Editorial: The Orange Book Should Include Process Patents or Be Eliminated

By Aaron Barkoff

Pharmaceutical-related patents are allowed in the FDA’s Orange Book only if they’re “composition” or “method of use” patents.  Such patents may cover the drug compound, specific formulations of the drug, or methods of treating certain diseases by administering the drug.  But “process patents,” which cover methods for making (chemically synthesizing) the drug compound, are not allowed to be listed in the Orange Book.  This inconsistency creates several problems for drug companies.

In ordinary circumstances, a patent owner trying to enforce its patent must first get the competitor’s product, look at it and test it, determine that it’s covered by the patent, and then file a lawsuit.  In most pharmaceutical patent cases, however, the patent owner need not bother with that.  Instead, if an innovator drug company lists its patent in the Orange Book, a generic drug company is required by law to notify the patent owner that it is making (and plans to sell) a drug that arguably infringes the patent.  Once notified, the patent owner can file a lawsuit for patent infringement.  But notice of possible infringement is required only with respect to patents that are listed in the Orange Book.  A patent might not be listed for in the Orange Book because either (a) it’s a process patent; or (b) the patent owner simply forgot to ask the FDA to include it in the Orange Book.

For generic drug companies, the Orange Book provides notice that there are patents out there covering FDA-approved drugs.  This relieves the generic drug company’s burden of searching for patents before it invests in research to develop a generic drug product.  But patent searching isn’t too difficult nowadays, and generic companies have to do it anyway because not all patents of concern are listed in the Orange Book.

For innovator drug companies, the Orange Book provides more valuable benefits.  First, the Orange Book relieves the innovator’s burden of monitoring the marketplace for new generic drugs that infringe its patents.  As long as an innovator drug company gets its patent listed in the Orange Book, a generic drug company that desires to make its own version of the drug must, under law, provide notice of possible infringement to the innovator.  Upon receiving notice, the innovator is free to file for patent infringement–without having to see the generic product or conduct expensive chemical testing on it.  Second (and probably more importantly to the innovator drug companies), the filing of a lawsuit based on a patent listed in the Orange Book automatically invokes a 30-month stay before the generic drug company can sell its drug.

But why can’t any patent relating to an FDA-approved drug be listed in the Orange Book?  The answer must be in some sort of bargain struck by lobbyists.  After all, the reasons for the Orange Book’s existence apply as well or better when it comes to process patents.  For example, to enforce its process patents, an innovator drug company has to monitor the marketplace, obtain a sample of the competitor’s product, test it, and establish a “good faith basis” for filing a patent infringement lawsuit.  In other words, the innovator drug company has to gather some evidence (usually the results of chemical testing) that the generic drug company uses the patented process to make the drug.  It is difficult and expensive to gather such evidence.  In fact, in most cases it would probably be easier to find chemical evidence that a generic drug company infringes a compound or formulation patent, yet because compound and formulation patents may be listed in the Orange book, such monitoring and evidence isn’t required.

Furthermore, owners of process patents must continue to monitor the marketplace even after they win in litigation.  Suppose an innovator drug company monitors the market, tests a new generic drug, suspects infringement of its process patent, files a lawsuit, and wins.  The generic drug company must then stop selling its drug.  However, the generic drug company is free to purchase API made differently, from a different source perhaps, and amend its drug application with the FDA.  The innovator drug company that already proved infringement won’t be given notice, and therefore must continue to monitor the market and test all new drugs for infringement of its process patents.  Such continuous monitoring isn’t necessary for owners of composition or method of use patents, because a generic company that loses in the first round of litigation will have to provide notice to the innovator company if it later files another drug application.  As long as composition or method of use patents are in the Orange Book, the generic drug company must provide notice.

Maybe the inconsistency that only some, but not all, kinds of pharmaceutical patents may be listed in the Orange Book is a minor issue.  Maybe the bigger problem is that the Orange Book exists at all.  Every other company has to continuously monitor the marketplace for potentially infringing products.  And monitoring and testing is expensive for all sorts of high tech industries.  What makes the drug companies special?  Moreover, because the FDA includes any composition or method of use patent in the Orange Book that an innovator company asks it to list, and does not question whether such listings are proper, many patents that don’t belong in the Orange Book are listed there.  This often leads to unnecessary litigation between drug companies.  Maybe a way to bring consistency to FDA regulations is to eliminate the Orange Book entirely.


