AstraZeneca v Apotex: Affirmance of a Preliminary Injunction

By Jason Rantanen

AstraZeneca LP v. Apotex, Inc. (Fed. Cir. 2010)
Panel: Rader, Bryson (dissenting in part), Linn (majority author),

Contrary to popular opinion, it's still possible to obtain a preliminary injunction in a patent case – it's just very difficult.  Astrazeneca v. Apotex provides an example of an affirmed preliminary injunction, and is significant for that reason alone.  It also raises some interesting inducement issues relating to intent that I'll discuss in a separate post.

Background
This case revolved around AstraZeneca's budesonide inhalation suspension drug product, which consists of a vial containing a single dose of budesonide suspended in a sterile liquid.  The drug is administered by squeezing the entire contents of the vial into a jet neubulizer, then inhaling the resulting mist through a mask attached to the nebulizer.  Because budesonide is an inhaled corticosteroid, the FDA requires that the label include a warning instructing patients to "titrate down" to the lowest effective dose of the medication to avoid any adverse effects from excessive use of the medication. 

The two patents at issue, Nos. 6,598,603 and 6,899,099, both contain method claims covering the once-daily use of the nebulized dose of a budesonide composition and product claims covering AstraZeneca's drug product kit.

Apotex sought approval to market a generic version of AstraZeneca's drug product.  As an ANDA applicant, it was well aware of AstraZeneca's patents, and sought to avoid the once-daily method claims by removing any mention of once-daily dosing from its labels.  While it succeeded in part, the FDA nevertheless required Apotex to keep the titration warning language in the generic product's label.

During the preliminary injunction proceedings, Apotex raised two principal arguments in response to the method claims.  First, it contended that they were anticipated; second, it contended that its distribution of the generic version of the drug would not induce infringement of AstraZeneca's method claims.  The district court rejected Apotex's arguments, and granted a preliminary injunction enjoining Apotex from marketing its product.

Note: The district court agreed with Apotex that the kit claims were invalid.  On appeal, the panel affirmed that determination. 

Anticipation
Apotex's first anticipation argument, involving a prior art patent, turned on a question of claim construction: whether the term "budesonide composition" encompassed budesonide encapsulated in liposomes (the '603 patent teaches dispersing budesonide in a solvent, either as a solution or a suspension that may include liposomes as an excipient).  The majority agreed with AstraZeneca's position, focusing on the discussion contained within the specification and buttressing its conclusions with extrinsic evidence (in this case, expert testimony).  Judge Bryson, dissenting on this point, reached the opposite conclusion: the claim term is not limited to budesonide directly dispresed in solvent, and thus the method claims are anticipated.

Apotex's also argued that a prior art British advertisement for AstraZeneca's product describing it as a twice-daily product anticipated the patents.  The majority again agreed with AstraZeneca that this reference did not anticipate the once-daily method claims, both because it did not disclose once daily dosing and because it was not enabled with respect to that type of dosing.  (Obviousness was apparently not in dispute, as at the time of the earlier reference no one recognized that the product could be administered once per day and still be effective).  Judge Bryson again disagreed, reading the prior art advertisement to suggest the administration of the drug once a day.

Inducement of Infringement
In challenging the district court's finding of inducement of infringement, Apotex focused on the subject of intent, arguing that its instructions did not demonstrate intent to cause the users of its product to engage in once-daily dosing and that it lacked specific intent to cause infringement of Apotex's patent.  The Federal Circuit rejected these arguments, affirming the district court's conclusion that the downward-titration instructions would necessarily result in some users engaging in once-daily dosing and noting that Apotex was well aware of the infringement problems raised by once-daily dosing, yet chose to proceed nonetheless.

