UNITED STATES PATENT AND TRADEMARK OFFICE

DEC 20 201i
InRe: Thomas G. Rowan
JONES DAY
222 East 41 st St.
New York, NY 10017
An application for extension of the patent term of U.S. Patent No. RE38115 (the '115 patent) under
35 U.S.C. 156 was filed in the United States Patent and Trademark Office (USPTO) on December
17,2010. The application was fied by Center for Neurologic Study (Applicant) the owner of
record of the patent. Extension was sought based upon the premarket review under 505 of the
Federal Food, Drug, and Cosmetic Act (FFDCA) of a human drug product known by the tradename
NEUDEXTA( and having the active ingredients dextromethorphanhydrobromide and quinidine
sulfate. The application indicated that NUEDEXT A( (dextromethorphan hydro bromide and
quinidine sulfate) had been approved for commercial use and sale by the Food and Drug
Administration (FDA) on October 29,2010.
On May 31,2011 (correcting the March 29,2011 USPTO letter to FDA), the USPTO sent a letter to
the FDA stating, "Our review ofthe application to date indicates that the subject patent would NOT
be eligible for extension of the patent term under 156." In the March 29, 2011 letter, the USPTO
indicated that the' 115 patent would not be eligible for extension based on the regulatory review of
NEUDEXTA because both active ingredients, i.e., dextromethorphan hydrobromide and quinidine
sulfate, were previQusly approved under section 505 of the Federal Food, Drug and Cosmetic Act
(FFDCA). The USPTO requested the FDA's assistance in determining whether NUEDEXTA(
(dextromethorphan hydrobromide and quinidine sulfate) had been subject to a regulatory review
period in accordance with 156(g) before its first permitted commercial marketing or use in
accordance with section 156(a)(5)(A).
In a letter dated June 9, 2011 from the FDA to the USPTO (FDA letter), the FDA indicated that
NUEDEXTA( (dextromethorphan hydro bromide and quinidine sulfate) had been subject to
regulatory review under new drug application (NDA) 21-879 in accordance with section 505 of the
FFDCA, and confirmed that NDA 21-879 did not represent the first permitted commercial
marketing or use of the active ingredients of NUED EXT A ( (dextromethorphan hydro bromide and
quinidine sulfate). -
A single request for reconsideration of this FINAL DETERMINATION OF INELIGIBILITY may
be made if fied by Applicant within TWO MONTHS of the mailing date of this letter. The period
for response may be extendedpursuant to 37 C.F.R. 1.136. See 37 C.F.R. 1.750. A failure to
respond to this letter wil result in the application papers being placed into the patent file with no
further action taken on the PTE Application.
U.S. Patent No. RE38115
Page 2
A. U.S. Patent No. RE38115 Is Not Eligible for Patent Term Extension
A determination has been made that the '115 patent is NOT eligible for patent term extension under
156 based upon the regulatory review period of NUEDEXT A( (dextromethorphan hydro bromide
and quinidine sulfate).
The FDA offcial records indicate that each of the two active ingredients comprising NUEDEXT A(,
i.e., dextromethorphan hydrobromide and quinidine sulfate, has been previously approved for
commercial marketing or use, prior to the approval ofNUEDEXTA( (dextromethorphan
hydrobromide and quinidine sulfate). In the FDA letter, FDA stated:
A review of the Food and Drug Administration's official records indicates
that this product was subj ect to a regulatory review period. before its commercial
marketing or use, as required under 35 U.S.c. 156(a)(4). However, our records
also indicate that it does not represent the first permitted commercial marketing or
use of the product, as defined under 35 U.S.C. 156()(1). The active ingredients
in NUEDEXTA, dextromethorphan hydrobromide and quinidine sulfate, have been
individually approved previously for commercial marketing or use in several other
approved products including but not limited not to the following:
Active Ingredient Companies Products Application
Numbers
Dextromethorphan Reckitt Benckiser MucinexDM NDA 21-620
Hydrobromide
( dextromethorpha
n hydro bromide
and guaifenisin)
,
"
Multiple (Hi- Dextromethorpha ANDAs 40-027,
Tech Pharma, n Hydrobromide 40-649,88-811,
Vintage, Actavis, in combination 88-762, 88-864,
midAtlantic) with either 90-575
Pseudoephedrine
Hydrochloride or
Promethazine
Hydrochloride
Quinidine Sulfate
Wyeth Pharms,
Quinidex
NDA 12-796
Inc.
u.s. Patent No. RE38115
Page 3,'
"
Multiple (Teva
Quinidine sulfate
ANDAs 40-045,
Pharms,Mutual
81-030-81-031-
Phar, Sandoz,
88-072-83-288-
Watson
85-583
Laboratories
Under 156( a) a term of a patent which claims a product shall be extended if, inter qlia, the
product has been subject to a regulatory review period before its commercial marketing or use.
