Pharmaceutical Patent Term Extension: An Overview

Pharmaceutical Patent Term Extension: An Overview

About the authors: Scott Whittaker is an Alacrita Associate and Robert Johnson is Managing Partner of the firm’s Boston office. Anthony Walker is a Managing Partner in the firm’s London office.

Introduction

A period of market exclusivity is critical for most novel pharmaceutical products and the duration of that exclusivity has a direct impact on the value of a pharmaceutical asset. There several forms of exclusivity that can apply to pharmaceutical products. This overview is a summary of one of them: the patent term adjustment.

I. OPTIONS FOR LENGTHENING THE TERM OF A PHARMACEUTICAL PATENT

From the date a patent application is filed, various events can delay the time it takes for the application to mature into a patent. When certain types of delays are caused by the PTO, some or all of the time that is lost can be regained through patent term adjustment (PTA). Delays caused by the U.S. Patent and Trademark Office (PTO) in the initial examination of biotechnological and pharmaceutical patent applications are particularly onerous.

Once the patent issues, further delays that effectively reduce the period during which the patent has commercial value may be encountered-for example, in situations in which Food and Drug Administration (FDA) approval must be obtained before a patented drug product can be marketed in the United States. These types of delays can be compensated for by patent term extension (PTE). PTAs are applicable to all patents but are especially pertinent to biotechnological and pharmaceutical patents because of their protracted prosecution, which is usually attributable to both delays in PTO examination and the relatively complex prosecution associated with such applications.

II. DETERMINING WHEN A PATENT IS ELIGIBLE FOR PATENT TERM ADJUSTMENT

The PTA procedure begins with a computer-generated calculation performed by the PTO based on information recorded in the PTO's automated Patent Application Information Retrieval (PAIR) database. PTA is calculated twice for all patent applications in this manner: once when the PTO mails the Notice of Allowance and again when the PTO mails the notification of patent issuance. Thus, all allowed patent applications are eligible for PTA. The result of the initial PTA calculation will be reflected in the Notice of Allowance, even if the PTA determination at that time is an adjustment of zero days.

A. Calculation of Patent Term Adjustment

Auditing the PTO's calculation of PTA can be complicated and requires consideration of numerous actions (and inactions) caused by the PTO and the applicant over the course of prosecution of the application from the date of filing to the mailing date of the Notice of Allowance, and again up to the date of issuance. If the notice of allowance of an application indicates a PTA differing from that calculated by the applicant, the applicant can request reconsideration of the PTA (see, 37 C.F.R. § 1.705(b)) no later than payment of the issue fee.

After the patent issues, the applicant again has an opportunity to dispute the PTA calculation by the PTO. If the PTA is shorter than that to which the applicant believes he or she is entitled, the applicant can file a request for reconsideration of the PTA within two months of the date the patent issues. See, 37 C.F.R. § 1.705(d). However, any request for reconsideration that raises issues that were raised, or could have been raised, under 37 C.F.R. § 1.705(b) based on a PTA indicated in the Notice of Allowance will be dismissed as untimely as to those issues.

III. DETERMINING WHEN A PATENT IS ELIGIBLE FOR PATENT TERM EXTENSION

The patent term extension (PTE) doctrine comes from Title II of the Drug Price Competition and Patent Term Restoration Act of 1984 (“Hatch-Waxman”). See, 35 U.S.C. §156. The purpose of Hatch-Waxman is to encourage new drug research by compensating for reductions in patent term arising from the requirement that certain drug products must first obtain federal regulatory approval before they can be marketed in the United States. For instance, for a new human drug, the Federal Food, Drug and Cosmetic Act (FDCA) requires extensive testing in both animals and humans to demonstrate that a new drug is safe and effective before it may be marketed. This testing and approval process can take many years. Prior to Hatch-Waxman, effective patent protection was often far shorter than its statutory entitlement because drug products are frequently patented before the required FDA approval can be obtained. Consequently, the 20-year clock could start ticking years before a drug product reaches the market, thereby shortening the length of time the patent could be used to exclude others from commercializing (i.e., making, using, selling, offering to sell, or importing into the United States) the same drug product.

With the advent of Hatch-Waxman, part of the time spent seeking regulatory approval may be regained by lengthening the patent term of an eligible patent in order to compensate for this type of delay. Under Hatch-Waxman, PTE is available to eligible patents that cover human drug products, veterinary drug products and medical devices. The rules for determining eligibility for PTE for drug products apply to patents that claim a drug product. Both the PTO and FDA participate in calculating and determining PTEs, but it is the PTO that makes the final determination on patent eligibility. After an applicant files a request for PTE, the PTO notifies the FDA of the filing, after which the FDA reviews the application, determines the applicable regulatory review period and notifies the PTO accordingly. Subsequent determination of the PTE is made by the PTO solely on the basis of the representations contained in the application for the extension. No third-party communications will be considered by the PTO outside an “extraordinary situation, when justice requires”.

The maximum term extension is five (5) years, provided that the extension does not result in a total remaining patent term of more than fourteen (14) years. This 14-year period is measured from the date the drug product received regulatory approval up to the date of patent expiration (with term extension). Any term extension granted under the statute is applied from the original expiration date of the patent, including any PTA. In cases where a terminal disclaimer has been filed, the extension is measured from the expiration date resulting from the disclaimer, not from the date the patent would have expired in the absence of a terminal disclaimer. Thus, these two provisions for lengthening the term of a patent (PTA and PTE) are calculated independently and run consecutively rather than concurrently.