  • Post author: Aaron Barkoff is a patent litigator at the Chicago office of MBHB. He hold a PhD in Biochemistry from Wisconsin and a JD from the University of Chicago. 
  • Comments are welcome.

19 thoughts on “Editorial: The Orange Book Should Include Process Patents or Be Eliminated

  1. 18

    Aaron, sorry if the last post sounded a little harsh- wasn’t meant to be critical, though you are right in that I don’t like your idea of doing away with listings. Which is strange since I work on the innovator side and the OB benefits generics to a much greater extent.

    For the reasons primarily set out above, I don’t think listing synthetic process patents would benefit anyone on either side. The generics in particular have lobbied hard against this and with good reason- the uncertainty I keep hammering away at.

    Synthetic processes change- often! Dozens and often hundreds of patents issue, often years after launching the drug. Look at any antibiotic in particular if you think I’m exaggerating here. Confusing the issue further is the patenting of intermediate compounds. How would you treat those, since they are normally included as composition claims in most follow on process patents?

    The main reasons though, IMHO, for excluding listing of process patents- the 287(b) inquiry is available to anyone desiring to make the patented compound. The interested party sends a short form letter to the composition patent holder requesting information on any process patents that it knows of. This serves two purposes- first, it tells the generic (or other 3rd party) which processes are protected and which are free to use (assuming more than one way to synthesize exists). Second, it alerts the NDA holder of an upcoming generic filing before it happens- allowing intelligence to be gathered prior to the filing so that sound business decisions can be reached with regard to enforcement of the process patents. Of course, the generic can forego a 287(b) inquiry but then they risk an infringement suit on ANY process patent, which could ultimately delay the generic launch. (I’ve seen this happen several times)

    Detection of infringement of process patents is difficult- under your proposal to list them, the generic would have to certify against the process patents. When they do, how does the patent holder file suit in good faith? In the vast majority of cases, you cannot determine the route by getting a sample of their product and testing it. So do you guess by what process the ANDA product is made? Sue and hope to uncover infringement during discovery? What happens if you determine they previously infringed the process but their current process doesn’t infringe? What about 3rd party process or intermediate patents (licensed or not)? The list of variables could fill pages, believe me. What if the infringement is on an older process patent that you no longer (or perhaps never) used? The last case is my favorite- no stay, but a probable injunction, preventing generic launch- it has happened before…3 whole days before the scheduled launch! The EC (I was there at the time!) was NOT pleased to say the least.

    Long and short though- IMHO process patents don’t deserve equal treatment with composition, formulation or approved method of use patents. Remember, if you change the API or the formulation a new 505(b)(1) or (b)(2) is required. Same with a new method of use. But changing the synthetic process doesn’t require a new approval filing with FDA- and a tried and true process already exists for a generic to determine which process patent(s) it may be at risk from.

    Closing thoughts- if all you’ve got to rely on for exclusivity (beyond statutory) is a process patent or five- probably not worth the investment to develop the drug.

  2. 17

    Ok, you didn’t like that idea. How about this one: allow process patents to be listed in the Orange Book. If an innovator drug company represents that a process patent covers its NDA-approved drug, why should that patent be treated any differently than a compound or formulation patent alleged to cover the NDA-approved drug? That thought motivated my post in the first place–equal rights for process patents.

    As you said, improper listing of patents is no longer much of a concern. And if a generic drug company thinks a process patent is improperly listed, then it can request that the process patent be delisted in a counterclaim to patent infringement (just as, pursuant to the 2003 amendments, it can ask for delisting of a compound or formulation patent in a counterclaim to infringement).

  3. 16

    Aaron, to be frank, your proposal to eliminate patent listings from the OB and place on a non-technical district judge the burden of determining whether a patent is sufficiently relevant to merit a 30-month stay would unnecessarily complicate the law, introduce mass uncertainty from a business standpoint for both the generics and the innovators, and harm the public in general by driving up legal costs and perhaps even delaying drug product launches.

    As I stated above, the 30 month stay is NOT automatic under the current law- it is actually the lesser of 30 months or final district court decision, and several have been handed down in less than 18 months recently. And if the plaintiff tries to stall, the court can dissolve the stay and allow the generic to proceed to approval and launch.