In addition, 156(a)(5)(A) provides in pertinent part that "the permission for the commercial
marketing or use of the product. . . is the first permitted commercial marketing or use of the
product under the provision of law under which such regulatory review period occurred."
(Emphases added.)
Thus, whether the '115 patent is eligible for patent term extension turns on the requirement in
156(a)(5)(A) that the permission for the commercial marketing or use is the first permitted
commercial marketing or
use of the product.
The term "product"is defined in 156(f) as follows:
(f) For purposes ofthis section:
(1) The term "product" means:
(A) A drug product. . .
(2) The term "drug product" means the active ingredient of-
(A) Anew drug, antibiotic drug, or human biological product . . . .including any
salt or ester of the active ingredient, as a single entity or in combination with
another active ingredient. (Emphasis added.)
By the explicit terms of 156(f)(2), the term "product" as it relates to a human drug product
means the aCtive ingredient of the new drug
product. . See In re Fisons Pharmaceuticals Limited,
231 USPQ 305
(Comrr'rPats.1 986); aftd, Fisons pIc v. Quigg, 8 USPQ2d149t(DDC 1988);
aftd, 10 USPQ2d 1869 (Fed. Cir~ 1988) (holding that the term "product" as used in 156(f)
referst the activeingredient); Glaxo Operations UK
Ltd. v. Quigg, 13 USPQ1628(Fed. Cir.
1990) (holding that the term "product" as used in 156(f) refers to the active ingredient).
Moreover, the issue of compliance with 35 U.S.C. 156(a)(5)(A) was squarely addressed by the
Federal Circuit in Photocurev. Kappos, 603 F.3d 1372 (Fed. Cir. 2010), where
the court relied
on its previous decision in Glaxo v. Quigg, 894 F.2d 392 (Fed. Cir. 1990) (Glaxo IJ),for its .
determination of eligibility of a patent for extension based on the regulatory review of
Photo cure ' s Metvixia product. There the analysis centered around determining what active
ingredient is present in the drug product and whether the permission for commercial marketing or
use of the active ingredient is the first permitted commercial marketing or use.
In addressing compliance with section 156 (a)(5)(A) for a drug product including two active
ingredients, the cour in Arnold P'ship v. Dudas, 362 F.3d 1338, 1341 (Fed. Cir. 2004) held that a
composition comprised of multiple active ingredients is eligible for patent term extension only if
U.S. Patent RE38115
Page 4
at least one of the active ingredients complies with the first commercil marketing requirement of
156(a)(5)(A)). Thus, for regulatory review ofci drug product
with more than one 'active '
ingredient to give rise to eligibility for extension of a patent claiming the drug product,
permission to commercially market and use the product must be the first permitted commercial
marketing or use at least one of the active ingredients. The active ingredients in the
approved
product NUEDEXTACI are dextromethorphan hydrobromide and quinidine sulfate. As noted in
the FDA letter, the active ingredients dextromethorphan hydrobromideand quinidine
sulfate had
each been approved for commercial
marketing and use prior to theapproval ofNUEDEXTA(.
Furthermore, the prior approval of
each of the active ingredients dextromethorphan
hydrobromide and quinidine sulfate by theFDA occurred under
section 505 ofthe FFDCA, the
same provision oflaw under which regulatory review of
the product NUEDEXTA(
(dextromethorphanhydrobromide and quinidine sulfate) occurred. Thus, since neither active
ingredient, dextromethorphan hydro
bromide nor quinidine sulfate, constitute the firstpermitted
commercial marketing or use, the' 115 does not appear to be eligible for extension based on the
regulatory review ofNUEDEXTA(.
Applying the definition of "product" provided in 156(f) to the extension requirement of
156( a)(5)(A), Applicant's product NUEDEXTA( (dextromethorphan hydro
bromide and
quinidine sulfate) does not qualify as the
first permitted marketing or
use of either active
ingredient., Since the approval ofNUEDEXTA( was notthe first permitted marketing or use of
at least one of the active ingredients thereof, dextromethorphan hydrobromide or quinidine
sulfate, the patent is not eligible for patent term extension based upon the regulatory review of
NUEDEXTA(.