A patent will only be eligible for extension if it includes at least one claim covering the approved drug product (or its approved method of use or a method of manufacturing it) and satisfies the following five conditions.

1. The patent has not expired;
2. The term of the patent has never been extended;
3. The patent owner or its agent submits a complete and timely application for extension;
4. The product has been subjected to a regulatory review period before its commercial marketing or use; and
5. The permission for the commercial marketing or use is the first permitted, except for patents claiming a method of making a product that primarily uses recombinant DNA technology, for which the permission for commercial marketing or use is the first permitted commercial marketing or use of the product made by the claimed method.

1. Unexpired Patent

The first requirement of the statute is that the application for PTE must be filed before the patent expires. In situations in which a promising drug candidate is covered by a patent, regulatory approval can typically be sought and obtained before the patent expires, provided that the necessary testing demonstrates compliance with the safety and efficacy requirements for new drug applications (NDAs). Alternatively, in situations in which a lead drug is covered by a patent and identified long after the patent issues, the statute allows a patent owner or its agent to apply for PTE early (i.e., before regulatory approval is complete) if the owner or agent reasonably expects the patent to expire before the regulatory review period ends.

2. Term Not Previously Extended

The second requirement of the statute is that the term of an eligible patent may only be extended once. This situation arises where a patent covers more than one drug product that becomes subject to regulatory approval, as in the case of patents claiming generic chemical formulas covering several different compounds having a desirable activity. Although different drug products covered by the patent could be subjected to separate regulatory approval processes and separately marketed, only one term extension is permitted for the patent.

3. Timely Request by Patent Owner or Agent

The third requirement of the statute is that the patent owner or agent must submit a complete and timely application for PTE. A “timely” application must be filed within 60 days from the date the drug product receives approval after the applicable regulatory review period. For human drugs, the 60-day period begins on the date shown on the FDA's approval letter for the drug product. Calculation of this period is critical. For example, if the FDA approval is received on June 30, the application for PTE must be submitted on or before August 29 (unless that date falls on a Saturday, Sunday, or federal holiday, which would extend the deadline until the next business day).

4. Product Subjected to Regulatory Review

The fourth requirement of the statute is that the drug product must have been subjected to a regulatory review period before its commercial marketing or use. The courts have described the regulatory review period as covering the sum of: (i) the testing phase period and (ii) the approval phase period for the drug. For human drug products, the testing phase is measured from the date the investigational new drug (IND) application became effective before the FDA to the date the NDA was filed, and the approval phase is measured from the date the NDA was filed to the date the FDA approved the NDA. The length of PTE generally corresponds to half the number of days in the testing phase plus the total number of days in the approval phase.

Interpretation of the term “product” has also been addressed by the courts and has been held, in the case of drug products, to refer to the active ingredient that was subject to regulatory review and approval. In some instances, the active ingredient has been held to refer to the entire molecule, including any salt or ester of the active moiety; while in other cases, active ingredient has been interpreted as having a narrower meaning, limited to the active moiety itself and not including its salt or ester forms. In either case, it is well established that the regulatory review period for an FDA-approved product cannot serve as a basis for PTE if an earlier product containing the same active ingredient was previously approved by the FDA.

It is important to note that drug manufacturers should be mindful of which drugs to focus on for FDA approval and which patents to extend by PTE because prior approval of a different drug containing the same active ingredient (e.g., a different dosage strength, form, or formulation) will limit the availability of PTE to the patent covering the first approved drug product only. Additionally, only one patent may be extended based on the regulatory review period for the active ingredient. Thus, even if multiple patents cover various aspects of the drug product that is the subject of regulatory approval (e.g., one patent claims the approved method of use, and another claims a composition containing the approved product) only one patent would be extendible. Nevertheless, this section of the statute does not limit a patentee to submitting only one application for extension. Because there is no guarantee that the one submitted will be granted, it is permissible to file more than one application for PTE on the basis of the same regulatory review period. If more than one patent is deemed eligible for extension, the applicant will be given an opportunity to elect which one to extend.

5. First Commercial Marketing or Use

The fifth requirement of the statute is that the regulatory approval of the drug product must have been the first permitted commercial marketing or use of that product. In other words, the regulatory approval of the active ingredient that is the subject of the PTE must mark the first time that the active ingredient has been approved, either alone or in combination, for marketing and use in the United States. For example, if an active ingredient has been previously approved for Indication A, a patent covering the use of that same active ingredient for a new Indication B would not be eligible for PTE, despite delays in the regulatory review associated with the approval of new Indication B, because the owner of the drug product had already received permission to commercially market or use this active ingredient. Note, an expanded discussion of these issues is found in Appendix A.

Hatch-Waxman also requires that the regulatory approval at issue must have been for the first commercial marketing or use of the “product”, which is expressly defined by Hatch-Waxman as “the active ingredient of a new drug, including any salt or ester of the active ingredient.”

Drug companies should also be aware that if a parent compound has been approved, PTE will not be available for patents covering new uses of that parent compound or its salt or ester forms even ,if the approved indication is wholly-unrelated to an ongoing research and development. Similarly, development of combination therapies should be conducted with consideration of prior FDA approvals relating to each active ingredient in the combination. Unless at least one of the active ingredients will be new to the marketplace, PTE will not likely be available for a patent covering the combination, regardless of whether the combination exhibits synergistic effects.

