13 years ago

This article is the first in a series by Hultquist IP on the interaction of U.S. patent law and U.S. FDA law.  In this article, we focus on patent strategies that a pharmaceutical company might employ.

There are many ways to claim pharmaceutical inventions.  The type of claims that are pursued typically mirror the stage the research is in at the time the patent is filed. 

Typically, the first step in inventing a blockbuster drug involves identifying a biological pathway that is associated with a disease state.  For example, one can determine that a particular receptor, enzyme, and the like are implicated in the development of a disease, and that by modulating the receptor, or the amount of enzyme that is produced, one can control one or more of the onset of the disease, the progression of the disease, or the symptoms of the disease.   

Patent applications filed on this aspect of an invention may focus on genetic material that encodes the receptor or enzyme, vectors used to transfect cells with this genetic material, cells transfected with this material, and high throughput screening assays using cells that are genetically modified to express the receptor or enzyme.  By filing this type of patent application, a company can obtain a proprietary position that can be used to inhibit others from identifying compounds that might treat the particular disease. 

There are several limitations associated with “screening tool” patents.  It takes a significant amount of time to get a patent, and it is difficult to obtain damages related to activities that occurred before the issuance of the patent.  Where a competitor has already identified a lead compound before the screening method patent issues, the patent claims are not infringed by the manufacture, use, sale, offer for sale, or importation of the compound.  Even if a patented screening method was used to identify a lead compound, it can be difficult to prove that the method was used. 

When a screening method patent is litigated, the damages are also relatively limited.  Typical damages in patent litigation include injunctive relief and monetary damages.  While injunctive relief can prevent a competitor from continued use of the screen, it will not prevent a competitor from pursuing FDA approval of a drug that has already been discovered.  Further, in terms of monetary damages, courts have typically limited the awards to a hypothetical licensing fee that would have been received had the parties negotiated in good faith before the patent litigation.  Patent litigation is a costly process, and there is always risk that a patent will be invalidated, e.g., on the basis of prior art that is located by the putative infringer after the patent is issued, and that was previously unknown to the patent owner and its attorneys. Thus, patent litigation entails significant risks, and in some instances the costs of litigation can exceed the amount of the damages recoverable even if the patent holder is otherwise successful in prosecuting the infringement.  Accordingly, the decision to undertake litigation should be carefully considered and fully informed by advice of counsel.

The next step in the process typically involves screening combinatorial libraries of compounds, and identifying the active compounds.  This process is known as lead generation.  Typically, these initial leads are not the best compounds that could be furthered in clinical studies, but serve as a good starting point for preparing and evaluating additional compounds that are structurally similar to the initial leads.  This process is known as lead optimization. 

Patent applications are typically filed at the lead generation stage, and the structures of the compounds that are identified during lead generation are used to prepare broader general chemical structures, where the modifications of the compounds are expected to result in similarly active compounds (even if such compounds have not yet been tested).  These patents, by necessity, include relatively broad claims, and are intended to keep out competitors that might otherwise identify active compounds that fall within the general structures.  There are, however, some potential downsides associated with these early patent filings. 

The U.S. Patent and Trademark Office, and patent offices around the world, typically reject broad claims on the basis that the specification includes limited support, and may not adequately support claims directed to broad chemical formulas.  To address this concern, it is a good idea to include fall-back positions where such can be easily identified, include claims of varying scope, and including prophetic assays wherein a putative compound can be screened for activity.    

The early filing also starts the 20 year clock for patent term, and to the extent that future patent applications are filed on individual lead compounds, the earlier patent applications, with relatively broad disclosures, are available for purposes of obviousness.  However, since the lead compounds that are ultimately pursued for clinical trials are typically the very best in class, with the most activity and fewest side effects, it is frequently possible to overcome obviousness rejections raised on claims to such compounds. 

After lead generation and lead optimization studies are completed, companies frequently pursue additional patent protection on the identified leads.  The patent claims are typically much narrower in scope, but the actual lead compounds to be pursued in clinical trials may not have been identified at this time. 

Putative leads are then frequently put into animal studies, where the biological activity and/or toxicology can be evaluated.  The results of these studies give companies the information they need to file an Investigational New Drug (“IND”) application with the U.S. Food and Drug Administration (USFDA).  By the time the IND is filed, companies have usually identified the absolute best compound in the class, and several backup compounds (in case clinical trials reveal adverse side effects, lack of efficacy, or other limitations associated with the lead compound).  It is often useful to file an additional patent application to claim the very specific lead compounds, so that patent term can be maximized.  There are several advantages to this approach. 

First and foremost, during litigation, it is frequently easier to invalidate a broad patent claim than a narrow patent claim.  “Picture claims,” which are directed solely to the identified lead compounds, can be relatively difficult to invalidate.  Plus, the claims are filed later on in the patent lifecycle, so may afford a longer term of patent protection. 