The Applicant for patent term extension has argued in their application that the '115 patent i~
entitled to an extension under 156 because section 505 of
the FFDCA asarrended by the Drug
Price Competition and Patent Term Restoration Act of 1984 constitutes a different "provision of
law" as that phrase appears in 156(a)(5)(A)fromthe previous approvals.
Applicant is mistaken in its reading of 156(a)(5)(A). As previously explained by FDA in a
similar situation, FDA maintains that the phrase "provision of law" refers "to the statutory
provision under which the regulatory review occurs for a particular class of
products that is
eligible for patent term restoration, regardless of
whether that statutory provision is amended."
See U.S. PatentNo. 4,868,179, FDA letter of April
20, 2007 (2007 FDA letter) (copy attached
hereto). The FDA statedthete, and the USPTO concurs, thatthe phrase
is unambiguous on its
face. However, as explained in the 2007
FDA letter, even if the phrase is ambiguous, this
interpretation is permissible in light oflegislative intent, public policy concerns,
and applicable
case law. There is no suggestion in the legislative history thahe phrase
"first permitted
commercial marketing or use of the product under the provision of law under which such
regulatory review period occurred" as used in 156(a)(5)(A) is intended to treat amended
versions of section 505 as different provisions of law. Rather,
as explained by the FDA at page 6
of the 2007 FDA letter, to treat each different amended version
of section 505 as a different
provision of law would contravene the legislative intent of Congress by
allowing the term of
more than one patent to be extended if a product received more than one approval as a member
of a particular class of products. Furthermore, as Applicant acknowledges at p'ages 11-12 of their
u.s. Patent RE381 15
Page 5
PTE application and the FDA points out, at pages 8-9 of the 2007 FDA letter, the
only federal
cour decision to have addressed the question at issue, Westwood Pharms., Inc. v. Quigg" 1989
WL 205631,13 U.S.P.Q.2d2067 (D.D.C. 1989), supports the interpretation of
the FDA and the
USPTO. Finally, the Supreme Court
in Eli Lily and Co. v. Medtronic, Inc., 496 U.S. 661,667,
674,15 USPQ2d 1121, 1125-26, 1128 (1990), while making a distinction between the
term
"law" as broadly construed and a "provision oflaw," identified 21 U.S.C. 355 (the codification
of section 505), as the "provision" of
the FFDCA under which new drugs are subject to
premarket approval.
In view of the foregoing reasons, the term of the' 115 patent. is not eligible for extension under
156 basedupon the regulatory review period and approval of
the human drug product
NUEDEXTA( (dextromethorphan hydrobromide and quinidine sulfate). Thus, the application
for patent term extension is dismissed.
B. Conclusion
Because the approval ofNUEDEXTA( fails to comply with the requirement of section
156(a)(5)(A), the application for patent term extension under 35 U.S.C. 156(d)(1) is
dismissed.
Any correspondence with respect to this matter should be addressed as follows:
By mail: Mail Stop Hatch-Waxman PTE
Commissioner for Patents
P.O. Box 1450
Alexandria, VA 22313-1450
By FAX:
(571) 273-7755
Telephone inquiries related to this determination should be
directed to Mary C. Til
Senior Legal Advisor, at (571) 272-7755.
)j~_ edi
~
Senior Legal Advisor
Office of Patent Legal Addiinistration
cc: Offce of Regulatory Policy
Food and Drug Administration
10903 New Hampshire Ave., Bldg. 51, Rm. 6222
Silver Spring, MD 20993-0002
Re: NUEDEXTA(
( dextromethorphan
hydro bromide and quinidine
sulfate)
Docket No. FDA-2011-E-0269
Attention: Beverly Friedman
"~+".4...vlr~...&,.
( E
~'+.
""IIQ. . .
DEPARTMENT OF HEATH &. HUMA SERVICES
Public Health Service
APR 2 a 2007
Food and Drug Administation
Rockvile MD 20857
Re: BiDilcI
Doket No.: 2006E~0003
The Honorable Jon W. Dudas
Undersecretay of Commerce for Intellectu Propert and
Director of the United States Patent' and Trademark Offce
Mail Stop Hatch~ Waxan PTE
P.O. Box 1450
Alexandra, VA 22313-1450
Dear Director Dudas:
, Ths is in regard to the pplication for patent extension for US Patent No. 4,868,179 ('179
. patent), fied by Nitromed, Inc. under Title II of the Drug Price Competition and Patent Term
Restoration Act of 1984 (Public Law 98-417 codified at 35 U.S.C. 156) (Title II). The patent
clais a method of using the two active ingredients in the new drg BiDilCI: hydralazine
hydrochloride (hydralazine) and isosorbide dinitrate (ISDN). FDA approved BiDilcI for
'marketing on June 23,2005, under new drg application (NDA) 20-727.