A. Due Diligence

The PTE doctrine is not designed to provide blanket compensation for the entire period of regulatory review of a product. The applicant for PTE must demonstrate that it exercised due diligence during the review period. Through this requirement, Hatch-Waxman provides an incentive for drug manufacturers to take an active role in pursuing regulatory approval once an IND application is made effective by the FDA in order to maximize the available extension period.

After the FDA calculates the length of the regulatory review period and publishes its determination in the Federal Register, there follows a 180-day period during which any person may file a due diligence petition to challenge the FDA's determination-for example, by alleging that the PTE applicant did not act with due diligence during the regulatory review period. The FDA will then review the petition and the regulatory review period to decide whether or not the applicant did indeed act with due diligence.

To assess an applicant's due diligence, the FDA examines “[t]he facts and circumstances of the applicant's actions during the regulatory review period to determine whether the applicant exhibited that degree of attention, continuous directed effort, and timeliness as may reasonably be expected from, and are ordinarily exercised by, a person during a regulatory review period.” The FDA will consider all relevant factors, such as the amount of time between the approval of an investigational exemption or research permit and the commencement of a clinical investigation and the amount of time required to conduct a clinical investigation. Investigational exemptions, for example, include clinical investigations that are not intended to be reported to the FDA as well-controlled studies in support of a new use or a significant change in the drug labeling.

In some instances, the entity engaged in the regulatory review process is not the patentee. In this context, the marketing entity pursuing FDA approval is deemed to be the agent of the patentee applying for PTE, and the activities of the marketing entity become relevant in determining due diligence for purposes of calculating PTE. This agency relationship also arises with respect to requests for interim extensions, which may be filed if the owner of record of the patent or its agent reasonably expects that the applicable regulatory review period could extend beyond the expiration of the patent term. Hence, the statute recognizes that the patent owner may not have access to all the information on which to base a reasonable expectation concerning the duration of regulatory review and that such information would be provided by the marketing entity as agent of the patent owner. In situations in which the patent owner has not obtained the necessary information from the marketing entity to adequately describe premarket activities, establish diligence, or otherwise comply with the statutory requirements, it has been suggested that the PTE applicant would not be entitled to PTE.

IV. PROCEDURE FOR REQUESTING PATENT TERM EXTENSION

A. Formal Requirements

An application for PTE must include the relevant basic information regarding the patent and the drug product. For instance, the application must specify the complete identity of the approved drug product (e.g., chemical name, generic name, structural formula, and physical characteristics, such as molecular weight, etc.). The PTE application must also identify the applicable law governing the regulatory review period (e.g., for human drug products, the applicable law is FDCA § 505(b) - which is codified at 21 U.S.C. § 355(b)), and the date the drug product received FDA approval.

In addition to these initial formalities, the PTE application must also include a statement that at least one claim in the patent covers the approved product or a method of using or making the approved product. Thus, some level of claim construction is normally required in order to support this statement and provide the requisite showing that at least one claim reads on the relevant subject matter. For example, when the approved drug product is a salt and the patent claims broadly cover numerous compounds and their salt forms, the statement should describe how the individual approved product specifically falls within the scope of the claims.

The PTE application further requires a complete statement of the relevant dates and information needed to enable the FDA to determine the applicable regulatory review period, including information regarding significant activities (e.g., IND inactivation periods) that took place during the testing and approval phases. Additionally, the PTE application must include a calculation of the length of the extension requested, including a description of how the calculation was made.

Decisions on PTE can take upwards of two years. Given this time frame, the patent term might expire before a decision is reached. In this situation, the applicant is permitted to file for an interim extension, preferably at least three months prior to the patent expiration date The requirements for requesting an interim extension are the same as those required for a formal PTE application. Further, the PTO may issue an interim extension on its own while the decision on PTE is pending. More than one interim extension may be granted, for periods of up to one year each, until the PTO issues a Notice of Final Determination. However, the interim extension period cannot last longer than the period of extension to which the patent would theoretically be eligible.

Once an extension is granted, the extension period is made known to the public by issuance of a certificate of extension that states the number of days by which the term is extended. The certificate of extension is recorded in the patent file history and is considered a part of the original patent.

B. Calculation of Patent Term Extension

Calculation of a PTE is fairly complicated. The pertinent rules are detailed and rely on the relevant dates related to the applicant's actions, inactions, and overall diligence during the regulatory review period (i.e., the testing and approval phases). While the calculation requires a number of variables which were do not, as yet, possess, I have generated one possible hypothetical scenario follows:

Company X identifies Drug X as a potentially useful treatment for lung cancer based on initial laboratory research and testing. Company X then files a patent application covering a method of treating that disease by administering Drug X, and begins the testing phase in order to obtain FDA approval of Drug X for the aforementioned indication. The relevant dates are as follows:
June 1, 1992: Company X files a patent application related to Drug X.

October 10, 1994: Company X files an IND application.
November 10, 1994: The IND becomes effective, beginning the testing phase period. Company X acts with due diligence during the entire testing phase period.
January 5, 1995: Company X's patent issues with claims directed to a method of treating lung cancer by administering Drug X, with an original patent expiration date of June 1, 2012.
March 12, 1999: Company X files an NDA, simultaneously ending the testing phase period (1583 days) and beginning the approval phase period. Company X acts with due diligence during the entire approval phase period.
July 5, 2001: FDA approves the NDA, ending the approval phase period (846 days).

