the brave’ so they can begin their American Dream.” (Quoted from a U.S. President’s July 4th speech).

    Certain European sentiment has been overtly and covertly advancing anti-American patent system trash aimed toward neutering our system, for example:
    (i) Reducing the ability to enjoin an infringer of a valid patent;
    (ii) Increasing the number of ways to invalidate a patent;
    (iii) Limiting the damages award so that it pays an infringer to refuse to license;
    (iv) Limiting the scope of, and possible ways an inventor can patent his invention; and,
    (v) Vilifying self-employed American inventors and advocating sending “vexatious litigants … asserting claims found to be invalid” to prison jail under some circumstances if their litigation against an infringer fails.

    Some shamelessly stubborn oaf keeps trying to take advantage of American Internet forums to drag our pro-inventor patent system down to the feeble European level. No matter the essential truths which he doesn’t read or know, the half-cocked oaf incessantly promotes STERILIZING The AMERICAN innovative competitive intellectual property ADVANTAGE that was described in a comment that was written anonymously, but obviously written by one of Patently-O’s most insightful and brilliant American patriot contributors.
    [A+]: — The following comment, perhaps the best Patently-O comment I’ve ever read, was posted on Jun 26, 2007 at 07:33 AM on this thread-link — :
    link to

    Here are excerpts from this excellent, extremely judicious and well written A+ post:

    “ … The bottom line is that the majority of European law is based on a far more socialist leaning basis than we’ve adopted in the US … different in the manner in which individual contribution to the common good is measured.

    “In the area of patent law, especially patent enforcement, Europe is damn near the least cost effective playground in the world …

    “The bottom line is Europe doesn’t enjoy the benefit of independent inventor’s contribution to innovation to the extent we do in the US because they don’t compensate for it. We do, because we compensate for it. Being an independent inventor is, financially, among the highest risk professions. …


    Despite this optimistic view of our patent system, FORE WARNED IS FORE ARMED:
    A most problematic picture has been emerging: Owing in large part to the greed/growth based agenda of Organized Big Business, OBB (which could turn out to be worse than organized crime syndicates), our American patent system is being weakened from within by all three branches of our government, via proposed Congressional patent-weakening reform, Supreme Court decisions based on Constitutionally corrupt patent statutes, and by the USPTO succumbing to public pressures cleverly created by OBB.

    Our Court of Appeals for the Federal Circuit, the CAFC, has been resisting the corruption of our patent system, but it is an uphill battle because of:
    (i) OBB’s steady broad-based lobbying efforts,
    (ii) Conjured up fairytale troll-talk,
    (iii) Overt and covert anti-patent attacks continuously surfacing.
    These anti-patent efforts are taking their toll inch by inch. OBB wants to $uck blood money from flattening global markets. Maybe that’s put too crass, but you get point.

    My recent concern about our patent system brought back my gloomy concern from the 90s regarding America’s leadership position after certain events occurred, events comprising:
    (i) winning the cold war against the Soviet Union,
    (ii) the dismantling of the Berlin Wall, and
    (iii) Germany Unification.

    My concern for America’s world leadership position grew dire in the mid 90’s when I caught part of William F. Buckley Jr.’s PBS Firing Line talk show with guests that included Henry Kissinger (despite my search efforts, I have never been able to find a transcript of that show). During the show’s discussion, a surprise question arose:

    “HOW LONG WILL THE UNITED STATES REMAIN THE ONLY, OR THE LEADING, SUPERPOWER?” The first responses were, perhaps 50 years or longer? But the ensuing discussion wound up with the alarming consensus that OUR LEADERSHIP COULD BE LOST IN AS LITTLE AS TEN YEARS. Democracy is on a slippery slope.

    Mid-stream Americans still take for granted our nation’s leadership position. However, the gravity of that mid-90s Firing Line show’s revelation shattered any notion I had that America’s leadership is necessarily permanent. AMERICA’S LEADERSHIP IS NOT PERMANENT — it hangs by a thread.

    As events over the past two administrations have demonstrated, our government is not up to doing its job. Not only have all three branches been infiltrated and tainted by OBB’s greed/growth world-is-growing flat agenda, but our two-party political system seems to be unraveling. We have no statesmen strong enough to pull us out of what appears to be a deadly political tailspin. (Perhaps an independent party candidate could win in 2008, and that could shed some hope).

    Prior to my dire national concern, I spearheaded a pragmatic proposal to Treasury in the mid-80s, to start an international American currency databank based on American-owned proprietary technology to bolster the American greenback. Working with the founding partner of a large powerful prestigious Washington-based lobbying law firm in the mid-90s, my proposal to Treasury was based on patents that had issued — my motives were personal profit as well as patriotic pride. The proposal was to issue new, technologically secure high-denomination banknotes with unique bar-coded numbers printed simultaneously with the Arabic serial numbers using modified computer-controlled numbering wheels on the intaglio currency presses.