A review of the Food and Drug Admnistration's official records indicates that BiDilOO was
subject to a regulatory review period under section 505 of the Federal Food, Drug, and Cosmetic
Act (FFDCA) before its commercial marketing or use. However, our review also indicates that
NDA 20-727 does not represent the first commercial marketing or use of either hydralazne or
ISDN. FDA has previously approved several new drgs containig these active ingredients. i
Under Title II, the term of a patent that claims a product, method of using a product, or a method
of manufactug a product can be extended. Ths extension is intended to compensate for
delayed market entry resulting from the reguatory review that must first occur for the product to
receive marketing approval. :ratent term restoration is, however, available only
"with the first
permtted commercial marketing or use of
the product under the provision a/law under which
such regulatory review period occured: . . ." (emphasis added) (the first commercial marketing
or use eligibilty requirement). For puroses of
patent term restoration, hydralazine and ISDN,
as active ingredients of a new drg, are each a "product."
, '
, FDA has received two sets of correspondence, dated November 4, 2005, and Februar 22, 2006,
from the law fi Fox Kiser, submitted on behalf of NitroMed. In this correspondence, Fox
Kiser assert that NitroMed may be eligible for patent term restoration even though FDA has
previously approved new drgs that contain hydrazine and ISDN. Essentially, Fox Kiser
argues that amending section 505 of the FFDCA would result in a new "provision of law" for
,~P-PJ'ovals ofNDAs for new drugs containing hydralaze occured prior to Title U'senactment in September
1984, including in i 982, i 983, and May i 984.NDAs have also been approved for other new drgs containing
hydrlaze and ISDN after enactment of Title II but prior to approval of BiD iI, in 1985, 1986, 1991 and 2001 for
hydralazie, and in 1981, 1988, 1991, 1993, 1995, 1998, 1999,2000 and 2005 for ISDN. ' .
puroses of patent term extension and that NitroMed should, therefore, be entitled to, a patent
term extension if BiDillI was the first new drug, containg either of th~se active ingredients to
be approved subsequent to any such amendment. .
We disagree. As explained more fully below, we view the term "provision of law" as referring to
the statutory provision under which the regulatory review occurs for a pariular class of.
products that is eligible for patent term restoration, regardless of whether that statutory provision
is amended. As indicated in section 156(g) of Title II, the "provision oflaw" for new drugs
would be section 505 of the FFDCA; For licensed biologics, it would be section 505 of the
FFDCA and section 351 of the Public Heath Service Act; for medical devices,lt would be
section 515 of the FFDCA; and for new anal drgs, it would be section 512 ofthe'FFDCA.
, 'Inclusion of the phrase "under the ,provision oflaw" limits the scope of the first commercial
marketing or use eligibilty requirement. Specifically, this phrase makes patent term restoration
available only in connection with the first permitted commercial marketing or use of a product as
a member of the class of products subject to regulatory review under that parcular sttutory
authnty. For example, only the first approval of an active ingredient for use in a new drg for .
hwnan u~e reviewed wider section 505 of the FFDCA would .be eligible, but patent temi
restoration could still be available for a patent in connection with review and approval under
section 512 of that same active ingredient for use in a new. anmal drg.
A. Relevant provisions of section 156.
Section 156(a) states, in pertinent par that:
The term of a patent which claims a product, a method of uS,ing a product, or a method of
,manufactug a product shall be extended in accordance with ths section from the
onginal expiration date of the patent. " . if-
'" '" '"
(4), the product has been subject to a regulatory review period before its commercial
marketig or use; (and)
(S)(A) . . . the pemiission for the commercial'marketing or use of
the product after such
reguatory review penod is. the first permitted commercial marketing or use of the
produt under the provision of law und,er wWch such reguatory review period occured;
For puroses of section 156, a "procluct" is: a food or color additive; medical device; or an active
ingredient of a new dig, biological product, new anmal drg, or vetennar biologicii product. 2
2 Section i
56(t)(1) defines "product" as a "drg product," medical device, food additive, or color additive. Section
. 156(f)(2) defines'''drg product" in pertinent par as:
. .. the active ingredient of--
(A) a new drg . . . human biological product (as those terms are used in the Federal Food, Drug, and Cosmetic
Act and the Public Health Service Act), or
(B) a new animal drg or veterinar ,biological product (as those terms are used in the Federal Food, Drug, and
2
Section 1 56(g)' defines the tenn '''regulatory review period," statingin pertinent par:
(g) For puroses of this
section, the tenn "regulatory review period" has the following
meanings:
(1)(A) In th~ case of a product which is a new drg . . . or hwnan biological product. . .