Based upon the aforementioned dates and information, Company X's patent is entitled to a PTE of 1,129 days (i. e., just over three years). For a major pharmaceutical product, an extra three (3) years of patent protection could be worth billions of dollars to Company X. The extension period for Company X's patent was calculated using the PTE calculation steps shown below:
Line 1: Enter date for testing phase as defined in 37 CFR § 1.775(c)(1) 1,583 days
Line 2: Enter date for approval phase as defined in 37 CFR. § 1.775(c)(2) 846 days
Line 3: Add Line 1 and Line 2 and enter total here 2,429
Line 4: Enter the number of days of the period of Line 2 which
occurred prior to the issue date of the patent 0 days
Line 5: Enter the number of days of the period of Line 2 during
which the Applicant failed to act with due diligence as defined in
37 CFR § 1.775(d)(1)(ii) 0 days
Line 6: Add Line 4 and Line 5 and enter total here 0
Line 7: Subtract Line 6 from Line 3 and enter the difference
here (if less than zero, enter 0) 0
Line 8: Enter the number of days of the period of Line 1 which
occurred prior to the issue date of the patent 56 days
Line 9: Enter the number of days of the period of Line 1 during
which the Applicant failed to act with due diligence as defined in
37 CFR § 1.775(d)(1)(ii) 0 days
Line 10: Add Line 8 and Line 9 and enter total here 56
Line 11: Subtract Line 10 from Line 7 and enter the difference here 2,373
Line 12: Enter the number of days from Line 1 here 1,583 days
Line 13: Enter the number of days from Line 10 here 56 days
Line 14: Subtract Line 13 from Line 12 and enter the difference
here (if less than zero, enter 0) 1,527
Line 15: Multiply Line 14 by 0.5 and enter the amount here 763
Line 16: Subtract Line 15 from Line 11 and enter the difference
here (if less than zero, enter 0) 1,610
Line 17: Enter the original expiration date of the patent here 06/01/2012
Line 18: Enter the expiration date of the patent if extended by
the number of days on Line 16 here 10/28/2016
Line 19: Enter the date of the final FDA approval here 07/05/2001
Line 20: Limitation set forth in 37 CFR § 1.775(d)(3) 14 years
Line 21: Add the number of years on Line 20 to the date on
Line 19 and enter the revised date here 07/05/2015
Line 22: Enter the earlier date appearing on Line 18 or Line 21 07/05/2015
Line 23: Enter the original expiration date of the patent from
Line 17 here 06/01/2012
Line 24: Select one of the following three (3) scenarios and
enter the listed time period here 5 years

(i) The patent issued after 09/24/84 5 years
(ii) The patent issued prior to 09/24/84 and no request for
Exemption (as defined in 37 CFR § 1.775(d)(6)(ii)) was filed
prior to 09/24/84 5 years
(iii) The patent issued prior to 09/24/84 and a request for
Exemption (as defined in 37 CFR § 1.775(d)(6)(ii))
was filed prior to 09/24/84 2 years

Line 25: Add the number of year on Line 24 to the date on
Line 23 and enter the revised date here 06/01/2017
Line 26: Enter the earlier date appearing on Line 22 on
Line 25 here 07/05/2015
Line 27: Enter the original expiration date of the patent from
Line 17 here 06/01/2012
Line 28: Enter the number of days by which Line 26 and
Line 27 differ here. This is the length of the patent term extension. 1,129 days

V. ORANGE BOOK LISTING

Considerations for determining whether a patent is capable of being listed in the Orange Book, are also relevant to determinations of PTE eligibility. The deadline for deciding whether to list a patent in the Orange Book falls at approximately the same time as the deadline for deciding whether to file for PTE. That is, the NDA holder must submit the patent to the FDA for listing in the Orange Book within thirty (30) days after the FDA approves the drug product; and the patentee must file the PTE application within sixty (60) days after the FDA approval date. Thus, it is important for both the NDA holder and the patentee to be aware of the FDA's approval process in order to maximize the period of commercial viability of the patent.

VI. SCOPE OF PATENT CLAIMS ENTITLED TO EXTENSION

As previously discussed in Section III(5), regulatory approval of the drug product must have been the first permitted commercial marketing or use of that product. In other words, the regulatory approval of the active ingredient that is the subject of the PTE must mark the first time that the active ingredient has been approved, either alone or in combination, for marketing and use in the United States. For example, if an active ingredient has been previously approved for Indication A, a patent covering the use of that same active ingredient for a new Indication B would not be eligible for PTE, despite delays in the regulatory review associated with the approval of new Indication B, because the owner of the drug product had already received permission to commercially market or use this active ingredient.