Preliminary Injunction "Substantial Question of Invalidity" Standard
Although not playing a major role in the ultimate outcome of this appeal, the court's articulation of the "likelihood of success" standard, along with the subsidiary "substantial question of invalidity" element, is noteworthy given the divergent views on this subject, such as those expressed by Judges Newman and Gajarsa in Abbott Laboratories v. Sandoz, 544 F.3d 1341 (Fed. Cir. 2008).  AstraZeneca v. Apotex follows the approach of requiring a seemingly high threshold for patentees/low threshold for defendants on this issue:

For a patentee to establish that it is likely to succeed on the merits, it “must demonstrate that it will likely prove infringement of one or more claims of the patents-in-suit, and that at least one of those same allegedly infringed claims will also likely withstand the validity challenges presented by the accused infringer.” Ama-zon.com, 239 F.3d at 1351. When reviewing the grant of a preliminary injunction, this court “views the matter in light of the burdens and presumptions that will inhere at trial.” Titan Tire Corp., 566 F.3d at 1376 (citation omitted). A preliminary injunction should not issue if an alleged infringer raises a substantial question regarding either infringement or validity, i.e., the alleged infringer asserts an infringement or invalidity defense that the patentee has not shown lacks substantial merit. Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1364 (Fed. Cir. 1997).

62 thoughts on “AstraZeneca v Apotex: Affirmance of a Preliminary Injunction

  1. what happens if the sequence on your computer-readable medium is found in someone’s genome?

    Seriously IANAE? Ya even havta ask? Damm, I thought I done taught ya better than that. Quite disappointing when someone the likes of Alun dismantles your position so easily.

    Yet ya persist in traveling to middle earth where the Nazguls eat your head.

  2. Because the binary code didn’t exist in nature, but was created by man.

    But you don’t know in advance that every claimed DNA sequence existed in nature. What if the sequence was first created in a lab? Still non-statutory? Non-statutory subject to someone later finding that sequence in nature?

    Also, considering that quaternary data is equivalent to twice as many bits of binary data, what happens if the sequence on your computer-readable medium is found in someone’s genome?

  3. “Based on the law alone, without regard to policy, explain to me again why a computer-readable medium recording an unspecified binary code having a claimed utility is statutory, whereas an enzyme-readable medium recording a specified quaternary code whose utility is inherent in the structure of the reader is non-statutory.”

    Because the binary code didn’t exist in nature, but was created by man.

    Ask me a hard one.

  4. “I didn’t post the BPAI decision btw.

    Posted by: 6 | Nov 05, 2010 at 12:00 PM”

    cf

    “http://www.uspto.gov/ip/boards/bpai/decisions/inform/fd09004693.pdf

    LUUUULLLLLZZZZZZ”

    LULZ indeed. I lulzed heartily after reading this decision. The grounds for affirming made my day. Informative opinion indeed lol.

    Imo 112 2nd, is it an apparatus, product, or a method in the claim? It seems to be an apparatus being distinguished in terms of method steps, as all its parts are doing things right now (aka method steps as opposed to some function).

    Posted by: 6 | Nov 05, 2010 at 01:08 AM

    W

    T

    F

    Anyone who knows me knows I routinely play around with my words intentionally. If they don’t like it, then I’m at the wrong firm anyway.

    firm? You will never fiind the right firm – you are in the wrong industry.

  5. “Anyone who knows me knows I routinely play around with my words intentionally. If they don’t like it, then I’m at the wrong firm anyway.”

    Good luck finding the right firm.

    Lulz

  6. IANAE:

    OK. So we are looping. For Beauregard claims if the issue is specificity, then we can have a good discussion. There is a long history in patent law of discussion how specific an invention needs to be claimed. So, if this is your only issue, I think we are making progress.

    >>yet you rely on it as an authority as if it’s >>settled law,
    Don’t be ridiculous. The court took the patent out and now it is on appeal. The issue arises from the lower court ruling.
    You should be able to state what differences you have with the lower court other than a blanket I don’t agree with it. Focus and try to come up with dispositive issues you have with the court’s holding.

  7. I would suggest that you focus on what are the issues for whether a judicial exception should apply to an isolated gene.

    Well, it would be an exception, and I can’t think of any exceptions that might apply, so I don’t think there are any issues. I think it’s clearly statutory.

    Can you tell me what the issues are? Focus.