(B) The regulatory review period. . . is the sum of--
(i) the period beginnng on the date an exemption under'
subsection (i) of section 505 . . .
became effective for the approved product and ending on the date an application was
initially submitted for such drg product uider section 351 (or) 505 . . . , and
(ii) the period beginng on the date the application was initially ~ubmitted for the
approved product under section 351 (or) subsection (b) of section 505 . . . 'and ending on
the date such application was approved under such section.
(3)(A) In the case of a product which. is a medical device. . .
(B) The regulatory review period for a medical device is the sum of-~
(i)' the period beginnng on the date a clinical investigation on human involving the
device was begun and ending on the date an application was intially submitted with
respect to the device Under section 515, and
(ii) the period beging on the date an application was intially submitted with respect to
the device under section 515 and ending on the date such application was approved under
such Act or the peri~d beginng on the date a notice of completion of a product
development protocol was initially submitted under'section 515(f)(5) and ending on the
date the protocol was declared completed undersectioll 515(f)(6).
(4)(A) In the case ofa product which is a new anmal dr . ..
(B) Thedregulatory review period. . . is the sum of-~
(i) the period beginnng on, the earlier of the date a major health or environmental effects
test on the drug was initiated or the date an exemption.under subsection G) of section 512
became effective for the approved new anmal drug product and ending on the date an
application was initially'submitted for such anmal drg productunder section 512, and
(ii) the period. beging on the date the application was initially submitted for the '
Cosmetic Act and the Virus-Serum- Toxin Act) . . .
See a/so 37 CFR 1.71O(b); 21 CFR 60.3.
3
approved.an~al drg pro,du~t under subsectio? (b l 9f ~ection 5 1 ~ and en~ing on the date
such application was approved under such, section. .',
B~ FDA's Position.
FDA believes that the use of the terr "provision of law" in section 156 is facially unambiguous
and that the interpretation FDA and PTO have consistently applied to date must be applied: that
"the provision of law" refers to the statutory provision wider which the regulatory review occurs
for the class of products to wlch that statutory provision applies, regardless of how that
statutory provision may be amended. To the extent it might be argUed that section 156 is not
clear on its face, FDA 'and PTO's established interpretation is, nonetheless, permissible. Ths
interpretation comports with the legislative lstorY' by allowig only one patent term extension in
connection with the approval of an active ingredjent in a new drg under section 505 (or, more
broadly, in connection with the authonzation of any "product" as a member of a paricular class ,
of eligible products under the statutory provisi,on applicable to that p~icular class of products).
It also fuers equitable treatment of regulated ~ntities and fosters marketplace certnty by
providing a bnght line standard. Furer, the only cour to considetthis interpretative q'uestion
has endorsed FDA and PTO's established interpretation. See Westwood Pharmaceuticals, Inc. v.
Quigg, i 989 WL 205631, 13 USPQ2d 2067 (D.D.C. 1989). . .
1. The statute is, unambiguous.
Section 156(a) states that patent term restoration is available if the approval at issue is "the first
permitted commercial marketing or use of the product under the provision of law under which
such regulatory review period occured" (emphasis added). Section i 56(g) identifies the
statutory authorities ~dei which the reguatory review penod occursor vanous classes of
products for wlch patent term restoration is available. Specifically, section 156(g) reflects the
statutory provisions under wlch regulatory review occur: as section 505 of the FFDCA for
new drugs; as section 505 of the FFDCA and section 35 i of the Public Health Service Act for
licensed biologics; ~s section 515 of the FFDCA for medical devices; and as section 512 of the
-'FFDCA for new anmal drugs;
For the remaining classes of products eligible for patent term extension".food and color additives
and veterinary biological products--section 156(g) refers only to the statutes under which the '
regulatory review occurs--the FFDCA for food and ,color additives and the Virus-Seru- Toxin
Act for vetennary biological products. However, the implementig regulations for these
provisions of section 156(g)indicate the specific statutory provisions under which the regulatory
review occurs. See 9 CFR 124.2 (indicating that the provision oflaw for veterinar biological
products is section 102 of the Viru-Seru- Toxin Act); 21 CFR 60.3
(b)(6) (indicating that the
3 Setion I S6(1)( 4)(A) states that "Any reference to section 3 SL is a reference to section 3S1 of the Public Health.
Service Act." ,Section IS6(1)(4)(8) states that "any reference to section S03, SOS, S12, or 515 is a reference to
section S03, SOS; S12, or SiS of the Federal Food, Drug, and Cosmetic Act."