When considering the benefits of an earlier filing with broad claims, and a later filing with narrower claims (including picture claims), it is important to consider the following.  Under the provisions of the Hatch-Waxman Act, only one patent can be extended for each approved drug product.  There is a maximum of five additional years of patent term, for a maximum fourteen years of patent exclusivity.  By the time the drug product is approved for sale by the USFDA, a patent issuing from the earlier-filed application, with broad claims, may be entitled to the entire five year extension.  A patent issuing from the earlier-filed application may not be entitled to any extension, particularly if the drug approval occurs at a time where the patent has more than fourteen years of remaining term.  The exact circumstances will vary from case to case, but this type of scenario is not too uncommon.  For this reason, it is wise to pursue a variety of different of patent applications, at different times, with claims of different scope, and to consult with patent counsel before deciding which patent to extend upon drug approval. 

After successful animal studies, most drug companies begin to prepare to file an NDA with the USFDA.  This is a particular point in time when it is absolutely critical to coordinate between FDA and patent counsel. 

As discussed above, if a drug is approved, a single patent claiming the drug product, or method of using the product to treat a particular disorder, can be extended under the provisions of the Hatch-Waxman Act.  The discussion above related to the amount of extension that might be available.  This is an important consideration, but to even get to this point, there must be a patent to extend.  The extension does not begin to toll until two triggering events occur – an NDA is filed, and a patent has issued.  Thus, it is important to obtain patent issuance either before the NDA is filed, or as soon as possible afterward.  For this reason, it is important to advise patent counsel well in advance of anticipated IND filings. 

Frequently, during prosecution, an Examiner will agree to allow narrow claims, but not broad claims.  It is often possible to abandon broad claims to gain a rapid allowance of narrow claims, and pursue the broad claims in a continuation application.  One can obtain patent issuance sooner, frequently by a year or more, using this approach.  The delay associated with fighting for broad claims may result in the loss of a half year or more of patent term extension.  Accordingly, there is value in pursuing the broad claims in a continuation application, as well as taking other appropriate steps to expedite patent issuance, such as paying the issue fee as soon as possible after a Notice of Allowance is mailed.  Patent attorneys can consider these options if they are provided with advance notice of an upcoming NDA filing, which underscores the importance of involving patent counsel early on. 

Are there downsides to cancelling broad claims in favor of narrower claims?  Certainly – there will be delays in obtaining the broad claims, and the company will have to prosecute and maintain more patents than if all claims are pursued in a single application.  However, the main competition is frequently a generic drug company, and a narrow claim that covers the approved drug product is frequently all that is needed to keep them at bay. 

The above discussion relates to approaches taken from the time a bioassay is developed through the time an IND is submitted.  This is not the end of the story.  Companies frequently discover new patentable subject matter during clinical trials, including optimal dosage ranges, novel salt forms, synthetic methods, combination therapy, pseudomorphs and polymorphs, formulations that provide appropriate drug delivery, and the like.  These discoveries may be patentable, and can be used to provide additional patent term.  For this reason, we typically advise clients to carefully review the results obtained following Phase I, Phase II, and Phase III clinical studies, and meet with patent counsel to identify additional subject matter that can be protected.  In this manner, companies may obtain patents that extend beyond the term of the initial patents covering the drug itself, or methods of treatment using the drug.

After the clinical trials are completed, the company then files a New Drug Application (“NDA”) with the FDA, and it takes around a year or more for NDA approval.  During this time period, it is vitally important for drug companies to consider which patent they want to extend under the provisions of the Hatch-Waxman Act.  After you receive FDA approval, you have only sixty days to file for a patent term extension, and there are a number of hurdles to jump through.  It is best to have the documentation prepared well in advance of FDA approval, because the consequence of missing the deadline is the potential loss of five years of patent term.  For a blockbuster drug, this can be a loss of billions of dollars in revenue.  Accordingly, this is another time when it is advisable to involve patent counsel well in advance of the applicable deadline. 

Finally, when obtaining a patent portfolio surrounding a particular drug product, it can be useful to have periodic meetings to review the patent portfolio, including “ideation sessions” and IP audit meetings, to ensure that all steps are being taken to properly protect the drug product. 

Patent protection is extremely costly, and it can be important to focus on the most important patent properties.  Frequently, a drug program is cancelled, because of side effects, or other factors, but the patent attorneys are not advised that the program is cancelled.  If the patent attorneys are not kept in the loop, a company may incur significant additional fees to maintain patent applications of little or no value to the company.  By conducting periodic IP audit meetings, and including stakeholders, such as business development, general counsel, chief scientists, and the like, a company can ensure that it is pursuing those cases that offer the most value, and abandoning those cases that offer the least value.  By conducting ideation sessions, a company can ensure that it has identified all discoveries that are, at least potentially, worth pursuing.  This can help a company with its patent lifecycle management, which is particularly important when a company’s earliest-filed patents near expiration.  

In future articles, we will discuss patent litigation issues associated with patents related to pharmaceuticals, including patents claiming compounds, compositions, methods of treatment, methods of synthesis, and research tools.  

If you have any questions, please do not hesitate to contact Hultquist IP.   

David Bradin

June 17, 2011