    I don’t think there are any issues. You can’t focus enough to make up your mind about whether there are any issues. So how’s about we agree that isolated genes are statutory as molecules based on the general rule in 101 unless and until you can figure out which exception applies.

  8. We were trying to narrow the issues.

    Yes. I’m trying to narrow the issues in a discussion with someone who likes Beauregard claims and doesn’t like gene claims (but has trouble saying so) by suggesting that the level of specificity of the claimed subject matter isn’t the issue.

    Both are claims to readable code, essentially. So why do you have such a hard time making up your mind about one when you’re so certain about the other? Not for policy reasons, I hope.

    Goodness. The isolated gene was taken out by a judicial excpetion and you bring in that it is more specific than a Bearegard claim? Nonsensical.

    It’s funny, really. You’re very careful not to say you agree with that decision, and yet you rely on it as an authority as if it’s settled law, when it’s still on appeal and far from clearly correct.

  9. I would suggest that you focus on what are the issues for whether a judicial exception should apply to an isolated gene.

    Can you tell me what the issues are? Focus.

  10. >>tangled web you weave

    So, let me get this straight. We were trying to narrow the issues. You then say that your Beauregard statements were to illustrate that the isolated gene is more particularly claimed. OK. So, you switched completely the issue and hide the issue. OK. Good start.

    You seem to be arguing it’s not fair. You got the Bearegard claims and we didn’t get the isolated gene claims!! Wah! Well, ok, if that is the way you feel, then go and have a good cry. If you’re intellect is offended, then try to figure out what the issues are and narrow them down.

    Goodness. The isolated gene was taken out by a judicial excpetion and you bring in that it is more specific than a Bearegard claim? Nonsensical.

  11. If that is the only thing that troubles you about Bearegard claims, then you are very nearly in our camp.

    That’s not the issue, it’s simply an example of how genes are claimed much more narrowly and with much more specificity.

    Isolated genes are statutory unless a judicial exception applies. I have not completely formed my opinion on whether one should or should not apply.

    Very amusing. Let me know when you’ve thought of a judicial exception that doesn’t also apply to Beauregard claims, and we’ll have a nice conversation then.

    What a tangled web you weave.

  12. “I can’t wait til you provide that “explanation” to a partner who calls you out on your ignorance. It’ll be a short trip to the unemployment line from there.”

    Anyone who knows me knows I routinely play around with my words intentionally. If they don’t like it, then I’m at the wrong firm anyway.

  13. >>The desired utility is specified.

    The actual sequence of ones and zeros do not need to be specified. If that is the only thing that troubles you about Bearegard claims, then you are very nearly in our camp.

    Isolated genes are statutory unless a judicial exception applies. I have not completely formed my opinion on whether one should or should not apply. You need to find someone else to fight about this one.

  14. “We disagree here. It is specified in functional terms.”

    But it could be anything right? 1010101 could be it for every B claim ever pretty much?

    I posted in response to your other things you said but it ate them and I’m not retyping.

    I didn’t post the BPAI decision btw.

  15. Just as Liberals seem to have a curious aversion to having a conversation on mutually accepted terms.

    See Gene Quinn’s website for literally hundreds of examples.

  16. “I know what it ‘means’ I simply used it differently here.”

    I can’t wait til you provide that “explanation” to a partner who calls you out on your ignorance. It’ll be a short trip to the unemployment line from there.

  17. Anon, you may have missed this, but I’m inviting him to play in his own web.

    Conservatives always seem to have a curious aversion to having conversations on their own terms.

  18. It is specified in functional terms.

    The desired utility is specified. The actual sequence of ones and zeros is not, and unlike genes it would be effectively impossible to determine from the sequence of ones and zeros alone whether the claim is infringed.

    I’ve never said I agree with the lower court

    You haven’t exactly been openly critical of the lower court.

    In your humble opinion, are isolated genes statutory or not? Your answer is important – it will help narrow the issues for discussion.

  19. Right. A fair treatment of the law would be equal to everybody. In other words, it would allow Beauregard claims…

    So what are the issues that we need to discuss if we’re going to resolve this?