Section lS6(g) also defines "regulatory review period" for food ard color additives and for veterinary biological
products, referencing the FFDCA and the Virs-Serum-Toxins Act, respectively. without identifYing the
paricular provisions of these acts under which the regulatory review for these two classes of pro duet occurs.
4
provision of law for color additives is section 721 of the FFDCA); 21 CFR 60.3(b)(9) (indicating
that the provision of law for food additives is section 409 of the FFDCA).4 . , "
Nowhere, however, does section 156 (nor its. implementing regulations) 'suggest that amending'
any of these statutory authorities renders them new provisions oflaw under which patent term
extensions can be granted for products that have already undergone the regulatory review
applicable to that class of product. 5 Furer, a rule of statutory constrction support viewing a
general reference such as "the provision of law" as intend,ed to refer to the law on a subject
generally, including as that law might be amended.6
It seems unambiguous, therefore, that the term "the provision of lawlt is intended to mean the
statutory,authority under which regulatory review occurs for a specific class of products,
including any amendments tq that statutory authority. Under this interpretation, a patent
, 'extension is only granted the first time the product is approved for marketing as a member of that
specific class of products. For example, only one patent extension could be granted in
4 Contrary to Fox Kiser's suggestion, it is not only the numeric designation ofthe statutory provision thatis
control1ing, but also the class of product statutorily regulated. For example, Section 505 is a different "provision of
law" from Section 512 not only because the two have different numerical designations, but also because one, applies
to regulatory review of human drgs, while the other applies to regulatory review of animal drgs. See Eli Lily and
Co. v. Medtronic, Inc., 496 U.S. 661, 667, 674,15 USPQ2d i 121, i 125-26, 1128 (1990) (while making a distinction
between the term "law" as broadly constred and a "provision oflaw," identifying section 505 as a "provision" of
the FFDCA under which new drugs are subject to premarket approval).
5 Fox Kiser assert that a provjsion of the Patent and Trademark Offce's 'regulations support Fox Kiser's proposed,
contrar interpretation. Specifical1y, Fox Kiser argues that the reference to "the provision oflaw" in 37 CFR '
i. 740(a)(4) support its position that an amendment constitutes, a new provision oflaw. Section 1.740(a) states in
pertinent part: '
. . . A forial application for the extension of a' patent must include:
.. .,
(4) 'In the case of a drug
,product, an identification of each active ingredient in the product and as to each active'
ingredient, a statement that it has not been previously approved for commercial marketing or use under the
Federal Food, Drug. and Cosmetic Act, the Public Health Service Act, or the Virus-Seru-Toxin Act, or a
statement of when the active ingredient was approved for commercial marketing or use (either alone or in
combination with other active ingredients), the use for which it was approved, and the provision of law under
which it was approved. (emphasis added)
Contrary to Fox Kiser's assertion, the lie of "the provision of law" in section i ,740(a)(4) need not be interpreted as
indicating that amendments should be considered to produce new "provisions oflaw." Rather, section 1.740(a)(4) is
readily interpreted a,S'equiring applicants either: (I) to state that t~e active ingredients at issue have never been
approved for marketing under any of the statutes under which approval occurs for the classes of products eligible for
patent term restoration and, therefore, that none of those active ingredients has ever been eligible for patent term
restoration, or
(2) to identify any paricular provisions of law under which any of those active ingredients has
previously been approved, so that PTO can determine for which c~asses of products any of them have been approved
and are" therefore, no longer eligible for patent extension.
6 See Panama RR. Co, v. Johnson, 264 U.S. 3'75,391-92 (1924) ("generic reference" was "readily understood" as a
reference to the Employers' Liability ACt and its amendments); see also United States v, One Big'Six Wheel, 987
F.Supp. 169
(E.D,N.Y. 1997).
5
connection with pproval of an active ingredient for use in a new drg fo'r human use. However,
if, for example, that same active ingredient were subsequently approved for the fist time for use
in a new anmal drug, and a second patent claimed the active ingredient for that use, pate:it term ,
rest()ration c'ould be available for that second patent in connection with the anmal drg approval.