Specific examples of such situations have been addressed by the courts. For instance, in the Fisons¹case, Fisons held three patents that covered three different forms of a drug (i.e., a nebulizer solution, an aqueous solution, and an inhaler), all of which contained the same active ingredient, cromolyn sodium. For each of the three drug products, Fisons sequentially performed the necessary testing, obtained FDA approval, and applied for PTE of the corresponding patent.² In each case, Fisons's application for extension was denied in view of a prior FDA approval of cromolyn sodium inhalation capsules in 1973.³ Although Fisons argued that the previously approved product was different from each of Fisons's later-approved products, the Federal Circuit held that Hatch-Waxman defines the term “product” as meaning “human drug product,” which is further defined as “the active ingredient of a new drug.”⁴ Thus, the prior regulatory review and 1973 FDA approval of cromolyn sodium foreclosed PTE for all patents covering later-approved products containing the same active ingredient, despite their different dosage forms. For PTE purposes, the only relevant regulatory review period for cromolyn sodium ended in 1973, and Fisons's later review periods did not confer PTE eligibility on its patents.

Hatch-Waxman also requires that the regulatory approval at issue must have been for the first commercial marketing or use of the “product, which, as noted above, is expressly defined as “[t]he active ingredient of a new drug…including any salt or ester of the active ingredient.” ⁵

In another relevant case, Glaxo v. Quigg, the Federal Circuit interpreted “active ingredient” as referring to the entire active molecule, including its salt or ester portion. Glaxo had developed and obtained FDA approval of cefuroxime axetil (Ceftin), an ester of cefuroxime, which is an organic acid.⁶ Prior to approving the cefuroxime ester in 1987, the FDA had granted approvals for two cefuroxime salts (Zinacef and Kefurox) in 1983 and 1986, respectively.⁷ The parent compound itself (i.e., the active moiety, cefuroxime) had never been approved by the FDA. The PTO argued that Glaxo's request for extension of the Ceftin patent had been duly denied because cefuroxime was the active moiety of both the previously approved cefuroxime salts and Glaxo's cefuroxime axetil ester.⁸

The court disagreed, however, and found that the relevant “drug product” was cefuroxime axetil.⁹ Next, the court considered whether cefuroxime axetil or a salt or ester of cefuroxime axetil had previously received regulatory approval, and concluded that no such approval had been granted.¹⁰ Rather, the only previously approved products were salts of cefuroxime acid (which was not FDA-approved). Consequently, the court determined that the prior approval of cefuroxime salts did not preclude Glaxo's PTE request.¹¹ The court further concluded that the Ceftin patent satisfied the first commercial marketing requirement and was eligible for PTE.¹²

In a later case, the Federal Circuit addressed a different but related inquiry in Pfizer v. Dr. Reddy's Labs, in which the court equated “active ingredient” with “active moiety.”¹³ In Pfizer, the Federal Circuit considered the scope of the PTE rather than the outright eligibility for PTE, in the context of enforcement of a patent with an extended term.¹⁴ In this case, Pfizer asserted a patent having product claims covering both amlodipine and its besylate and maleate salt forms.¹⁵ Amlodipine besylate had been approved by the FDA, after which Pfizer obtained a PTE based on a PTE application that identified the besylate salt (Norvasc) as the product for which regulatory approval had been obtained.¹⁶

According to the Pfizer court, the rights derived from Pfizer's PTE were not limited to Norvasc. Rather, these rights extended to all the claimed forms of amlodipine, including its salts and esters, even though only the besylate salt form had been previously approved by the FDA.¹⁷ Accordingly, the court held that Dr. Reddy's proposed marketing of amlodipine maleate would infringe Pfizer's patent because claims covering this salt form would remain in force for the duration of the PTE period.¹⁸

This decision is significant because the court in Pfizer appears to have arrived at its conclusion based on its adoption of a 1994 FDA position that the term “active ingredient,” as it is used in the context of the PTE rules, means “active moiety”.¹⁹ Thus, the court allowed for an alternative interpretation of the term “active ingredient” under the PTE rules. Consequently, this decision can be considered to impact the meaning of the term “product” in § 156 because, under Pfizer, “product” more broadly refers to the active moiety of an FDA-approved drug product. A determination of PTE eligibility then turns on whether any compound incorporating the active moiety, or a salt or ester of the active moiety, had previously received regulatory approval. Under the Pfizer ruling, a denial of PTE eligibility would be expected in a situation where the active moiety of the product had been previously approved by the FDA.

In a more recent proceeding,²⁰ the PTO issued a final decision denying a PTE request for AstraZeneca's patent covering Nexium IV (esomeprazole sodium for injection). In explaining its initial rationale for the denial, the PTO stated that the 1990 Glaxo decision was impliedly over-ruled by the decision in Pfizer.²¹ Consequently, the PTO ignored the Glaxo holding that the first marketing requirement does not preclude PTE for a patented compound that is not a salt or ester of a previously approved product.²² The PTO later recanted this statement, but nevertheless maintained that Glaxo was distinguished from the present facts even though it remained binding precedent.²³ The PTO thus denied the PTE request related to Nexium IV in view of the prior regulatory approval of Nexium, another salt form of esomeprazole, and confirmed that “extension based upon subsequent approvals of other compounds with the same active moiety must be barred.”²⁴

Another area of increasing interest relates to combination therapies. Here, the primary issue is whether PTE is available for patents covering products that contain combinations of active ingredients, particularly where one or more of the active ingredients has previously received regulatory approval.²⁵ In Arnold Partnership v. Dudas,²⁶ the patent at issue claimed a drug product that contained a combination of two active ingredients, hydrocodone and ibuprofen, each of which had been previously approved by the FDA.²⁷