    I also don’t know where you formed the conclusion about “game-playing” the listings just to obtain a 30-month stay. The 2003 Act specifies the patent types that are listable, provides fillable forms for listing patents, and limits each listed drug to a single stay- along with introducing rather severe penalties for falsifying information on form 3542. Gaming the listings did occur pre-2003 (most notably making national news in the Taxol cases), but under the current laws forget it- attempting to game the system by listing an improper patent carries serious consequences that no drug company or attorney would care to face. Just for fun(?) I did a little research, and the last 25 new drugs approved by FDA do not list a single patent that claims inappropriate subject matter.

    From a business standpoint, your proposal misses the obvious- the current laws provide business people in both sectors (and the public) with a reasonable certainty as to when they can expect a generic approval and subsequent product launch. Generics could easily end up getting blindsided by secondary patent owners (a fair percentage of new drug patents are licensed from third parties, some of which a generic company cannot discover even after a diligent search). Innovator companies have to bank on the subjective decision of a non-technical judge as to which patents (if any) are “sufficiently related” to the drug (or whatever other subjective standard you set for meriting the stay).

    Forcing a generic company to notify an NDA holder each and every time it amends its application will do nothing but generate endless reams of mainly useless paper, and also may run amok of trade secret concerns.

    Regarding process patents- Generics currently can (and do!) discover process patents for drugs they are contemplating by sending a simple 287(b) letter to the NDA holder. I personally answer about 25 of these letters each year from both generics and chemical supply houses. There is no need, and indeed my colleagues in the generic industry rarely (if ever in most cases!) conduct extensive patent searches, relying instead on the OB lists and the 287(b) letters to assess risk.

    I also don’t know where you came up with your conclusion that apparently spawned this series of posts- that one can somehow do a chemical analysis of a drug substance and thereby discern the process of its synthesis.

    As currently worded (lengthily!), the listing and notice sections of 505(b)(2) and 505(j) are in harmony with 271(e). Or have you forgotten that under 271(e)(1) it is not an act of infringement to make or use a patented drug to generate bioequivalency data? This section did not exist pre H-W.

    You are correct in that H-W was a negotiated Act- it spawned a large generic drug industry that otherwise would not exist because of the uncertainties noted above, and others as well. Dropping OB patent listings would throw a huge monkey wrench into what henceforth has been a workable and for the most part fair set of laws for both sectors of the industry and for the public, which has been the ultimate beneficiary of HW. As I inferred in my first post, the only sector that would benefit from eliminating OB listings and the accompanying laws and regs would be patent litigators.

  4. 15

    Thomas (or anyone), what problems do you see with the following proposal:
    1. remove all patent listings from the Orange Book (the notice function of listing patents is negligible anyway, since generic companies do thorough patent searching);
    2. require every ANDA filer to notify the NDA holder each time an ANDA relating to the NDA-approved drug is filed or amended (now, notice to innovator companies is required only with respect to Orange Book listed patents);
    3. allow the NDA holder to file suit within a certain period of time after receiving such notice; the NDA holder may file suit on any patent–compound, formulation, process, or other;
    4. the district court judge will determine whether a 30-month stay should be granted, based on whether the patent asserted by the NDA holder is sufficiently related to the NDA-approved drug; automatic 30-month stays are eliminated–they’re now discretionary.

    I believe the foregoing proposal has the following advantages: NDA holder can obtain a 30 month stay based on any patent sufficiently related to its approved drug, including process patents; NDA holder receives notice any time the ANDA filer changes which API it uses or how it is made, promoting transparency; no more game playing with Orange Book listings, aimed at earning an automatic 30 month stay.

    The only real disadvantage I see with my proposal is that there may be some uncertainty in whether a patent is “sufficiently related” to an approved drug product–judges would decide. But I think that’s a relatively minor issue compared with the problems of the current scheme.

    I’d love to hear any feedback.

  5. 14

    Just wanting to clear up a few legal inconsistencies with the above posts regarding the FDA Orange Book- First, the 30-month stay is not an absolute guarantee, as stated. Second, not all method of use patents may be OB listed- listing is restricted to FDA approved methods of use. Third, only one stay per OB listed drug is available. Fourth, OB listing is not restricted to the NDA owner.