    With bar-codes and a databank money could be tracked to detect laundering and terrorist transfers and provide leads to help authorities locate bank robbers, kidnappers and counterfeiting rings. Criminal activity involving cash could not escape extremely cost-effective certain detection by computer programs. An American currency databank would rival the extreme unique value of the FBI’s Integrated Automated Fingerprint Identification System (IAFIS).

    Congressmen and their staff to whom we pitched our proposal responded enthusiastically and supported our efforts, but the Bureau of Engraving and Printing defended its forensic printing techniques as being more than adequate. We got nowhere with any executive branch agency, and the VP, who supposedly invented the internet and was in charge of incorporating benefits of new technology into government applications, was out somewhere raising money, and the President had his head under his desk.

    While the U.S. struggles today to maintain the integrity of our $100 Franklins against state-sponsored “supernote” counterfeiting, the EU is floating 500 Euros worldwide. To our chagrin, “Euroization” has been replacing “Dollarization” (please see footnote below).

    IN CLOSING — We should all be scared sleepless of these tragedies:
    (i) Our weakening patent system;
    (ii) our greenbacks losing their world-wide appeal;
    (iii) our growing catastrophic loss due to the reverse brain drain;
    (iv) our heads in the sand when it comes to vital energy innovation;
    (v) our increasingly stressed military might and lessening military technological adavantage;
    (vi) our extreme dependance on the vulnerable Internet; and
    (vii) our cities being targeted for simultaenous mass destruction.

    All this is why I ask:
    Are Americans willing to cede our prestigious premier position, step down and trust world leadership to some other nation?, perhaps to a socialist nation?, or a communist nation?, or a (neo)fascist nation?, or a totalitarian nation?

    Our government is hopelessly polarized, and dangerously short-sighted to boot — it is not protecting our long-term interests. We in the intellectual property community are smarter than your average bear. The buck stops here, in our IP laps. If not here then where? If we, some of the brightest, best and most affluent our nation has to offer, sit by and do nothing, we will be ashamed of ourselves, to say the least, when we wake up one day as citizens in a second-rate nation.

    DON’T LET OUR PATENT SYSTEM BE DENIGRATED — we must start reversing that trend. Celebrate Independence Day and think, think of things to help preserve our country’s leadership before we lose it.

    In the words of one of our most unique and endearing American patriots, Yogi Berra:
    It ain’t over till it’s over your head.

    Until 2002 when the actual physical Euro currency was first floated, the United States had been the unchallenged global leader in the exportation of its currency, a function of our “seigniorage” business, issuing currency. Today, it is estimated there are twice as many Euros floating and/or being hoarded as a store of value in third world nations as U.S. dollars (the equivalent of almost one trillion U.S. dollars is floating in Euro banknotes).

    Selling U.S. $100 bills abroad is our most prestigious and profitable national business: the profit in producing a $100 bill is about $99.96 (a 249,900% mark-up, not counting the imputed reoccurring annual interest on the float). One reason the Euro is taking over our seigniorage business is that the EU produces 500 and 200 Euro notes, which makes it about 6.75 times more compact that our US$100 bill given the weakening exchange rate (the rate went from $0.85 in June 2001, when the Euro was only an “accounting currency,” to favoring the Euro to the tune of $1.35 last month, June 2007).

    Permission to copy encouraged and hereby granted. No rights reserved. Please credit:

  6. 2

    MaxDrei, read the case please. What in this case would be considered the “closest prior art” was a compound that had a methyl group (-CH3) at one position on a ring. The active ingredient in Takeda’s drug had an ethyl group (-CH2CH3) one position over on the ring. The prior art taught that the “closest prior art” compound would be a lousy starting point for making a drug that did what Takeda’s drug did. Said the CAFC, Since one wouldn’t even start from that “closest prior art” compound, let alone modify it to get to Takeda’s compound, there was no obviousness. Moreover, objectively Takeda’s compound was better than the “closest prior art” compound for the job that Takeda used it for – it was significantly less toxic, which I suspect even in the EPO would probably have qualified as “inventive step”.

    The CAFC got this one right – although the “starting point” argument is unusual, but apparently that’s how the parties briefed this case. If after reading the case you think that the EPO would have decided it differently, please let us know.

  7. 1

    US law requires disclosure of the best mode, EPO not. EPO thinks that “a reason” good enough to render a mere alternative obvious is that what companies routinely, ploddingly, uninventively do is modifications that do the job equally well. Mostly, variations are not out of reach and not inventive to adopt. Does the US skilled addressee lack “a reason” to try an alternative because he knows that they will all perform worse than the “best mode”?

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