The Arnold Partnership patent claimed hydrocodone and ibuprofen as a synergistic combination, which required its own premarketing regulatory review and approval because each component had only been available separately. Arnold Partnership argued that the patent claiming the hydrocodone/ibuprofen product should be extended because this was a new combination therapy that had not been previously approved. However, the court disagreed, interpreting the term “drug product” in § 156(f) as referring to an individual active ingredient. The court went on to state that “[t]he drug product may consist of either a single active ingredient or an active ingredient in combination with another active ingredient.”²⁸ For clarification, the court provided an example, stating: "[t]o extend the term of a patent claiming a composition comprising A and B, either A or B must not have been previously marketed.²⁹ In other words, at least one of the claimed active ingredients must be new to the marketplace as a drug product.³⁰

In dicta, the Arnold Partnership court further commented on the potential impact of a synergistic combination of active ingredients, stating that it “…doubts that synergistic effects are an appropriate distinction for term extension policies, particularly where the statutory language does not distinguish at all between synergistic and nonsynergistic combination”.³¹

VII. PTE AND NON-FDA APPROVED USE

First, as previously stated in Section III(4), it is important to note that drug manufacturers should be cognizant of which drugs to focus on for FDA approval and which patents to extend by PTE because prior approval of a different drug containing the same active ingredient (e.g., a different dosage strength, form, or formulation) will limit the availability of PTE to the patent covering the first approved drug product only. Additionally, only one patent may be extended based on the regulatory review period for the active ingredient.³² Thus, even if multiple patents cover various aspects of the drug product that is the subject of regulatory approval (e.g., one patent claims the approved method of use, and another claims a composition containing the approved product) only one patent would be extendible. Nevertheless, this section of the statute does not limit a patentee to submitting only one application for extension. Because there is no guarantee that the one submitted will be granted, it is permissible to file more than one application for PTE on the basis of the same regulatory review period. If more than one patent is deemed eligible for extension, the applicant will be given an opportunity to elect which one to extend.

With respect to claim scope, the scope of rights derived from PTE includes any approved use of the product (for patents with product claims), any approved method of using the product (for patents with method of use claims), or any method of making the approved product (for patents with method of manufacturing claims).³³

For example, in the case of Pfizer v. Dr. Reddy's Labs.,³⁴ the Federal Circuit held that the PTE provided term extension as to both the besylate and maleate salt forms (as they were taught in the claims), despite the fact that only the besylate salt (Norvasc) had been previously approved by the FDA. The scope of the patent term extension was not limited to the scope of FDA approval. Rather, the court held that the rights derived from the PTE extended to all the claimed forms of amlodipine, the “drug product,” including its salts and ester.”³⁵

However, in contrast, where the scope of the claims is more limited, the scope of the extension will be more limited as well. For instance, if PTE had been granted in the Nexium IV case³⁶, the scope of the extension would only have covered esomeprazole sodium salt for parenteral administration because this is the scope of the patent claims. Therefore, in this case, the scope of the extension would be limited to the subject of the regulatory review process that formed the basis of the PTE application (i.e., esomeprazole sodium for injection).

VIII. SUPPLEMENTARY PROTECTION CERTIFICATE (SPC) IN THE EU

In European Union member countries, a supplementary protection certificate (SPC) is a sui generis extension of a patent under a specific set of rights. SPC is available for medicinal products (e.g., drugs) and plant protection products (e.g., insecticides and herbicides). Supplementary protection certificates were introduced to compensate for the long period of time needed to obtain regulatory approval of these products (i.e., authorization to put these products on the market)³⁷ and to remedy the disparities and shortcomings in national patenting systems for pharmaceutical research. It aims in particular to guarantee sufficient protection for the development of medicinal products in the European Union (EU).

The certificate is issued if the product for which it was requested, as a medicinal product and at the time when the application was filed in a Member State, meets the following four (4) conditions:
1) the product is protected by a basic patent in force;
2) the product, as a medicinal product, has been granted a marketing authorization;
3) the product has not already been the subject of a certificate; and
4) the marketing authorization is the first authorization to place the product on the market as a medicinal product.

Furthermore, the certificate applies to the product in the same way as the patent from which it benefits. The Regulation also specifies the arrangements relating to application for and granting of the certificate and likewise the conditions for lapse, invalidity and publicity of the certificate.

A supplementary protection certificate comes into force only after the corresponding general patent expires. The SPC normally has a maximum life time of five (5) years, although it may be extended to 5.5 years when the SPC relates to a human medicinal product for which data from clinical trials conducted in accordance with an approved Pediatric Investigation Plan (PIP) have been submitted, as set forth in Article 36 of Regulation (EEC)

No 1901/2006. The total combined duration of market exclusivity of a patent and SPC can not normally exceed 15 years. However, the grant of an additional 6-month SPC extension for the submission of data from an approved (pediatric use) PIP can extend this combined duration to at least 15.5 years. In addition, it is yet to be judicially-clarified whether more than 15.5 years can be obtained in some limited circumstances. While this PIP-based extension mechanism extends the total term of a patent, it does so under a somewhat different set of rights than the SPC.
Supplementary protection certificates in the European Union are based primarily upon two regulations. Although all countries in the EU are required to provide supplementary protection certificates, no unified cross-recognition exists. Thus, applications must be filed and approved on a country-by-country basis.