    A thorough discussion of Hatch-Waxman legislation and the regulations surrounding the statutes could fill a few tomes (and indeed it does!). Having worked in the pharma industry since just before H-W was enacted, one thing is certain- there is something in these laws and regs that upsets anyone who deals with it on a regular basis. Unfortunately, the suggestions advanced (either include hundreds of mainly irrelevant process/other patents or eliminate the OB altogether) would take us all back to the bad old days…of course, the litigators thrived in the pre-OB days…:-)

  6. 13

    Hi Aaron.

    Like you, I am speculating as to the reasons the FDA has included the patent information in the Orange Book. I don’t have a window into their collective thoughts on the subject, or at least don’t wish to spend the time to see if one is available to me. David seems more conversant with the Congressional History of Hatch-Waxman, perhaps he would be kind enough to throw some light on the matter.

    I do however believe that we should try to keep the speculation within the bounds of the FDA’s mandate, at least initially. That is the only reason I made my suggestions. As you might recall, I also suggested that the information was there gratis. Possibly through the work of innovator drug company lobbyists.

    Conspiracy? Well, you have indicated it is your belief that the innovators got together with the generics to decide what the Orange Book would contain and how Hatch-Waxman would be implemented. This could only happen with Congressional approval and FDA capitulation. So in your scenario there are at least three parties involved. That’s one more party than you need to describe their actions as a conspiracy.

  7. 12

    Don, I understand that you’re trying to identify FDA policy reasons for including patent information in the Orange Book–I am too. I’m surprised that, as you report, one policy reason stated by the FDA is that it wants to provide clarity as to the nature of the approved drug.

    Why do I think one reason the Orange Book includes patent information is that it provides notice to generic drug companies? Because the Orange Book only lists UNEXPIRED patents. In fact, if the FDA were more concerned with clarity, you’d think they would list expired patents too.

    Finally, I don’t know what conspiracy theory you’re thinking of. I certainly didn’t mean to suggest one.

  8. 11

    Aaron, I think the crux of the disagreement on this issue is, as David pointed out, an undue focus on the effects of current policy on innovative drug companies. When I remarked that the real benefit of the patent information is that it may provide clarity as to the nature of the pharmaceutical or method being listed, I was attempting to identify FDA policy reasons for including the information. I agree with you that the information can be used for purposes other than the FDA’s intended purpose, but that really isn’t relevant to why the Orange Book is what it is. The fact there are alternative uses of the information for drug companies and the informational content could be altered to create additional use doesn’t negate the reason the information provided is there in the first place. What the drug companies choose to do with the information outside regulating pharmaceuticals is not a concern of the FDA. I don’t think the FDA has shaped its application of the Hatch-Waxman Act to suit either the “innovative” drug companies, or the “generics.” Apparently you do.

    I don’t wish to belabor the point, but for example you state that:

    “I think one purpose of the patent information is to provide notice to generic companies of patents covering approved drugs, so the generics can decide which project to invest their R&D dollars in and when. For the same reason, the Orange Book includes FDA exclusivity information, such as orphan drug and pediatric exclusivity info.”

    My question is why do you think this?

    First, using the patent information in the Orange Book in the manner you suggest makes that information redundant. It’s publicly available from other sources, and easily searched. Even if proprietary databases are used, the search cost is negligible in comparison to the cost of paying someone to analyze the patents. Even worse, the Orange Book “notice” you describe is meaningless. The Orange Book is not an exhaustive list of current US patents on pharmaceutical compounds or their uses. Any responsible generic is going to have to do a more exhaustive search than the Orange Book before embarking on production of a drug. It just doesn’t make sense to include patent information in the Orange Book for the reasons you suggest.

    Second, as has been previously pointed out, there are several sound policy and legal reasons for limiting the information in the current manner. All of the reasons presented are within the mandate of the FDA and consistent with Hatch-Waxman. Why then is it necessary to argue that the FDA has exceeded its mandate and resort to a conspiracy theory in order to explain current policy? I may be wrong, but I suspect the FDA isn’t interested in generic drug company spending or whether an NDA holder gets a 30-month stay. Certainly as a citizen, I hope that isn’t their motivation.

