Abstract
US Legal and Regulatory Update
Compiled and written by Greenblum & Bernstein, PLC
A US intellectual property law firm which provides a full range of services in IP-related matters across all industries, including the biotech and pharmaceutical industries, including:
Inter partes Review (IPR) and Post Grant Review (PGR)
Abbreviated new drug applications (ANDAs) and Notice Letters
Patent and trademark litigation
Patent drafting and prosecution
Patent infringement and validity opinions
Patent reexamination proceedings and interferences
New drug strategies
Market entry strategies
Joint venture strategies
Licensing
This section is intended to be a synopsis of recent developments and is not intended to be exhaustive. If any issue is referred to in this section is to be relied upon, specific advice should be sought. Please contact:
Paul A. Braier, PhD, Esq
Greenblum & Bernstein PLC
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Reston, VA 20191
USA
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Introduction
As those in the pharmaceutical industry know, it can take many years from when a candidate drug is first identified until it finally receives marketing approval from the relevant regulatory authority. Most candidate drugs never get marketing approval, having failed any of numerous non-clinical and clinical studies along the way.
While a drug candidate is being developed and moves along the regulatory track, another track is also running somewhat independently: 1 the patent track. The drug sponsor has undoubtedly filed one or more patent applications covering aspects of the drug itself, its manufacture, its formulation, and/or its method of use, etc. But the sponsors sometimes find that one or more patents are granted before regulatory marketing approval is approved. Any patent term during the time after the patent issues, but before the drug receives regulatory approval, drug sponsors generally consider to be “lost” patent protection.
In the US, the Patent Term Extension (PTE) statute 2 was codified and enacted in order to compensate drug developers for some of the patent term “lost” before marketing approval is granted by the U.S. Food and Drug Administration (FDA). The law was passed in 1984 as part of the much larger groundbreaking Hatch-Waxman amendments that also enacted the Bolar Amendment, and gave birth to the modern generic drug industry.
Despite being over 30 years old, some aspects of the PTE often seem to be misunderstood or unappreciated in the generic and biosimilars industries. Because of some recent changes in how the U.S. Patent and Trademark Office (USPTO) handles PTE procedures, this seems like an opportune time for a fresh overview.
The PTE statute is complicated, with many provisions, procedures, special cases, and exceptions. This article is not intended to be an exhaustive review of all the intricacies and nuances of the PTE statute and its associated procedures. Rather, this article is intended to present a “big picture” review of the PTE to those who may be most impacted by PTE extensions—such as generic drug and biosimilar applicants.
Eligibility for the PTE
To receive a PTE extension, both the product itself, as well as any candidate patent(s), must meet certain conditions. The PTE application procedure is done through the USPTO, with input and assistance from FDA. A PTE application is part of the public record and is made part of the prosecution history of the patent. It can be obtained or followed through the USPTO Public Patent Application Information Retrieval website (https://portal.uspto.gov/pair/PublicPair).
Products for which PTE may be sought
The PTE statute defines a “product” for which PTE is eligible as any drug product, or any medical device food additive, or color additive subject to regulation under the Federal Food, Drug, and Cosmetic Act (FDCA). 3 The term “drug product” is defined to include the active ingredient of a new drug, an antibiotic, a human or veterinary biological product, or a new animal drug, including a salt or ester of the active ingredient. 4 Thus, the range of products for which a PTE is potentially available is huge, including not only human drugs (e.g. new drug application (NDA) products) but also biological products, certain medical devices, 5 and many other products.
However, not all products qualify to have a patent extended. As a general matter, the permission for commercial marketing must be the first marketing permission granted for the product. 6 For example, for a human drug having New Chemical Entity status could be eligible to have a patent receive a PTE. For a combination product (having two or more active ingredients), as long as at least one of the active ingredients has not been previously approved, the product should be eligible for a PTE.
That the “drug product” includes the active ingredient as well as any salt or ester of the active ingredient can also have an impact on eligibility. A newly approved ester or salt of a previously approved acid or base can be eligible for PTE. 7 However, due to what is likely an unintentional loophole in how the statute is written, the reverse is not true—a newly approved acid or base of a previously approved salt or ester is ineligible for PTE. Moreover, an enantiomer of an active ingredient may be eligible for PTE even when the racemate was previously approved. 8
Patents for which PTE may be sought
Eligible patents include patents with claims directed to the product itself, to a method of using the product, or even to a method of manufacturing a product. Patents directed to manufacturing are likely more important in the areas of biologicals and medical devices, but there is at least theoretically no reason to preclude extending a patent directed to a method of manufacturing a human drug. A patent does not need to be eligible for listing in the Orange Book (for a human drug), or listable in a patent dance (for a human biological) to qualify for a PTE extension. 9
A patent otherwise eligible for extension must also meet several other criteria, including that it must not have expired before the PTE application is filed; the patent must not have previously received another final PTE extension; the associated product must have been subject to regulatory review prior to commercial marketing or use; and the PTE application must meet all statutory requirements (including that it be filed within 60 days of product approval). 10
The condition that the patent not have expired can be a problem when studies and regulatory review take so long that the patent is near expiration, or is even expected to expire before the product is approved. Therefore, the law provide for two types of “interim extensions.”