    Come into my web so we can discuss this, says the spider to the fly.

  20. >>unspecified binary code

    We disagree here. It is specified in functional terms.

    >> is non-statutory

    I’ve never said I agree with the lower court despite you at least 5 times telling me or assuming that I do.

  21. So, you see you already started down the road to illustrate that you are not interested in a discussion that narrows the issues.

    That’s exactly it. Completely uninterested. Despite all those narrow issues I’ve been discussing at considerable length, only to see you change the subject whenever you didn’t get your way.

    Tell you what, I’ll give you another chance. Statutory subject matter is one of the issues, right?

    Based on the law alone, without regard to policy, explain to me again why a computer-readable medium recording an unspecified binary code having a claimed utility is statutory, whereas an enzyme-readable medium recording a specified quaternary code whose utility is inherent in the structure of the reader is non-statutory.

    You may assume that both the medium and whatever is doing the reading are prior art in both cases.

  22. So, you see you already started down the road to illustrate that you are not interested in a discussion that narrows the issues.

  23. >>No, it’s not. I’m sure you’ve come up with far >>better.

    That certainly moved the ball forward–not.

  24. Benson is probably the best example of an outcome driven decision.

    No, it’s not. I’m sure you’ve come up with far better.

  25. IANAE: the result is not what bothers me. It is the reasoning to get there. Benson is probably the best example of an outcome driven decision.

  26. The people to whom I speak are being intellectually dishonest and not treating the law fairly.

    Right. A fair treatment of the law would be equal to everybody. In other words, it would allow Beauregard claims and not allow isolated gene claims. Because that’s totally an honest and dispassionate reading of the law unencumbered by any policy considerations (e.g. computers are the future, gene research is an abomination unto the lord), and no reasonable disagreement will be tolerated.

    Nor are they trying to narrow down the disagree to an issue that can be discussed.

    But you are, right? So what are the issues that we need to discuss if we’re going to resolve this?

  27. IANAE: why?

    The people to whom I speak are being intellectually dishonest and not treating the law fairly. Nor are they trying to narrow down the disagree to an issue that can be discussed. Rather they are mispresenting the law and intentionally trying to muddle the issues.

  28. All, in my opinion, shameful people that destroy the foundation of patent law to achieve policy goals.

    Why can’t you just say “All people with whom I disagree” like regular people do?

  29. You see 6, MM’s statements are as repugnant to me as suggesting raping another person. The law should not be raped.

  30. You see, 6, you think this is some kind of joke to use the law to achieve whatever outcome you want. That is the Lemley’s of the world.

    But, there are some of us that respect the law and respect the phrase equal under the law and know that if the law is perverted by policy that there is no law.

    Too bad for you that you don’t feel the power of truth and wonder in the law, but rather only the slime and shameless exploitation of the law.

    Shame on you and MM.

  31. You see 6, I am not alone. I know I stand with J. Rich, J. Newman, Chisum.

    You stand with J. Moore, Lemley, and Richard Stern. All, in my opinion, shameful people that destroy the foundation of patent law to achieve policy goals.

    I would have loved to watch a panel with J. Moore and J. Rich. Moore would have been b$tch slapped until she realized that there is nothing she has to say worth the energy of moving her jaw.

  32. whats going on with Bryson’s off target statements on anticipation? Obviousness should have been raised, but there’s no anticipation.
    102 is a black and white issue.

  33. But you will note the date on his paper 6. I form my own opinions on these matters and write on them.

  34. >>but Chisum is a Patent God who knows his shtt

    He absolutely is. 6, you should read Chisum often. He and Newman understand patent law. If only Judge Rich were still here to bat down the mob.

  35. 6,

    I fail to see the relevance of your posted BPAI decision of more than a year ago. Clearly stamped “Informative” and clearly in error with its line of “Appellants have the burden on appeal to the Board to demonstrate error in the Examiner’s position.“, what does a crrpily argued appeal have anything to do with this thread?