    Third a principle goal of the Hatch-Waxman Act, and more particularly ANDAs, is to accelerate generics to market. I am not so naïve as to think that horse-trading with lobbyists isn’t a part of lawmaking, but it would be very disturbing indeed if drug companies intended by Congress to be regulated by a law could hijack that law in the manner your article and posts suggest. Even worse, in this case, ex post facto.

    Have a nice weekend.

  9. 10

    Don, you’re absolutely right that listing patent information about approved drugs is not the primary purpose of the Orange Book. But I disagree with your statement that “The real benefit of the patent information is that it may provide clarity as to the nature of the pharmaceutical or method being listed.” There’s plenty of information regarding the drug and indications in the label, which is made public upon approval of the NDA. The label provides sufficient clarity as to the nature of the drug and its uses. In fact, the patents probably only confuse the issue, because they contain way more information than the FDA even receives in the NDA.

    I think one purpose of the patent information is to provide notice to generic companies of patents covering approved drugs, so the generics can decide which project to invest their R&D dollars in and when. For the same reason, the Orange Book includes FDA exclusivity information, such as orphan drug and pediatric exclusivity info.

    But another reason for including patent information in the Orange Book is to make it easier for NDA holders to get their 30-month stays. I imagine the Hatch-Waxman negotiations between the two industries went something like this: the generics wanted to free ride on the innovators’ safety and efficacy data (by proving mere bioequivalence) and they wanted a research exemption so they could do their bioequivalence studies before patent expiration; in exchange, the innovators wanted a 30-month stay of generic approval; the innovators probably wanted to trigger the 30-month stay any time they sued a generic company on ANY patent relating to its NDA-approved drug (after filing a lawsuit, perhaps the court’s first decision would be whether the patent relates to the NDA-approved drug); the generics came back and said no, you can only trigger the 30-month stay by suing on a compound or formulation patent–not ANY patent–and moreover we must get advance notice of those patents (by listing them in the Orange Book); the innovators agreed, on the condition that the 30-month stay would be AUTOMATIC, upon filing a lawsuit relating to an Orange Book listed patent–a judge wouldn’t decide whether the patent was sufficiently related to the NDA-approved drug.

    I was unclear in my first post. I din’t mean to suggest eliminating the Orange Book entirely, only the listing of patent information in it. Then, instead of the generics certifying only as to Orange Book listed patents, they could be required to provide notice to NDA holders any time they file or amend an ANDA. If the innovator decides to sue the generic company, a judge could determine whether the patent is sufficiently related to the NDA-approved drug to warrant a 30-month stay. There would be no more automatic 30-month stays.

    Yes, I realize the innovators wouldn’t like losing automatic 30-month stays. But they would be happy if they could get a 30-month stay on any patent relating to their approved drugs, including their process patents. Moreover, they’d be happy if the generic company had to provide notice every time they file or amend an ANDA. That way, the innovator wouldn’t have to do continuous chemical testing of the generic drugs on the market.

  10. 9


    Read through your last comment to me and consider it in terms of admissions and estoppel. I’m using admissions a bit loosely here since the generic applicant will have asserted why it is not infringing the patent as part of the paragraph 4 certification and notification provisions.

    “Formulation patents are often limited in scope to the precise formulation marketed by the NDA holder. Generic drug companies have lots of excipients to choose from when designing around these narrow formulation patent claims.”

    With respect to the first part, precisely. The generic applicant in a 505(b)(2) or 505(j) application is asserting that their compound or compound/method of use combination is equivalent to the one first reviewed in the approved NDA. With respect to the second part, I disagree. You are arguing that the patent owner has failed to claim an easy equivalent, or that the generic applicant is asserting an equivalence that is unlikely to pass muster with the FDA. Those are the exceptions, and not the rule.

    “But I think there’s just as much reason to presume that a generic drug company has infringed a process patent as there is to presume that the generic has infringed a formulation patent.”

    I disagree. The presumption arises because the generic applicant is admitting/asserting equivalence of the compound or compound and method. The presumption was not created out of whole cloth. There is no reason to presume that the the generic applicant is infringing the process patent absent an admission/assertion of equivalence of process anymore than there is reason to presume that the manufacturer of an infringing non-pharmaceutical product infringes the process for making that product. It could be an inference, but it is not a presumption based an objective analysis of experience. I do not believe that you will find many chemical engineers that agree with your view on this point.