A. Determination of Patent Term

The term of an SPC depends upon the date of issuance of the first Marketing Authorization (MA) within the European Economic Area (EEA)³⁸ and can be determined by the following equation:

Term = ([date of 1st MA in the EEA] - [date of filing of corresponding patent]) - 5 years

Under normal circumstances, this means the following:

• No SPC term is available if less than 5 years have elapsed between the date of filing of the corresponding patent and the date of issuance of the first MA in the EEA.
• If the first MA is issued more than five years but less than ten years after the filing date of the corresponding patent, an SPC is granted for a term corresponding to the period elapsed between the five-year point and the MA issuance date.
• If the first MA is issued more than ten years after the filing date of the corresponding patent, an SPC is granted for a five-year term.

A MA in Switzerland was also considered as being a first MA for the calculation of the SPC duration, even though Switzerland is not part of the EEA. This is because such a MA was automatically effective in Liechtenstein, which has been a member of the EEA since May 1, 1995. This was decided by the European Court of Justice (ECJ) in the joined cases of Novartis et al. v. Comptroller-General³⁹ and Ministère de l'Economie v. Millennium Pharmaceuticals.⁴⁰ However, as answer to the decision of the ECJ, the contract between Switzerland and Liechtenstein was amended. Since July 1 2005 the automatic effect of a Swiss MA in Liechtenstein is abolished. The recognition is now delayed by a time period, which is normally 12 months.

Article 36 of Regulation 1901/2006 provides for a 6-month extension to SPC term. The extension is available only under certain conditions, the most notable being the requirement for the submission of a new MA application containing data from all trials conducted in accordance with an approved Pediatric Investigation Plan (PIP). Consequences of the introduction of the 6-month SPC extension include:

• the maximum term of an SPC can now be up to 5.5 years; and
• the maximum duration of market exclusivity (patent + SPC) can now be up to at least 15.5 years.

The rewards provided in Regulation 1901/2006 (including the 6-month SPC extension) are intended to compensate pharmaceutical companies for the substantial costs of conducting clinical trials in the pediatric population. This is in contrast to the legislative intent of the original SPC system (as set out in Council Regulation (EEC) No 1768/92), which was to compensate pharmaceutical companies for the loss of exclusivity caused by regulatory delays. Thus, the reasons for the introduction of the 6-month SPC extension are thus independent of the SPC system. Because of this, an issue arises in relation to whether the 6-month extension can be obtained even in circumstances where no SPC term would be available without the extension. This issue has not yet been answered by a European national court (or the European Court of Justice). Unfortunately, due to a number of differing opinions and models, it seems that this issue can only be resolved by a reference to the European Court of Justice.

B. Scope of Protection

According to Article 4 of Council Regulation No 1768/92, the scope of an SPC extends "…only to the product covered by the authorization to place the corresponding medicinal product on the market and for any use of the product as a medicinal product that has been authorized before the expiry of the certificate". The European Court of Justice has decided, however, that the scope of an SPC is sometimes capable of encompassing more than just the single form of the active ingredient that is included in the medicinal product authorized for sale. In accord, in case C-392/97⁴¹, the European Court of Justice held that: "where an active ingredient in the form of a salt is referred to in the marketing authorisation concerned and is protected by a basic patent in force, the certificate is capable of covering the active ingredient as such and also its various derived forms such as salts and esters, as medicinal products, in so far as they are covered by the protection of the basic patent".

C. Legal Basis of Protection

Supplementary protection certificates in the European Union are based primarily upon two regulations:

• Council Regulation (EEC) No 1768/92 of June 18, 1992, concerning the creation of a supplementary protection certificate for medicinal products⁴² which entered into force on January 2, 1993.
• Regulation (EC) No 1610/96 of the European Parliament and of the Council of July 23, 1996, concerning the creation of a supplementary protection certificate for plant protection products⁴³ which entered into force on February 8, 1997.

Supplementary protection certificates may come into effect at the expiry of a national or European patent. However, the European Patent Convention (EPC) needed to be modified to allow such "extension" of the term of European patent. In accord, Article 63 of the EPC was modified on December 17, 1991 to specify to, although European patents have a term of 20 years as from the date of filing of the application (Art. 63(1)), “…nothing shall limit the right of a Contracting State to extend the term of a European patent, or to grant corresponding protection which follows immediately on expiry of the term of the patent, under the same conditions as those applying to national patents…if the subject-matter of the European patent is a product or a process of manufacturing a product or a use of a product which has to undergo an administrative authorization procedure required by law before it can be put on the market in that State.”⁴⁴

The pediatric extension of Supplementary Protection Certificates is based primarily upon the following Regulations:⁴⁵

• Regulation 1901/2006 of 12 December 2006 on medicinal products for pediatric use and amending Regulation 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004.
• Regulation 1902/2006 of 20 December 2006 amending Regulation 1901/2006 on medicinal products for pediatric use.

D. Fees

The level of the fees is that applying on the date the certificate is due to take effect or, if paid earlier, the actual date of payment. Currently the fees for five (5) successive years are £600, £700, £800, £900 and £1000.

E. Review

An excellent review of the EU supplementary protection certificate procedure can be found at: http://smtp1.patent.gov.uk/spctext.pdf.

IX. PATENT TERM EXTENSION IN JAPAN

Patent term extension is available in Japan, although information concerning the process is rather scarce and difficult to interpret.