In short, inclusion of the term lithe provision of law" makes patent tern restoration available only
in connection with the first approval qf a product as a meipber of the class of products subject to
regulatory review under that paricular statutory provision. hic~usion of this term does not,serve
to make previously approved members of a class of products once agai eligible for patent term
extension,based upon whether the applicable statutory provision ha subsequently been amended.
, ,
2. The established interpretation comports with legislative intent to avoid
multiple patent term exten'sions for the same product.
,The legislative history for Title II relevant to this issue is limted. Nonetheless, it supports an
interpretation of "the provision oflawll that avoids,the same product's being eligible for multiple
patent term extensions. '
A'report considering an earlier version of section 156 that contaed the same "under the
provision of law . . ." languge U1timately encted in Title n, reflects,the House of
Representatives' Committee on the Judiciar's consideration, and rejection, of a proposal to grant
a patent term extension for each regulatory review period for a product, not just for the
regulatory review period associated with the first approval of the product. The report explai
that liThe net result" of this amenment would have been lito permt multiple patent term
extensions on what was essentially the sam"e drug product.
ii HR Rep No 98-857, pt 2, at 22
(1984), reprinted in 1984 USCCAN 2686, 7. The Commttee rejected the amendment on the
grounds that patents other than the first productpatent "frequentlyll do not represent lithe same
magntude ofinn~v~tion." H.R. Rep. No. 98-857, at 8. '
This same report describes the "under the provision of law" languge as permitting" an extension
if the approval. . . is the first . . . ofthat product under an applicable Federal law.'! HR Rep No
98-857, at 2706. It follows that, ,if a product had previously been approved under an applicable
Federal law, no additiona patent term restoration would be available, regardless of whether that
applicable Federal law were subsequently amended. .
FDA and PTO's established interpretation comports With this legislati\;e history because our
interpretation makes patent term restoration available oruy in connection with tlie first marketing
authorization for a product as a member of the class of products subject to review under the
paricular statutory authority. IIi,contrast, treating each amendment as generating a new
provision of law would be inconsistent with this legislative history, as such an interpretation
would make patent term extensions potentially available in connection with multiple approvals
of the same product.
6
3. The established interpretation prevents inequitable treatment of
applicants and
fosters marketplace certainty.
Granting a patent term extension to one product but not another due to the timing of an
amendment to the statutory authority under which the product is reviewed would be inequitable,1
and such a practice would undermine marketplace certinty. '
If, for example, applicant A has been granted a patent for a use of an active ingredient, and
applicant B has also been granted a patent for another use of the same active ingredient, we see
no sound policy grounds for makg one of these applicants, but not the other, eligible for patent
term restoration because of the timing of
a. legislative amendment. As the plain language
indicates and the legislative history reflects, we believe Congress intended to distinguish only
between the first approval and subsequent approvals of a product as a member of a paricular
class of regulated products, having judged that patents associated with'the first approval of a
product as a member of such ~ class likely reflect the most iriovative developments.
In addition, unlike Fox Kiser's proposed interpretation, the curent, long-standing interpretation
is straight-forward and predictable. It has resulted in litigation only once, over 17 years ago, and
the cour upheld our interpretation: In cnntrast, applying Fox Kiser's proposed interpretation
would produce 'marketplace uncertinty and spark additional litigation.
Most basically, if eligibilty for patent term restoration were dependent upon the timing of
statutory amendments, it would be impossible to predict with certty the availabilty of patent
term extensions for patents relating to subsequent applications for previously approved products.
Eligibilty would depend on whether an amendment happens to occur during the review of that
subsequent application and,whether that application then happns to be the first- approved
following that amendment. '
, ,
'Fox Kiser argues that circumstaces under which its interpretation would come into play would
arse rarely and affect few pharaceuticals. However, section 505 alone of the FFDCAhas, for.
example, been' amendd four times since enactment of Title II in 1984. The FFDCA has been
amended seventeen times over this same' time' period, and Congress regularly considers new bils
to amend the FFDCA. Under Fox Kiser's interpretation, patent term restoration might be '
available in coimection with approval of any previously approved product every time an
amendment occurs to the statutory authority under which a prior reguatory review occured for
that product.