    And no dis-respect intended to NWPA, but Chisum is a Patent God who knows his shtt. Ya might try learnin somethin from him instead of hangin out at Grok and Slash and reinforcin your hatred of the patent system.

  36. Best line of the thread:

    Wow. This sounds like a good case to not read.

    And Iza not being Cy-nical abouts it.

    No I know what it “means” I simply used it differently here. If you don’t like it I don’t really care.

    Shockers – like we haven’t seen this attitude a million times before – the universal comeback from one whose ankle is wrapped in the stirrup and whose head is being pounded by hooves.

    Here’s an observation 6 – if ya ever do make it past your “trial” LSAT test attempts, ya gonna havta learn to care about using language correctly and suspend your “differently used” habits.

  37. “http://www.uspto.gov/ip/boards/bpai/decisions/inform/fd09004693.pdf

    LUUUULLLLLZZZZZZ”

    LULZ indeed. I lulzed heartily after reading this decision. The grounds for affirming made my day. Informative opinion indeed lol.

    Imo 112 2nd, is it an apparatus, product, or a method in the claim? It seems to be an apparatus being distinguished in terms of method steps, as all its parts are doing things right now (aka method steps as opposed to some function).

  38. It begs the questions: Is NWPA Chisum? Or is NWPA simply a Chisum fanboi?

    Someone doesn’t know what “begs the question” means.

  39. The dosage forms here could not be divided. They are capsules that go in a nebulizer.
    On the FDA is the inducer argument, the court agreed with AZ that if the only approved labeling would induce infringement the generic should stay off the market until the patents expire.
    On the substantial non-infringing use issue, maybe the current dozing guidelines make the higher dose non-substantial?

    I wrote up the contrast between the product labeling and kit labeling:
    http://Www.PharmaPatentsBlog.com

  40. “Because the district court did not abuse its discretion by granting the preliminary injunction and did not err in determining that the kit claims are invalid, this court affirms.”

    Lulz this inj. is the biggest abuse of discretion I’ve seen in a long time.

    He ll even I don’t abuse my discretion this bad. This judge put his discretion in a battered discretion home I think.

    “continuing regimen at a frequency of not more than once per day.””

    That’s the thing which is at issue. It’s a negative limitation limiting the claim in the same way that “continuing regimen at a frequency and not going to the moon” limits the claim. Implicit information in the prior art is implicit.

    “The district court concluded that at the time of its publication the Thorax advertisement did not enable once-daily dosing,”

    Lulz, I wonder if it enabled “not going to the moon” or not? I wonder if it enabled “not punching a rtarded judge in the face” or not? All interesting questions.

    ““the maintenance dosage should be the lowest dosage which keeps the patient symptom-free.””

    Sounds anticipatory to me. Now whether or not anticipatory language invalidates the claim is a question for a court to mess up.

    A real pity that Rader didn’t have anything to say on the subject. I also can’t find Linn discussing this anywhere in this voluminous opinion.

  41. “It all makes sense, as long as you don’t think too hard.”

    It all makes sense that it is nonsense. I believe I remember this case now. How the DC would have given them a prelim inj. is beyond me. They should appeal to the Fed. Circ.

  42. By analogy, suppose the doctor says take 25 milligrams a day. The pill is 25 milligrams. What does one expect the patient to do?

    Ned, you’ve never seen or heard of a prescription for “half a tablet, twice daily”?

  43. “by the time you get served with the infringement action it should be apparent whether you’ve taken a second dose that day.”

    What if I took it in secrit? I think that’s the answer in this case. Everyone should simply make it clear that there is no clear or convincing evidence that they did not take a 2nd dose in a given day or whatever.

  44. By analogy, suppose the doctor says take 25 milligrams a day. The pill is 25 milligrams. What does one expect the patient to do?

    You could always cut the Gordian knot and crush the pill to powder.

    If the available dosages don’t permit a non-infringing use, then clearly any sale of that drug is an inducement unless one makes a non-infringing dosage available. If the FDA requires that instructions to infringe accompany the drug, the generic has a problem.