In brief, Japan appears to have harmonized the major components of its patent term extensions with those of the U.S. and EU. The maximum term of extension is five (5) years⁴⁶ and there is no mechanism for any additional extension period (e.g., the 6 month pediatric extension in the EU). Interestingly, Japan is the only country that has a minimum time of patent term extension, which requires that the extension be at least two (2) years in length.⁴⁷ A recent request for a revision to the patent term extension system has been put forth by the Japan Pharmaceutical Industry Association and the Pharmaceutical Industry Council to abrogate the aforementioned 2-year minimum patent term extension.⁴⁸ The application for patent term extension can not be filed with the Japanese Patent Office (JPO) at anytime after 6 months prior to the expiration of patent rights in Japan.⁴⁹

Endnotes:

¹ Fisons v. Quigg, 876 F.2d 99, 100 (Fed. Cir. 1989).
² Fisons v. Quigg, 8 U.S.P.Q.2d 1491, 1492 (D.D.C. 1988).
³ Id.
⁴ Fisons, 876 F.2d at 100; 35 U.S.2 Id. at 400.
⁵ 35 U.S.C. § 156(f)(2).
⁶ Galaxo Operations UK Ltd. v. Quigg, 894 F.2d 392, 394 (Fed. Cir. 1990).
⁷ Id. at 393.
⁸ Id. at 400.
⁹ Id. at 394.
¹⁰ Id.
¹¹ Id. at 396.
¹² Id. at 400.
¹³ Pfizer v. Dr. Reddy’s Laboratories, 359 F.3d 1361, 1366 (Fed. Cir. 2004).
¹⁴ Id. at 1361.
¹⁵ Id. at 1361-1364.
¹⁶ Id. at 1364.
¹⁷ Id. at 1366; 35 U.S.C. § 156(f).
¹⁸ Pfizer, 359 F.3d at 1366-1367.
¹⁹ Id. at 1366. See also, ANDA Regulations: Patent and Exclusivity Provisions, 59 Fed. Reg. 50338, 50358 (October 3, 1994).
²⁰ In re Patent Term Extension Application for U.S. Patent No. 6,143,771, Notice of Final Determination (July 28, 2005), available at www.uspto.gov/go/foia/comm/pte/614377lne.pdf
[hereinafter ‘771 Final Determination]. The denial was based on the previous approval and commercial marketing of Nexium (esomeprazole magnesium).
²¹ Pfizer, 359 F.3d 1361.
²² ‘771 Final Determination, supra note 78, at 3.
²³ Decision Denying Application for Patent Term Extension for U.S. Patent No. 6,143,771 (September 12, 2007).
²⁴ ‘771 Final Determination, supra note 78, at 3.
²⁵ Id.
²⁶ Arnold Partnership v. Dudas, 362 F.3d 1338, 1341 (Fed. Cir. 2004).
²⁷ Id. at 1339.
²⁸ Arnold Partnership, 362 F.3d at 1341.
²⁹ Id.
³⁰ Id. at 1343.
³¹ Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392, 396 (Fed. Cir. 1990).
³² Fisons v. Quigg, 876 F.2d 99, 101 (Fed. Cir. 1989); 35 U.S.C. § 156(c)(4) (“[i]n no event shall more than one patent be extended…for the same regulatory review period for one product”).
³³ 35 U.S.C. § 156(b)(1)-(3).
³⁴ Pfizer v. Dr. Reddy's Laboratories, Inc. 359 F.3d 1361, 1367 (Fed. Cir. 2004).
³⁵ Id. at 1366; 35 U.S.C. § 156(f).
³⁶ In re Patent Term Extension Application for U.S. Patent No. 6,143,771, Notice of Final Determination (July 28, 2005).
³⁷ “Whereas at the moment the period that elapses between the filing of an application for a patent for a new medicinal product and authorization to place the medicinal product on the market makes the period of effective protection under the patent insufficient to cover the investment put into the research ..." in Council Regulation (EEC) No. 1768/92 of June 18, 1992 concerning the creation of a supplementary protection certificate for medicinal products.
³⁸ The European Economic Area (EEA) was established on January 1, 1994 following an agreement between member states of the European Free Trade Association (EFTA), the European Community (EC), and all member states of the European Union (EU). It allows these EFTA countries to participate in the European single market without joining the EU.
³⁹ Case C-207/03
⁴⁰ Case C-252/03; see, also: Snodin and Miles, RAJ Pharma 18(7):459 (2007).
⁴¹ Farmilitalia Carlo Erba Srl’s SPC Application (Case C-392/97).
⁴² Council Regulation (EEC) No. 1768/92 of June 18, 1992 concerning the creation of a supplementary protection certificate for medicinal products.
⁴³ Regulation (EC) No. 1610/96 of the European Parliament and of the Council of July 23, 996 concerning the creation of a supplemental protection certificate for plant protection products.
⁴⁴ Article 63 EPC.
⁴⁵ Regulation (EC) No. 1901/2006 of the European Parliament and of the Council of December 12, 2006 on medicinal products for pediatric use and amending Regulation (EEC) No. 1768/92, Directive 2001/20EC, Directive 2001/83/EC and regulation (EC) No. 726/2004.
⁴⁶ Section 67(1) of the Patent Law.
⁴⁷ Section 67(2) of the Patent Law.
⁴⁸ Section 67bis (3) of the Patent Law.
⁴⁹ Id.