    The scheme does not exist simply because patent holders wanted it to be that way, as evidenced by the 505(b)(1) NDA mechanism. The scheme exists to accelerate legal relief arising out of the generic applicant’s own statements, with judicial review serving to reverse the relief rather than initiate the relief.

  11. 8

    A compound or a formulation is the final product for a particular drug. It is easy to identify which patent covers it, even to a polymorph under the current rule. However, it is different for a process. There may always be a new process patentable. Under the old rule, if a process patent could be listed in the Orange Book, it could create a situation of forever 30-month stay. Maybe that’s why a process patent originally was not on the list. The new rule only allows one 30-month stay; however, if a process patent is allowed in the orange book, a drug company could list as many process patents as possible by its own research or by licensing, to make it formidable for a generic company.
    For a drug company, is it always better to list more as long as it does so in a good faith?

  12. 7

    David, I don’t disagree with your interpretation of Hatch-Waxman or its history. But I think there’s just as much reason to presume that a generic drug company has infringed a process patent as there is to presume that the generic has infringed a formulation patent. Often, the innovator drug company has put a lot of research into developing the most cost-efficient process for making the API, and has patented that process. To compete best in the market, the generic drug company will want to use that patented process. At the same time, formulation patents are often limited in scope to the precise formulation marketed by the NDA holder. Generic drug companies have lots of excipients to choose from when designing around these narrow formulation patent claims.

    Again, I think it must have been some type of legislative bargain struck between the innovator and generic companies that’s keeping process patents out of the Orange Book. Maybe that’s no so bad, since if they struck a bargain that means they reached agreement. On the other hand, the regulations seem logically inconsistent.

  13. 6

    Hi Aaron:

    Thank you for taking the time to write your article.

    For those who might read this and not be familiar with the Orange Book, lets clarify exactly what the Orange Book is. The Orange Book doesn’t simply contain information about patented products. The Orange Book contains information on all FDA-approved drug products and therapeutic equivalence evaluations. The purpose of the Orange book is to provide public notice as to FDA-approved pharmaceuticals. The Orange Book has nothing to do with patent infringement notification per se. In fact, the patent information is arguably gratis and to the benefit of innovator drug companies. The real benefit of the patent information is that it may provide clarity as to the nature of the pharmaceutical or method being listed.

    Getting to your e-mail questions, the short answer to your first question is that it doesn’t. However the question is a bit like asking why do cancer patients take chemotherapy when it makes them nauseous. Notification of potential infringement is a bi-product of the reporting requirements leading to Orange Book registration. It is the Federal registration process and the public policy behind it that is the determining factor in reporting, not the convenience of the “innovator” drug companies.

    “Jenny” is absolutely right. There is a multitude of ways to produce most compounds. To attempt to include all of them in the Orange book is not only pointless to the purpose it was designed to address, but arguably antagonistic to it. As inclusion of processes does not address the purpose of the exercise, there is simply no reason to tie process disclosures to it.

    As to the second question of your response, the short answer is “so what?” The vast majority of patent holders (should) monitor their market place. I don’t see where the burden is. We really are not talking about two classes of patent holders here either. The “innovator” drug companies that you suggest are burdened are actually the ones getting a free ride on the Orange Book with respect to compositions and methods for their use. The real question is, why is one industry getting preferential treatment in patent enforcement when other industries have to go it alone? In fact I suggest to you that if your thesis were adopted, and the Orange Book was eliminated because it doesn’t contain process patents, the biggest outcry would come from the innovator drug companies that are allegedly so burdened.

    The second burden you mention is testing of drug samples to identify an infringer. Assuming that the reporting requirements currently in place actually work as intended, how is this a burden? If the company was enforcing a composition claim they would test a sample as part of their due diligence prior to trial anyway. The drugs at issue will be in the Orange Book. Therefore the only burden is monitoring the periodic supplement to the Orange Book, which is nothing more than good business practice if you are a pharmaceutical company.

    While I disagree with your conclusions, I have to thank you again for presenting your article. It has made me think a little bit about the ‘hows and whys’ of the Orange Book, and provided some recreation from daily law practice. All we can ask of our authors is that they entertain us a little or make us think. The efforts of you and Dennis provide the rest of us with both.