The first type of interim extension applies when the patent is expected to expire after the product application (e.g. the NDA or BLA) is filed, but before FDA approves the product. In that case, the patent owner may request the USPTO to grant an interim extension under 35 U.S.C. § 156(d)(5). Among other things, the application must be made no sooner than six months before the patent expires, and no later than 15 days before it expires. The USPTO, upon review of the § 156(d)(5) application, may grant an extension of up to one year, 11 which can be extended for up to four subsequent interim extensions. 12 Any such interim extension expires automatically 60 days after product approval unless the applicant files information sufficient to effectively convert it to a regular PTE application. 13
The second type of interim extension applies when the PTE application has already been filed, and the patent is expected to expire during pendency of the application. In that case, the USPTO is required to automatically extend the patent term for periods of up to one year. 14
Term of an extended patent
The length of the extension is determined by the regulatory review period, which itself is divided into two parts. For convenience, we refer to these as the “testing phase,” and the “regulatory approval phase.” The testing phase is the period during which FDA has granted authorization to perform clinical studies for evaluation of the product. For a human drug, this is the investigational new drug period. For a Class III medical device, this is the investigational device exemption period.
The regulatory approval phase is the period that begins when the application for FDA approval is filed, and ends upon approval of the application. For a human drug, this is the NDA period, and for a medical device this is the premarket authorization period. Whether the product is a human drug, biologic, or medical device, the regulatory approval phase does not begin until the application in question is complete (e.g. for a medical device, all required modules must be filed).
The initial determination of the length of the extension can be obtained by adding the length of the testing phase to the length of the regulatory approval phase, followed by subtracting one-half of the testing phase. 15 When doing this calculation, any portion of time before the patent issued is disregarded. While FDA is also required to subtract any period during which the applicant did not act with due diligence, such instances are rare.
The extended patent term is obtained by adding the above period to the “original expiration date” of the patent, 16 which includes any patent term adjustment made under 35 U.S.C. § 154(b) for USPTO delays in prosecution. 17
The period of time calculated as above is the maximum amount of time that the patent can be extended. This period of time may be shortened if either (or both) of two conditions hold. First, the extension cannot extend the term of the patent beyond 14 years from the date on which the product was approved. 18 Second, the maximum permissible extension is five years from the “original expiration date” of the patent. 19
Recent developments
While only one patent may be extended for a particular product, the statue does not preclude filing of PTE applications for more than one patent. Sometimes, in the face of various uncertainties, some applicants have filed multiple PTE applications for various patents alleged to cover a product (or its use or manufacture).
Reasons for filing multiple applications are varied. For example, the applicant may be uncertain early in the process what the final approved use(s) will be. Or there may be an issue of validity that the applicant wants to review through a re-examination procedure. Or another party might have filed a request for inter partes review or post-grant review of a patent, and the applicant is uncertain whether the patent will survive the procedure. Whatever the reason, only one PTE application can be granted, hence when multiple PTE applications are filed relating to a single product, the applicant must ultimately select which one patent to extend, and abandon the other applications.
At some time during the early years of the PTE statute, the USPTO had occasion to address the situation where a PTE applicant had filed multiple applications, at least one of which included an interim patent extension. At that time, the USPTO determined that an interim patent extension is a type of patent extension, and since the statute only permitted one PTE, an interim patent extension precluded the filing of any other PTE applications.
However, it appears that the USPTO has recently revised its policy concerning multiple interim PTE petitions for patents that may expire before final approval of the application is granted (i.e. requests for two or more interim extensions relating to the same product). In view of certain reports concerning multiple interim extension applications, the author made inquiries at the USPTO Office of Patent Legal Administration.
Apparently, the USPTO formulated its former policy when the relevant portion of the PTE statute read “in no event shall more than one patent be extended for the same regulatory review period for any product.”
20
However, this portion was amended in 1994 to read “in no event shall more than one patent be extended
Recently, however, at least one PTE applicant brought this to the USPTO’s attention regarding interim extensions under 35 U.S.C. § 156(e)(2) (applicable when the patent is expected to expire after the PTE application is filed, and before it is granted). The USPTO has now changed its position at least with respect to multiple interim extensions under 35 U.S.C. § 156(e)(2). Although it is not known if the USPTO has applied the policy change to multiple interim extensions under 35 U.S.C. § 156(d)(5) (where patents are expected to expire before FDA product approval), it appears the same reasoning should apply.
Conclusion
The PTE statute can extend patent coverage over a very wide range of important drugs, biologics, medical devices, and other products. Given some new developments in PTE applications, it is possible that the number of PTE applications will soon begin to rise. The PTE application procedure can take several years, which means that for several years, a potential competitor (e.g. generic or biosimilar) may have an increased number of PTE applications to monitor. Even though only one patent can ultimately be extended per product, an increased number of applications also means that the generic/biosimilar may have to devise several contingencies since it may not be known for years which patent will actually be extended. It is important for generic and biosimilar applicants to understand how the FDA’s new policy on multiple interim extensions can affect strategic considerations of product development.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Notes
Author biography
Paul A Braier is a shareholder at Greenblum & Bernstein, P.L.C., a full service patent and trademark law firm. Dr. Braier has been with Greenblum & Berstein for over 20 years and has special interest in Hatch-Waxman, pharmaceuticals, chemicals, and medical devices. He received his J.D. from Georgetown University Law Center and his Ph.D. in chemistry from the University of Chicago.