    However, that raises two important issues in this case:

    1. The drugs do have a substantial non-infringing use, namely the prior art use of more frequent dosing.

    2. The prior art had the same dosage forms and came with the same instructions regarding the dosage. Some prior art users would have been able to reduce their dosage only by taking the drug once daily.

  45. I brieftly scanned the case, so if I get this wrong, let me know.

    The problem was in the minimum dosage levels for sustaining use. The label (I am not sure about this) said to make it 0.25, which was the dosage needed for once-a-day use. Had the label said 0.125, it would take 2 doses to get to 0.25, the mininum effective daily dose.

    The defendant knew that the 0.25 dosage level would lead to one-a-day use. That was the problem.

    By analogy, suppose the doctor says take 25 milligrams a day. The pill is 25 milligrams. What does one expect the patient to do?

  46. So I infringe if I take a single dose, regardless of what happens afterwards?

    Only if it’s your first one that day. Or maybe only if you forget to take your second dose. You might also induce infringement by encouraging someone else who has taken a first dose to do something dangerous like rock climbing or bungee jumping prior to taking the second dose. Anyway, by the time you get served with the infringement action it should be apparent whether you’ve taken a second dose that day.

    There is an intent requirement for anticipation?

    Of course there is. That’s why Apotex’s instructions inevitably result in direct infringement, whereas the same instructions in the prior art advertisement don’t inevitably result in anticipation.

    It all makes sense, as long as you don’t think too hard.

  47. Here’s another question: I inhale some of this drug. Am I direct infringer because I took a single dose? Or do I only become one if get hit by a car afterward and am unable to take the second dose?

    You infringe in either case

    So I infringe if I take a single dose, regardless of what happens afterwards? Then surely the claims are anticipated because every one who took two doses took one dose first.

    had either of those things happened before Astra’s date, you would not have anticipated because you never would have thought of doing what you inevitably did

    There is an intent requirement for anticipation?

  48. The Federal Circuit rejected these arguments, affirming the district court’s conclusion that the downward-titration instructions would necessarily result in some users engaging in once-daily dosing

    Sounds like the FDA is doing the inducing here, not Apotex.

    And how is it that the British advertisement plus the FDA requirement didn’t “necessarily” cause users in the US to engage in once-daily dosing prior to the filing date, or at least render such a use obvious?

  49. What was their non-frivolous argument for the validity of those claims in light of the settled law?

    Presumably that the claims are issued and presumed valid, and it’s not up to them to raise arguments for validity.

    Here’s another question: I inhale some of this drug. Am I direct infringer because I took a single dose? Or do I only become one if get hit by a car afterward and am unable to take the second dose?

    You infringe in either case, but had either of those things happened before Astra’s date, you would not have anticipated because you never would have thought of doing what you inevitably did.

    Honestly, this isn’t complicated. Try to keep up.

  50. I would like to know why AstraZeneca was not sanctioned for asserting the kit claims.

    What was their non-frivolous argument for the validity of those claims in light of the settled law?

    Here’s another question: I inhale some of this drug. Am I direct infringer because I took a single dose? Or do I only become one if get hit by a car afterward and am unable to take the second dose?

    Obviousness was apparently not in dispute, as at the time of the earlier reference no one recognized that the product could be administered once per day and still be effective

    So if I take a single dose and it’s not effective, I don’t infringe?

    no one recognized that the product could be administered once per day

    When you look at this way, it’s a rather ridiculous proposition. Of course it could be administered once a day and everyone knew that.

    If there was something new about the product, then the new product should have been claimed. Otherwise this drug should have gone generic.

  51. Why not? Because it means that you can validly patent something that other people are already doing, and then sue them for direct literal infringement.

  52. We see one of the same problems here that we saw in the King v. Eon case, and to a lesser extent in Prometheus. The very existence (or awareness) of the patent in suit converts non-anticipatory prior art conduct into inherent infringement. And again, the relevant conduct is what happens in the mind of the “infringer” when he reads a label.

    This can’t possibly be the right result.

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