  14. 5

    To Jenny — But the Orange Book would list only those process patents owned or licensed by the NDA holder, just as the Orange Book now lists only those compound or formulation patents owned or licensed by the NDA holder. There’s no need to list any other process patents, just as there’s no need to list any formulation or polymorph patents concerning the API that aren’t owned by the NDA holder. The Orange Book doesn’t list all patents relating to a particular drug; it lists only those patents owned by the NDA holder relating to the drug.

  15. 4

    I believe that part of the confusion that is being expressed results from an undue focus on whether drug patent holders are required to search the market for potentially infringing products or not, rather than an analysis of the meat of the Hatch-Waxman act.

    The search or lack of a search is not the point. The automatic 30 month stay on ANDAs and NDAs which rely on third party clinical data is the point. The patent holders have convinced Congress that it is appropriate to presume that in such applications the competing drug or method of use infringes an existing patent, and that it would be an excessive burden to require the patent owner to seek preliminary injunctive relief. Otherwise, should the generic drug application be approved and the drug enter the market, the NDA holder potentially suffers irreparable harm through lost sales, uncertainty in company valuation and stock price, etc.*

    Whether you agree or disagree with this policy choice, I believe that the argument is far weaker in the case of process patents. Simply, in a 505(b)(2) NDA or a 505(j) ANDA the applicant is asserting that the composition or method of use is equivalent to the composition or method of use that has been approved in a prior NDA. It’s a classic estoppel. Yet in the case of a process, the applicant asserts nothing about the process other than the fact that it produces a safe and effective composition. Process regulation is distinct from the Hatch-Waxman provisions. In addition, it appears that Congress has determined that there is a greater likelihood that the applicant has designed around any process patent, so that it is inappropriate to award the patent owner an automatic 30 month stay of FDA approval. Instead, the patent owner must seek traditional preliminary and/or final relief.

    If you disagree with this interpretation of the statute and its history, then consider this: there is no requirement for an applicant to notify patent holders and include a paragraph 4 certification in NDAs that do not rely upon third party clinical data. A generic drug applicant can file a 505(b)(1) application and “simply” avoid the possibility of a 30 month stay. Obviously, filing an NDA is not simple, yet I find it hard to believe that the patent owners and Congress simply forgot about such a loophole given the immunity for regulatory R&D in 35 U.S.C. 271. Instead I would argue, again, that Hatch-Waxman provides an estoppel-based mechanism for preliminary relief that doesn’t logically reach the issues in process of manufacture issues.

    * I wish to make it clear that I am not expressing an opinion on this point. I am simply attempting to summarize the legislative history of Hatch-Waxman in a very small space. The progress of drug development under Hatch-Waxman provides both sides with evidence-based arguments for and against the current scheme.

  16. 3

    For each drug, there are many many synthetic routes for it. It is impractical if process patents are listed in the orange book.

  17. 2

    Thanks for your comments.

    I’m a little confused. How does requiring a generic drug company to notify an innovator drug company that it possibly infringes the innovator company’s compound or formulation patent help protect the public from dangerous drugs? It seems to me that the only purpose of the notice requirement is to help innovator drug companies file lawsuits.

    With regard to your second point, even if it is true that process patent owners are cut some slack after the lawsuit is filed, they still have to continuously monitor the marketplace and test samples of drugs, looking for evidence of infringement of their process patents before they file a lawsuit. But compound and formulation patent owners have no such burden to monitor, because generic drug companies are required to provide them notice when they file or amend their drug applications.

  18. 1

    Perhaps the reason process claims are not included in the Orange Book is because the process of making the compound has little if any effect on the efficacy of the drug (assuming the ultimate composition is not materially different from the patented composition, in which case it probably isn’t infringing anyway).

    The purpose of the FDA in our context is to protect the public from dangerous pharmaceuticals, not police the patent jungle for big pharma. Notice provisions for pharmaceutical compositions and methods of use go towards fulfilling that role. Methods of production generally will not.

    Besides, in the case of manufacturing processes, an infringement action is frequently warranted on lesser evidentiary showing prior to trial because the evidence necessary to prove infringement is almost always solely within the control of the defendant. In such cases the plaintiff is generally entitled to some discovery prior to summary judgment motions being heard, and isn’t likely run up against sanctions unless no due diligence was exercised prior to trial.

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