1 Fox Kiser argues that failure to treat amendments to these statutory authorities as new provisions of law would
somehow unfairly har those applicants for whom regulatory review occurs after such an amendment. We
disagree. For example, if section 505 were' amended in such a maner. that the'time needed for regulatory review '
would increase (or decrease), the regulatory review period could expand (or contract) accordingly. See 35 USC
I 56(g)( I). As a consequence, an applicant eligible for patent term restoration after such an amendment could
receive a commensurately lengtened (or shortened) extension of its patent. In short, such amendments could affect
the length of the patent restoration, though not its availabilty, consistent with the apparent legislative intent for
section 156,
7
Furer, Fox Kiser's interpretation raises additional interpretive questions tht will serve only to
increase uncertinty and litigation. For example, Fox Kiser argues that only non-techncal '
modifications should trigger renewed ellgibilty for patent tenn restoration. Another applicant
might be expected to disagree. And this question is just one of many that could arse concernng
whether an amendment should be considered to have had a meangful effect on the reguhitory
review process. For example, it might be debated whether the amendment was made to a
relevant section of the statutory authority and, if so, whether the change: had a significant effect
on the review standards and/or tiing.8
4. The established interpretation has been upheld by the courts.
In WestwoodPhqrmaceuticals (1989 WI 205631), a district cour for the District of Columbia
Circuit addressed the precise interpretative question at issue here: whether an amendment of
section 505 ofthe FFDCA results in a new "provision oflaw" under which patent term
restoration becomes available again for an active ingredient previoui)lY apprved under section
505 prior to the amendment. The cour upheld FDA's determination that an amendment of
section 505 does not produce a new provision of law for puroses of patent tenn restoration
eligibiIity. "
, Fox Kiser argues thatthe cour gave undue deference to the agency's interpretation. It claims
that the cour should have applied the review stadard ariculated in Chevron u.s.A., Inc. v.
Natural Resources Defense Couni/, Inc., 461 U.S. 837 (1984).9 It argues that, 'in accordance
with that stadard, the cor should have: found that the statutory language unambiguously, ,
establishes that an amendment produces a new provision of law; given no deference to FDA's
contry interpretation as a result; and rued in favor of Westwood.
8 Another interpretative question. present~d by BDil and other previously approved ,hydralazine and ISDN products,
. might arse as follows: The regulatory review periods for BDil and other hydrlaze and ISDN products occured
subsequent to multiple amendments to section 505. The'egulatory review period for BiDil, for ex~ple, occtied
from April i; i 993, through, June 23, 2005. Consequently, this review spaned four amendments to section 505 (in
1997, 1999,2002, and 2003). Ths might raise the interpretive question fwhetheran applicant could be eligible for
multiple patent term extensions relating to the same appljcation if the application is the fist approved for that
product subsequent to multiple amendments to the statutory authority under which the review ofthat application
occiued. .
9 Under Chevron, when a cour is reviewing an agency's constrction of a statutory provision, the first step is to
detennine whether Congress has spoken to the precise question at ~ssue. To the extnt there exists any ambiguity in
the statutory language, the court must uphoid the agency's interpretation if that constrction is pennssible under the
statute; the court need not conclude that the agency's constrction was the only permissible one, or that the court
\yould have selected the same constrction. As detailed aboye, to the extent that the statutory language of section
i 56 is ambiguous, FDA and PTO's long-stading interpretation is clearly permissible; it is consistent with the
statutory language and comports with the legilative history, as well as fuhers sound policy'goals.
8
IUs tre that the cour deferred to 'the agency's inteipretati,on. However, Fox Kiser fails to note
that the cour also concluded that the agency's interpretation "is,consistent wjth the statutry
language and with the legislative history associated with ths provision." Westwood; 1989 WL
205631, "'3. In short, the only cour to address ths interpretive question expressly endorsed the
agency's statutory' constction.' '
C. Conclusion.
For all the reasons stated above, we conclude that an amendment made to section 505 of
the
FFDCA, or any other statutory authority under which regulatory review occurs for a class of
products eligible for patent term restoration; does not produce a new "provision of law" for
puroses of eligibilty for patent term res~oration under 35 USC 156. Therefore, since new drugs
'containg hydralaze and ISDN have previously been reviewed and approved by FDA under
section 505, BiDilGD is not eligible for patent term restoration.
Sincerely,
..~,a
~e -A. Axeira~
, Associate Director for Policy
Center for Drug Evaluation and'Research
ap.
cc: Diane Robertson, Fox' Kiser
,Matt Peterson, Fox Kiser
750 17th Street, N.W., Suite 1100
'Washington, DC 20006
Michael Sabolinski, M.D.
Senior Vice President
Clinical Development and Reguatory Affairs.
NitroMed, Inc.
125 Spring Street
, Lexington, MA 02421
9